Pub Date : 2025-08-30Epub Date: 2025-08-26DOI: 10.21037/jgo-2024-1006
Liming Xie, Qiuxing Yang, Wenjing Zhao, Guangzhi Lan, Guomei Tai
Background: Esophageal cancer (ESCA) is a prevalent malignancy with high morbidity and mortality. It has been demonstrated that lactylation, a novel post-translational modification, is linked to tumor progression and immunity. The objective of this study was to look into the potential role of lactylation-related genes in the prognosis and immune microenvironment of ESCA.
Methods: Lactylation-related prognostic genes (LRGs) in ESCA were screened using The Cancer Genome Atlas (TCGA) data. A consensus clustering analysis was conducted on the LRGs, and functional enrichment and immunoassays were performed for different clusters. We utilized least absolute shrinkage and selection operator (LASSO) and multivariate stepwise regression to develop a novel LRG prognostic signature. Subsequently, we assessed the performance of the signature through validation sets. Furthermore, we investigated the immune-related phenotypes of the signature and its response to treatment, as well as its sensitivity to drugs. Finally, experimental verification was performed through immunohistochemical (IHC) staining.
Results: We identified 29 LRGs associated with ESCA, and we classified ESCA patients into two lactylation clusters with different prognostic and immune infiltration patterns based on gene expression differences. A new prognostic signature consisting of three prognostic genes (NONO, H2BC18, POLDIP3) was constructed, demonstrating exceptional prediction accuracy in both internal and external datasets. Riskscores derived from this signature were independent prognostic factors for ESCA. Significant differences regarding clinical features, underlying functions, immune infiltration, reactions to immune therapy, and susceptibility to drugs were observed in the two riskscore groups. Finally, IHC staining confirmed the roles of these three genes in ESCA.
Conclusions: This study established a new ESCA prognostic signature composed of three lactylation-related genes, which can contribute to predicting prognosis and guiding clinical treatment.
{"title":"A novel lactylation-related signature for predicting esophageal cancer prognosis and immune infiltration.","authors":"Liming Xie, Qiuxing Yang, Wenjing Zhao, Guangzhi Lan, Guomei Tai","doi":"10.21037/jgo-2024-1006","DOIUrl":"10.21037/jgo-2024-1006","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (ESCA) is a prevalent malignancy with high morbidity and mortality. It has been demonstrated that lactylation, a novel post-translational modification, is linked to tumor progression and immunity. The objective of this study was to look into the potential role of lactylation-related genes in the prognosis and immune microenvironment of ESCA.</p><p><strong>Methods: </strong>Lactylation-related prognostic genes (LRGs) in ESCA were screened using The Cancer Genome Atlas (TCGA) data. A consensus clustering analysis was conducted on the LRGs, and functional enrichment and immunoassays were performed for different clusters. We utilized least absolute shrinkage and selection operator (LASSO) and multivariate stepwise regression to develop a novel LRG prognostic signature. Subsequently, we assessed the performance of the signature through validation sets. Furthermore, we investigated the immune-related phenotypes of the signature and its response to treatment, as well as its sensitivity to drugs. Finally, experimental verification was performed through immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>We identified 29 LRGs associated with ESCA, and we classified ESCA patients into two lactylation clusters with different prognostic and immune infiltration patterns based on gene expression differences. A new prognostic signature consisting of three prognostic genes (<i>NONO</i>, <i>H2BC18</i>, <i>POLDIP3</i>) was constructed, demonstrating exceptional prediction accuracy in both internal and external datasets. Riskscores derived from this signature were independent prognostic factors for ESCA. Significant differences regarding clinical features, underlying functions, immune infiltration, reactions to immune therapy, and susceptibility to drugs were observed in the two riskscore groups. Finally, IHC staining confirmed the roles of these three genes in ESCA.</p><p><strong>Conclusions: </strong>This study established a new ESCA prognostic signature composed of three lactylation-related genes, which can contribute to predicting prognosis and guiding clinical treatment.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1711-1735"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Multimodality treatment using chemotherapy, radiotherapy and surgery is standard practice for locally advanced esophageal squamous cell carcinoma (ESCC). Sarcopenia commonly occurs in patients with esophageal cancer. The effect of concurrent chemoradiotherapy (CCRT) on sarcopenia in patients with locally advanced ESCC remains unclear. We aimed to evaluate the effect of CCRT on sarcopenia in locally advanced ESCC.
Methods: This study included patients with locally advanced ESCC who received CCRT without surgery between 2011-2020. Sarcopenia was assessed using the skeletal muscle index (SMI) at the third lumbar vertebra (L3), which includes the psoas, paraspinal, and abdominal wall muscles, based on cross-sectional computed tomography (CT) scans before and after CCRT.
Results: In total, 213 patients with locally advanced ESCC who did not undergo esophagectomy after CCRT were included. Before CCRT, 178 patients (83.6%) had sarcopenia, while 35 patients (16.4%) did not. Moreover, 17 patients (48.6%) in the non-sarcopenia group developed sarcopenia after CCRT. The SMI significantly decreased after CCRT in both the sarcopenia and non-sarcopenia groups. The median overall survival (OS) was 12.6-15.7 months in all groups. The incidence of baseline sarcopenia showed no significant association with survival or CCRT-related toxicity. Male, high N-stage and decreasing body mass index (BMI) after CCRT were associated with poor survival prognosis.
Conclusions: Most patients with locally advanced ESCC had sarcopenia. Moreover, CCRT was associated with sarcopenia. Therefore, assessing sarcopenia before treatment and initiating interventions for prevention or treatment of sarcopenia may improve sarcopenia status.
{"title":"Sarcopenia following concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.","authors":"Thiranai Vongcharoenpol, Wongsakorn Chaochankit, Sakchai Ruangsin, Supparerk Laohawiriyakamol, Siriporn Leelakiatpaiboon, Natee Ina, Rungarun Kittichet, Patrapim Sunpaweravong, Somkiat Sunpaweravong","doi":"10.21037/jgo-2025-87","DOIUrl":"10.21037/jgo-2025-87","url":null,"abstract":"<p><strong>Background: </strong>Multimodality treatment using chemotherapy, radiotherapy and surgery is standard practice for locally advanced esophageal squamous cell carcinoma (ESCC). Sarcopenia commonly occurs in patients with esophageal cancer. The effect of concurrent chemoradiotherapy (CCRT) on sarcopenia in patients with locally advanced ESCC remains unclear. We aimed to evaluate the effect of CCRT on sarcopenia in locally advanced ESCC.</p><p><strong>Methods: </strong>This study included patients with locally advanced ESCC who received CCRT without surgery between 2011-2020. Sarcopenia was assessed using the skeletal muscle index (SMI) at the third lumbar vertebra (L3), which includes the psoas, paraspinal, and abdominal wall muscles, based on cross-sectional computed tomography (CT) scans before and after CCRT.</p><p><strong>Results: </strong>In total, 213 patients with locally advanced ESCC who did not undergo esophagectomy after CCRT were included. Before CCRT, 178 patients (83.6%) had sarcopenia, while 35 patients (16.4%) did not. Moreover, 17 patients (48.6%) in the non-sarcopenia group developed sarcopenia after CCRT. The SMI significantly decreased after CCRT in both the sarcopenia and non-sarcopenia groups. The median overall survival (OS) was 12.6-15.7 months in all groups. The incidence of baseline sarcopenia showed no significant association with survival or CCRT-related toxicity. Male, high N-stage and decreasing body mass index (BMI) after CCRT were associated with poor survival prognosis.</p><p><strong>Conclusions: </strong>Most patients with locally advanced ESCC had sarcopenia. Moreover, CCRT was associated with sarcopenia. Therefore, assessing sarcopenia before treatment and initiating interventions for prevention or treatment of sarcopenia may improve sarcopenia status.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1358-1365"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-25DOI: 10.21037/jgo-2025-111
Sara Wallam, Jimyung Park, Lawrence W Wu, Ryan H Moy
<p><strong>Background: </strong>Claudin18.2 (CLDN18.2), a tight junction molecule, is a novel therapeutic target for patients with advanced gastroesophageal adenocarcinoma. Recent phase III trials demonstrated improved survival with the addition of an anti-CLDN18.2 antibody (zolbetuximab) to first-line chemotherapy. However, expression of CLDN18.2 and its association with other biomarkers, especially in racial and ethnic minorities, remains poorly defined. We evaluated CLDN18.2 expression, its association with demographic and clinicopathologic characteristics, and its prognostic potential in a cohort of ethnically diverse patients.</p><p><strong>Methods: </strong>We conducted a single-center retrospective cohort study among patients with gastric, gastroesophageal, and esophageal adenocarcinoma in whom CLDN18.2 immunohistochemistry had been performed. Positivity was defined as moderate-to-strong expression in ≥75% of tumor cells. We extracted demographic and clinicopathologic data from the electronic medical record. Associations with CLDN18.2 were investigated using the <i>t</i>-test and Chi-squared test. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.</p><p><strong>Results: </strong>Among 75 evaluable patients, 32 (42.7%) were CLDN18.2 positive. Mean age was 66.2 years [standard deviation (SD), 13.2 years], 34.7% were female, and 62.7%, 18.7%, and 18.7%, had primary gastric, gastroesophageal junction, and esophageal tumors, respectively. At diagnosis, 32% were metastatic. The cohort was 49.3% White, 12% Black, 8% Asian, 21.3% other, and 9.3% unknown, and 20% identified as Hispanic. By ethnicity, 53.3% of Hispanic patients were CLDN18.2 positive compared to 38.2% of non-Hispanic patients. By race, 37.8% of White, 44.4% of Black, and 50% of Asian patients were CLDN18.2 positive. In univariate analyses, CLDN18.2 positivity was significantly associated with female sex (P=0.002) and human epidermal growth factor receptor 2 (HER2) negativity (P=0.03). <i>TP53</i> mutations were found in 65.2% of patients with available next-generation sequencing data, but there was no association with CLDN18.2 positivity. CLDN18.2 positivity was also not associated with disease-free survival in patients with localized or locally advanced disease, progression-free survival on first-line therapy in metastatic patients, or overall survival in the total population.</p><p><strong>Conclusions: </strong>This study provides new information on CLDN18.2 expression in an ethnically diverse population and suggests that Hispanic patients may have higher rates of CLDN18.2 positivity than non-Hispanic patients. We also demonstrate the association between CLDN18.2 and female sex and HER2 negativity and lack of association with survival, consistent with published data. Future research should further investigate differences in CLDN18.2 expression and identify subpopulations of patients who may benefit from CLDN18.2-targeted therapies.<
{"title":"Retrospective analysis of Claudin18.2 expression in ethnically diverse patients with gastroesophageal adenocarcinoma.","authors":"Sara Wallam, Jimyung Park, Lawrence W Wu, Ryan H Moy","doi":"10.21037/jgo-2025-111","DOIUrl":"10.21037/jgo-2025-111","url":null,"abstract":"<p><strong>Background: </strong>Claudin18.2 (CLDN18.2), a tight junction molecule, is a novel therapeutic target for patients with advanced gastroesophageal adenocarcinoma. Recent phase III trials demonstrated improved survival with the addition of an anti-CLDN18.2 antibody (zolbetuximab) to first-line chemotherapy. However, expression of CLDN18.2 and its association with other biomarkers, especially in racial and ethnic minorities, remains poorly defined. We evaluated CLDN18.2 expression, its association with demographic and clinicopathologic characteristics, and its prognostic potential in a cohort of ethnically diverse patients.</p><p><strong>Methods: </strong>We conducted a single-center retrospective cohort study among patients with gastric, gastroesophageal, and esophageal adenocarcinoma in whom CLDN18.2 immunohistochemistry had been performed. Positivity was defined as moderate-to-strong expression in ≥75% of tumor cells. We extracted demographic and clinicopathologic data from the electronic medical record. Associations with CLDN18.2 were investigated using the <i>t</i>-test and Chi-squared test. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.</p><p><strong>Results: </strong>Among 75 evaluable patients, 32 (42.7%) were CLDN18.2 positive. Mean age was 66.2 years [standard deviation (SD), 13.2 years], 34.7% were female, and 62.7%, 18.7%, and 18.7%, had primary gastric, gastroesophageal junction, and esophageal tumors, respectively. At diagnosis, 32% were metastatic. The cohort was 49.3% White, 12% Black, 8% Asian, 21.3% other, and 9.3% unknown, and 20% identified as Hispanic. By ethnicity, 53.3% of Hispanic patients were CLDN18.2 positive compared to 38.2% of non-Hispanic patients. By race, 37.8% of White, 44.4% of Black, and 50% of Asian patients were CLDN18.2 positive. In univariate analyses, CLDN18.2 positivity was significantly associated with female sex (P=0.002) and human epidermal growth factor receptor 2 (HER2) negativity (P=0.03). <i>TP53</i> mutations were found in 65.2% of patients with available next-generation sequencing data, but there was no association with CLDN18.2 positivity. CLDN18.2 positivity was also not associated with disease-free survival in patients with localized or locally advanced disease, progression-free survival on first-line therapy in metastatic patients, or overall survival in the total population.</p><p><strong>Conclusions: </strong>This study provides new information on CLDN18.2 expression in an ethnically diverse population and suggests that Hispanic patients may have higher rates of CLDN18.2 positivity than non-Hispanic patients. We also demonstrate the association between CLDN18.2 and female sex and HER2 negativity and lack of association with survival, consistent with published data. Future research should further investigate differences in CLDN18.2 expression and identify subpopulations of patients who may benefit from CLDN18.2-targeted therapies.<","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1420-1433"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-27DOI: 10.21037/jgo-2025-365
Feng Dai, Chunhan Pan, Chunyang Xu, Yu Yao, Mu Su, Jianwu Ren, Zhiyuan Qiu, Mario Capasso, Xiuming Zhang
Background: Portal hypertension (PHT) and hepatocellular carcinoma (HCC) often appear concurrently in clinic, and PHT variceal bleeding arising due to systemic treatment of HCC remains a clinical issue that urgently requires a solution. This study aimed to examine the therapeutic effects and clinical significance of transjugular intrahepatic portosystemic shunting (TIPS) in patients with HCC complicated with PHT.
Methods: In this retrospective study, 21 patients with HCC complicated with PHT who were admitted to The Second Hospital of Nanjing between June 2018 and June 2023 were included. TIPS was performed, and liver and kidney function, blood routine, and biochemical indicators such as ammonia were examined preoperatively, at 1 week postoperatively, and at 1 month postoperatively. To determine the improvements in stent blood flow, ascites, and esophageal and gastric varices, ultrasound and/or enhanced computed tomography were performed. Treatment was evaluated based on the Modified Solid Tumor Efficacy Evaluation Criteria. Parameters such as portal vein pressure and portal blood flow before and after TIPS were analyzed using paired-sample t-tests.
Results: Postoperatively, the direct pressure of the portal vein of patients decreased significantly from 28.33±7.15 to 19.27±3.10 mmHg (P<0.05). The amount of ascites also significantly decreased, whereas esophageal and gastric varicose veins significantly improved. Meanwhile, no significant differences were observed in liver or kidney function indicators, including bilirubin, transaminase, and creatinine, from the preoperative to the postoperative period.
Conclusions: TIPS can effectively improve the various symptoms of PHT without increasing the incidence of liver function damage or other complications in patients with HCC complicated with PHT.
{"title":"Clinical significance of transjugular intrahepatic portosystemic shunting for hepatocellular carcinoma complicated with portal hypertension.","authors":"Feng Dai, Chunhan Pan, Chunyang Xu, Yu Yao, Mu Su, Jianwu Ren, Zhiyuan Qiu, Mario Capasso, Xiuming Zhang","doi":"10.21037/jgo-2025-365","DOIUrl":"10.21037/jgo-2025-365","url":null,"abstract":"<p><strong>Background: </strong>Portal hypertension (PHT) and hepatocellular carcinoma (HCC) often appear concurrently in clinic, and PHT variceal bleeding arising due to systemic treatment of HCC remains a clinical issue that urgently requires a solution. This study aimed to examine the therapeutic effects and clinical significance of transjugular intrahepatic portosystemic shunting (TIPS) in patients with HCC complicated with PHT.</p><p><strong>Methods: </strong>In this retrospective study, 21 patients with HCC complicated with PHT who were admitted to The Second Hospital of Nanjing between June 2018 and June 2023 were included. TIPS was performed, and liver and kidney function, blood routine, and biochemical indicators such as ammonia were examined preoperatively, at 1 week postoperatively, and at 1 month postoperatively. To determine the improvements in stent blood flow, ascites, and esophageal and gastric varices, ultrasound and/or enhanced computed tomography were performed. Treatment was evaluated based on the Modified Solid Tumor Efficacy Evaluation Criteria. Parameters such as portal vein pressure and portal blood flow before and after TIPS were analyzed using paired-sample <i>t</i>-tests.</p><p><strong>Results: </strong>Postoperatively, the direct pressure of the portal vein of patients decreased significantly from 28.33±7.15 to 19.27±3.10 mmHg (P<0.05). The amount of ascites also significantly decreased, whereas esophageal and gastric varicose veins significantly improved. Meanwhile, no significant differences were observed in liver or kidney function indicators, including bilirubin, transaminase, and creatinine, from the preoperative to the postoperative period.</p><p><strong>Conclusions: </strong>TIPS can effectively improve the various symptoms of PHT without increasing the incidence of liver function damage or other complications in patients with HCC complicated with PHT.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1648-1657"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Neochlorogenic acid (NCA), a naturally occurring polyphenolic compound, exhibits diverse biological activities. This study aimed to investigate the inhibitory effects of NCA on hepatocellular carcinoma (HCC) cells and elucidate its underlying molecular mechanisms.
Methods: The anti-proliferative activity of NCA on human HCC cell lines HepG2 and Huh-7 was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Wound-healing assays were conducted to evaluate the effects of NCA on cell migration. Transcriptome sequencing was performed on NCA-treated and untreated Huh-7 cells to identify differentially expressed genes (DEGs) and signaling pathways. Western blot was used to validate the expression of key apoptosis-related proteins. In vivo experiments were carried out using a nude mouse xenograft model to assess the anti-tumor effects of NCA.
Results: NCA significantly inhibited the proliferation of HepG2 and Huh-7 cells, with half maximal inhibitory concentration (IC50) values of 345.5 and 231.8 µM at 24 hours, and 244.0 and 199.2 µM at 48 hours, respectively. Flow cytometry revealed that NCA induced apoptosis and G1 phase cell cycle arrest. Wound-healing assays demonstrated that NCA effectively suppressed HCC cell migration. Transcriptome analysis revealed 2,297 DEGs in NCA-treated Huh-7 cells (Padj<0.01), with 1,162 upregulated and 1,135 downregulated. Pathway enrichment analysis indicated significant enrichments in pathways related to "Alcoholism", "MicroRNAs in cancer", "Hepatocellular carcinoma", and "TGF-beta signaling pathway". Western blot confirmed the upregulation of pro-apoptotic proteins [BCL2-associated X protein (BAX); cysteinyl aspartate specific proteinase 3 (CASP3), BH3 interacting domain death agonist (BID), and cytochrome C (CYCS)] and downregulation of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). In vivo, NCA treatment significantly inhibited tumor growth.
Conclusions: This study provides compelling evidence that NCA inhibits HCC cell growth and migration both in vitro and in vivo through the induction of apoptosis and cell cycle arrest. Transcriptomic analysis reveals that NCA induces widespread changes in transcriptional networks and metabolic pathways within HCC cells, highlighting its potential as a promising therapeutic strategy for HCC.
{"title":"Mechanistic insights into the anti-tumor effects of neochlorogenic acid in hepatocellular carcinoma: <i>in vitro</i> and <i>in vivo</i> studies.","authors":"Menglong Xu, Yongchao Li, Wenqiang Sun, Haocheng Guan, Ruijun Shi, Shuwei Li","doi":"10.21037/jgo-2025-185","DOIUrl":"10.21037/jgo-2025-185","url":null,"abstract":"<p><strong>Background: </strong>Neochlorogenic acid (NCA), a naturally occurring polyphenolic compound, exhibits diverse biological activities. This study aimed to investigate the inhibitory effects of NCA on hepatocellular carcinoma (HCC) cells and elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>The anti-proliferative activity of NCA on human HCC cell lines HepG2 and Huh-7 was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Wound-healing assays were conducted to evaluate the effects of NCA on cell migration. Transcriptome sequencing was performed on NCA-treated and untreated Huh-7 cells to identify differentially expressed genes (DEGs) and signaling pathways. Western blot was used to validate the expression of key apoptosis-related proteins. <i>In vivo</i> experiments were carried out using a nude mouse xenograft model to assess the anti-tumor effects of NCA.</p><p><strong>Results: </strong>NCA significantly inhibited the proliferation of HepG2 and Huh-7 cells, with half maximal inhibitory concentration (IC<sub>50</sub>) values of 345.5 and 231.8 µM at 24 hours, and 244.0 and 199.2 µM at 48 hours, respectively. Flow cytometry revealed that NCA induced apoptosis and G1 phase cell cycle arrest. Wound-healing assays demonstrated that NCA effectively suppressed HCC cell migration. Transcriptome analysis revealed 2,297 DEGs in NCA-treated Huh-7 cells (Padj<0.01), with 1,162 upregulated and 1,135 downregulated. Pathway enrichment analysis indicated significant enrichments in pathways related to \"Alcoholism\", \"MicroRNAs in cancer\", \"Hepatocellular carcinoma\", and \"TGF-beta signaling pathway\". Western blot confirmed the upregulation of pro-apoptotic proteins [BCL2-associated X protein (BAX); cysteinyl aspartate specific proteinase 3 (CASP3), BH3 interacting domain death agonist (BID), and cytochrome C (CYCS)] and downregulation of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). <i>In vivo</i>, NCA treatment significantly inhibited tumor growth.</p><p><strong>Conclusions: </strong>This study provides compelling evidence that NCA inhibits HCC cell growth and migration both <i>in vitro</i> and <i>in vivo</i> through the induction of apoptosis and cell cycle arrest. Transcriptomic analysis reveals that NCA induces widespread changes in transcriptional networks and metabolic pathways within HCC cells, highlighting its potential as a promising therapeutic strategy for HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1699-1710"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-26DOI: 10.21037/jgo-2025-100
Ahmed Elhariri, Jaydeepbhai Patel, Himil Mahadevia, Karnav Modi, Douaa Albelal, Umair Majeed, Jeremy C Jones, Mitesh J Borad, Nguyen H Tran, Michael S Rutenberg, Hani Babiker
<p><strong>Background: </strong>The 5-year overall survival (OS) for stage IV pancreatic cancer is dismal despite aggressive systemic therapy. Stereotactic body radiation therapy (SBRT) involves delivering precise, highly conformal, and biologically effective doses of radiation via a linear accelerator to the tumor region. Clinical trials have shown improvement in OS and progression-free survival (PFS) with SBRT plus standard chemotherapy in oligometastatic (<5 metastatic lesions) solid tumors such as breast, lung, colorectal, and prostate cancers, when compared to chemotherapy alone. Factors predicting response to SBRT need to be further explored in oligometastatic pancreatic cancer (oPC). The study aims to assess the role of SBRT in the management of patients with oPC.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of oPC patients treated at the Mayo Clinic during the period from January 2012 to January 2022, who underwent SBRT to at least one site, including the primary site and/or sites of metastases, received at least 4 months of chemotherapy, and had a minimum of 1-year follow-up. Pertinent data were collected from the electronic health records after institutional review board (IRB) approval. The response rates (RRs) were assessed using the RECIST v1.1 criteria, and the PFS and OS were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to determine a statistically significant correlation between treatment and genomic characteristics with OS and PFS.</p><p><strong>Results: </strong>Sixty-one patients with oPC were identified, among whom 38% were female. Eighty-seven percent were Caucasian, and 13% were other ethnicities (African American, Hispanic, and Asian). The median age was 66 years. Patients received gemcitabine (gem) or 5-fluorouracil (5-FU) based chemotherapy. Eight-five percent of patients received chemotherapy within 3 months of SBRT and the median follow-up time of 16 months. The RR was 25% in the primary lesion and 17% in metastatic lesions. SBRT to primary pancreas lesion correlated with higher OS [hazard ratio (HR): 0.27, 95% confidence interval (CI): 0.082-0.89, P=0.03] but showed no difference in PFS (HR: 0.97, P=0.95) when compared to SBRT to any other metastatic site. SBRT to liver metastases had no improvement in OS (P=0.92) or PFS (P=0.70) versus SBRT to other metastatic sites. The type of chemotherapy (gem <i>vs</i>. 5-FU based) alongside SBRT within 3 months did not influence OS (P=0.47) or PFS (P=0.62) in these patients. Among 30 patients who underwent circulating tumor deoxyribonucleic acid (ctDNA) testing, <i>SMAD4</i> gene alteration correlated with significantly higher PFS (HR: 0.23, 95% CI: 0.065-0.87, P=0.03) but had no relation with OS (HR: 0.60, 95% CI: 0.18-2.03, P=0.41) compared to patients with undetectable <i>SMAD4</i> alteration.</p><p><strong>Conclusions: </strong>SBRT plus chemotherapy may have benefits in some patients with oPC. SBRT to primary panc
{"title":"Stereotactic body radiation therapy in oligometastatic pancreatic cancer: overall survival improvement and <i>SMAD4</i> as a predictor of progression-free survival.","authors":"Ahmed Elhariri, Jaydeepbhai Patel, Himil Mahadevia, Karnav Modi, Douaa Albelal, Umair Majeed, Jeremy C Jones, Mitesh J Borad, Nguyen H Tran, Michael S Rutenberg, Hani Babiker","doi":"10.21037/jgo-2025-100","DOIUrl":"10.21037/jgo-2025-100","url":null,"abstract":"<p><strong>Background: </strong>The 5-year overall survival (OS) for stage IV pancreatic cancer is dismal despite aggressive systemic therapy. Stereotactic body radiation therapy (SBRT) involves delivering precise, highly conformal, and biologically effective doses of radiation via a linear accelerator to the tumor region. Clinical trials have shown improvement in OS and progression-free survival (PFS) with SBRT plus standard chemotherapy in oligometastatic (<5 metastatic lesions) solid tumors such as breast, lung, colorectal, and prostate cancers, when compared to chemotherapy alone. Factors predicting response to SBRT need to be further explored in oligometastatic pancreatic cancer (oPC). The study aims to assess the role of SBRT in the management of patients with oPC.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of oPC patients treated at the Mayo Clinic during the period from January 2012 to January 2022, who underwent SBRT to at least one site, including the primary site and/or sites of metastases, received at least 4 months of chemotherapy, and had a minimum of 1-year follow-up. Pertinent data were collected from the electronic health records after institutional review board (IRB) approval. The response rates (RRs) were assessed using the RECIST v1.1 criteria, and the PFS and OS were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to determine a statistically significant correlation between treatment and genomic characteristics with OS and PFS.</p><p><strong>Results: </strong>Sixty-one patients with oPC were identified, among whom 38% were female. Eighty-seven percent were Caucasian, and 13% were other ethnicities (African American, Hispanic, and Asian). The median age was 66 years. Patients received gemcitabine (gem) or 5-fluorouracil (5-FU) based chemotherapy. Eight-five percent of patients received chemotherapy within 3 months of SBRT and the median follow-up time of 16 months. The RR was 25% in the primary lesion and 17% in metastatic lesions. SBRT to primary pancreas lesion correlated with higher OS [hazard ratio (HR): 0.27, 95% confidence interval (CI): 0.082-0.89, P=0.03] but showed no difference in PFS (HR: 0.97, P=0.95) when compared to SBRT to any other metastatic site. SBRT to liver metastases had no improvement in OS (P=0.92) or PFS (P=0.70) versus SBRT to other metastatic sites. The type of chemotherapy (gem <i>vs</i>. 5-FU based) alongside SBRT within 3 months did not influence OS (P=0.47) or PFS (P=0.62) in these patients. Among 30 patients who underwent circulating tumor deoxyribonucleic acid (ctDNA) testing, <i>SMAD4</i> gene alteration correlated with significantly higher PFS (HR: 0.23, 95% CI: 0.065-0.87, P=0.03) but had no relation with OS (HR: 0.60, 95% CI: 0.18-2.03, P=0.41) compared to patients with undetectable <i>SMAD4</i> alteration.</p><p><strong>Conclusions: </strong>SBRT plus chemotherapy may have benefits in some patients with oPC. SBRT to primary panc","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1658-1666"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-27DOI: 10.21037/jgo-2025-517
Quan Chen, Youtao Zhou, Zikai Lin, Cuiyan Yang, Hui Chen, Chuanfeng Ke
Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Despite recent advancements in screening strategies and treatments, the prognosis of CRC patients remains poor. Emerging evidences suggest that tumor immune microenvironment (TIME) and gut microbiota play a pivotal role in CRC progression and treatment. However, the clinical utility of these findings remains limited due to the absence of robust biomarkers. We sought to establish a clinically actionable tool that could guide personalized treatment decisions and ultimately improve outcomes for CRC patients.
Methods: We analyzed differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) and identified the prognostic genes for CRC by integrating the TIME- and gut microbiota-related genes from GeneCards. Using Mendelian randomization (MR), we examined the causal relationships between the prognostic genes, gut microbiota, and CRC. We then developed a risk model and independently validated its predictive performance using The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COADREAD) dataset as an external validation cohort.
Results: We established a risk model comprising the six identified genes and found that the high-risk group had a significantly higher mortality rate than the low-risk group. Additionally, the high-risk group showed increased immune cell infiltration and a diminished response to immunotherapy. The two-step MR analysis revealed that Deltaproteobacteria and Methanobrevibacter mediated the causal relationship between the prognostic genes and CRC. Further, the risk score was shown to be an independent prognostic factor for CRC survival, and the newly established nomogram demonstrated strong concordance between the predicted and observed clinical outcomes.
Conclusions: We developed a six-gene risk model and showed that gut microbes mediate the causal link between the prognostic genes and CRC. Further research on the regulation of the TIME and gut microbiota in CRC may provide valuable insights.
{"title":"Colorectal cancer prognosis: insights from the tumor immune microenvironment and gut microbiota.","authors":"Quan Chen, Youtao Zhou, Zikai Lin, Cuiyan Yang, Hui Chen, Chuanfeng Ke","doi":"10.21037/jgo-2025-517","DOIUrl":"10.21037/jgo-2025-517","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most common cancer worldwide. Despite recent advancements in screening strategies and treatments, the prognosis of CRC patients remains poor. Emerging evidences suggest that tumor immune microenvironment (TIME) and gut microbiota play a pivotal role in CRC progression and treatment. However, the clinical utility of these findings remains limited due to the absence of robust biomarkers. We sought to establish a clinically actionable tool that could guide personalized treatment decisions and ultimately improve outcomes for CRC patients.</p><p><strong>Methods: </strong>We analyzed differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) and identified the prognostic genes for CRC by integrating the TIME- and gut microbiota-related genes from GeneCards. Using Mendelian randomization (MR), we examined the causal relationships between the prognostic genes, gut microbiota, and CRC. We then developed a risk model and independently validated its predictive performance using The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COADREAD) dataset as an external validation cohort.</p><p><strong>Results: </strong>We established a risk model comprising the six identified genes and found that the high-risk group had a significantly higher mortality rate than the low-risk group. Additionally, the high-risk group showed increased immune cell infiltration and a diminished response to immunotherapy. The two-step MR analysis revealed that <i>Deltaproteobacteria</i> and <i>Methanobrevibacter</i> mediated the causal relationship between the prognostic genes and CRC. Further, the risk score was shown to be an independent prognostic factor for CRC survival, and the newly established nomogram demonstrated strong concordance between the predicted and observed clinical outcomes.</p><p><strong>Conclusions: </strong>We developed a six-gene risk model and showed that gut microbes mediate the causal link between the prognostic genes and CRC. Further research on the regulation of the TIME and gut microbiota in CRC may provide valuable insights.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1521-1533"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-27DOI: 10.21037/jgo-2024-1011
Xi Cheng, Jing Li, Yong Li, Fenghua Liu, Tiehua Li, Yan Meng, Miaomiao Wang
Background: Hepatocellular carcinoma (HCC) with adrenal metastasis is associated with poor prognosis and lacks standardized treatment strategies. Stereotactic body radiotherapy (SBRT) is a promising non-invasive option, yet its efficacy in this setting remains underexplored. This study aims to evaluate the efficacy and safety of SBRT in managing HCC patients with adrenal metastasis, focusing on factors influencing local control (LC) and overall survival (OS).
Methods: This retrospective study included 52 HCC patients with adrenal metastases treated with SBRT using the CyberKnife system between February 2016 and March 2022. Gross tumor volume (GTV) and biologically effective dose (BED) were calculated, and LC and OS were analyzed. Prognostic factors were assessed using univariate and multivariate Cox regression.
Results: At a median follow-up of 12.5 months, the overall response rate was 86.0%, with LC rates of 100%, 81.7%, and 75.8% at 6 months, 1 year, and 2 years, respectively. The median OS was 22 months. Intrahepatic tumor control and absence of extra-organ metastases were independently associated with improved OS (P=0.01 and P=0.001, respectively). No grade ≥2 adverse reactions were observed.
Conclusions: CyberKnife-based SBRT provides high LC rates and acceptable survival outcomes in HCC patients with adrenal metastases. Intrahepatic lesion control and extrahepatic disease burden are key factors influencing prognosis. SBRT should be considered as a local treatment strategy in multidisciplinary management of this population.
{"title":"Efficacy of stereotactic body radiotherapy in hepatocellular carcinoma with adrenal metastases: a retrospective analysis.","authors":"Xi Cheng, Jing Li, Yong Li, Fenghua Liu, Tiehua Li, Yan Meng, Miaomiao Wang","doi":"10.21037/jgo-2024-1011","DOIUrl":"10.21037/jgo-2024-1011","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) with adrenal metastasis is associated with poor prognosis and lacks standardized treatment strategies. Stereotactic body radiotherapy (SBRT) is a promising non-invasive option, yet its efficacy in this setting remains underexplored. This study aims to evaluate the efficacy and safety of SBRT in managing HCC patients with adrenal metastasis, focusing on factors influencing local control (LC) and overall survival (OS).</p><p><strong>Methods: </strong>This retrospective study included 52 HCC patients with adrenal metastases treated with SBRT using the CyberKnife system between February 2016 and March 2022. Gross tumor volume (GTV) and biologically effective dose (BED) were calculated, and LC and OS were analyzed. Prognostic factors were assessed using univariate and multivariate Cox regression.</p><p><strong>Results: </strong>At a median follow-up of 12.5 months, the overall response rate was 86.0%, with LC rates of 100%, 81.7%, and 75.8% at 6 months, 1 year, and 2 years, respectively. The median OS was 22 months. Intrahepatic tumor control and absence of extra-organ metastases were independently associated with improved OS (P=0.01 and P=0.001, respectively). No grade ≥2 adverse reactions were observed.</p><p><strong>Conclusions: </strong>CyberKnife-based SBRT provides high LC rates and acceptable survival outcomes in HCC patients with adrenal metastases. Intrahepatic lesion control and extrahepatic disease burden are key factors influencing prognosis. SBRT should be considered as a local treatment strategy in multidisciplinary management of this population.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1610-1621"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-26DOI: 10.21037/jgo-2025-503
Lijuan Xu, Wenli Dai, Li Chen, Lifeng Yao
<p><strong>Background: </strong>Colorectal cancer (CRC) is rising globally, with China bearing the highest burden. Fear of cancer recurrence (FCR) significantly impacts postoperative patients' well-being but remains understudied in China. The roles of illness perception, emotional distress, and social support in FCR are unclear. This study aims to assess FCR levels and identify influencing factors to guide early clinical intervention.</p><p><strong>Methods: </strong>From November 2023 to May 2024, a cross-sectional survey was conducted among 314 postoperative CRC patients at a tertiary cancer hospital in Shanghai. Eligible adults (≥18 years) with confirmed CRC who had completed primary treatment were recruited via convenience sampling. Validated questionnaires were completed independently or with staff assistance. These included the Fear of Cancer Recurrence Inventory (FCRI), the Brief Illness Perception Questionnaire (BIPQ), the Social Support Rating Scale (SSRS), the 15-Item Social Constraints Scale (SCS-15), and the Hospital Anxiety and Depression Scale (HADS). Pearson correlation analysis was conducted to examine associations among FCR, illness perception, social factors, and psychological symptoms. Subsequently, multivariable logistic regression was conducted to identify independent predictors of high FCR.</p><p><strong>Results: </strong>Of the 330 questionnaires distributed, 314 were deemed valid, yielding a response rate of 95.2%. The sample included 193 males (61.5%) and 121 females (38.5%), with a mean age of 59.7±12.3 years. Participants showed a high level of FCR, with a mean FCRI score of 69.64±27.10 and severity dimension score of 13.91±5.996. Univariate analysis revealed significant differences in age, monthly income, and residence between high and low-to-moderate FCR groups (P<0.05). The high FCR group had greater illness perception (BIPQ), higher social constraints (SCS-15), elevated anxiety and depression (P<0.001), and lower social support (SSRS; P=0.01) compared to the low-to-moderate group. Correlation analysis showed that FCR was significantly positively correlated with illness perception (r=0.548, P<0.01), social constraints (SCS-15; r=0.275, P<0.01), and psychological distress, including anxiety (r=0.596, P<0.01) and depression (r=0.426, P<0.01), highlighting the interplay among cognitive, social, and emotional factors. Subsequent binary logistic regression analysis identified illness perception and anxiety symptoms as significant independent predictors of FCR in patients with CRC.</p><p><strong>Conclusions: </strong>FCR is common among postoperative CRC patients and is strongly linked to illness perception and anxiety. These findings underscore the need for routine psychological screening and tailored communication. Interventions addressing maladaptive beliefs and emotional distress, along with integrated psychoeducational and psychosocial support, may enhance resilience and improve quality of life in survivorship care.</p
{"title":"Fear of cancer recurrence and associated factors in Chinese patients with colorectal cancer: a cross-sectional study.","authors":"Lijuan Xu, Wenli Dai, Li Chen, Lifeng Yao","doi":"10.21037/jgo-2025-503","DOIUrl":"10.21037/jgo-2025-503","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is rising globally, with China bearing the highest burden. Fear of cancer recurrence (FCR) significantly impacts postoperative patients' well-being but remains understudied in China. The roles of illness perception, emotional distress, and social support in FCR are unclear. This study aims to assess FCR levels and identify influencing factors to guide early clinical intervention.</p><p><strong>Methods: </strong>From November 2023 to May 2024, a cross-sectional survey was conducted among 314 postoperative CRC patients at a tertiary cancer hospital in Shanghai. Eligible adults (≥18 years) with confirmed CRC who had completed primary treatment were recruited via convenience sampling. Validated questionnaires were completed independently or with staff assistance. These included the Fear of Cancer Recurrence Inventory (FCRI), the Brief Illness Perception Questionnaire (BIPQ), the Social Support Rating Scale (SSRS), the 15-Item Social Constraints Scale (SCS-15), and the Hospital Anxiety and Depression Scale (HADS). Pearson correlation analysis was conducted to examine associations among FCR, illness perception, social factors, and psychological symptoms. Subsequently, multivariable logistic regression was conducted to identify independent predictors of high FCR.</p><p><strong>Results: </strong>Of the 330 questionnaires distributed, 314 were deemed valid, yielding a response rate of 95.2%. The sample included 193 males (61.5%) and 121 females (38.5%), with a mean age of 59.7±12.3 years. Participants showed a high level of FCR, with a mean FCRI score of 69.64±27.10 and severity dimension score of 13.91±5.996. Univariate analysis revealed significant differences in age, monthly income, and residence between high and low-to-moderate FCR groups (P<0.05). The high FCR group had greater illness perception (BIPQ), higher social constraints (SCS-15), elevated anxiety and depression (P<0.001), and lower social support (SSRS; P=0.01) compared to the low-to-moderate group. Correlation analysis showed that FCR was significantly positively correlated with illness perception (r=0.548, P<0.01), social constraints (SCS-15; r=0.275, P<0.01), and psychological distress, including anxiety (r=0.596, P<0.01) and depression (r=0.426, P<0.01), highlighting the interplay among cognitive, social, and emotional factors. Subsequent binary logistic regression analysis identified illness perception and anxiety symptoms as significant independent predictors of FCR in patients with CRC.</p><p><strong>Conclusions: </strong>FCR is common among postoperative CRC patients and is strongly linked to illness perception and anxiety. These findings underscore the need for routine psychological screening and tailored communication. Interventions addressing maladaptive beliefs and emotional distress, along with integrated psychoeducational and psychosocial support, may enhance resilience and improve quality of life in survivorship care.</p","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1534-1549"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30Epub Date: 2025-08-27DOI: 10.21037/jgo-2024-861
Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu
Background: Programmed cell death (PCD) pathways, including autophagy, ferroptosis, cuproptosis, neutrophil extracellular trap formation (NETosis), and paraptosis, are central to tumor biology and hold potential as therapeutic targets in colorectal cancer (CRC). The aim of this study is to use multi-omics data to analyze the role of PCD in CRC.
Methods: We conducted a multi-omics analysis using data from The Cancer Genome Atlas (TCGA), single-cell sequencing, and spatial transcriptomics to investigate the expression profiles, prognostic significance, and functional effects of PCD-associated genes in CRC. Key prognostic genes were identified through gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression modeling.
Results: Our analysis identified five PCD pathways with significant prognostic relevance in CRC, particularly autophagy and cuproptosis. Pan-cancer analyses highlighted unique and shared expression patterns of PCD-related genes across diverse cancer types, revealing their differential roles in cancer progression. Dynamic network biomarker (DNB) modeling pinpointed stage-specific critical transitions in PCD pathway activity, suggesting temporal variations in pathway influence on tumor progression. Functional assays demonstrated that overexpression of nuclear receptor coactivator 4 (NCOA4), an autophagy-related gene, suppressed CRC cell migration and invasion while promoting apoptosis, validating its anti-tumor role in CRC.
Conclusions: This study underscores the prognostic significance of PCD pathways in CRC, highlighting their potential as biomarkers and therapeutic targets. By identifying core genes within these pathways and elucidating their temporal effects on tumor progression, we provide a comprehensive foundation for future research into PCD-targeted therapies in CRC, aiming to enhance personalized treatment strategies.
{"title":"Identification of prognostic biomarkers in colorectal cancer through multi-omics profiling of programmed cell death pathways.","authors":"Song Qiao, Shangzhen Yang, Hua Hua, Chengtao Mao, Xiaolong Li, Cai Cheng, Hongguo Guo, Wanling Lu","doi":"10.21037/jgo-2024-861","DOIUrl":"10.21037/jgo-2024-861","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death (PCD) pathways, including autophagy, ferroptosis, cuproptosis, neutrophil extracellular trap formation (NETosis), and paraptosis, are central to tumor biology and hold potential as therapeutic targets in colorectal cancer (CRC). The aim of this study is to use multi-omics data to analyze the role of PCD in CRC.</p><p><strong>Methods: </strong>We conducted a multi-omics analysis using data from The Cancer Genome Atlas (TCGA), single-cell sequencing, and spatial transcriptomics to investigate the expression profiles, prognostic significance, and functional effects of PCD-associated genes in CRC. Key prognostic genes were identified through gene set variation analysis (GSVA), single-sample gene set enrichment analysis (ssGSEA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression modeling.</p><p><strong>Results: </strong>Our analysis identified five PCD pathways with significant prognostic relevance in CRC, particularly autophagy and cuproptosis. Pan-cancer analyses highlighted unique and shared expression patterns of PCD-related genes across diverse cancer types, revealing their differential roles in cancer progression. Dynamic network biomarker (DNB) modeling pinpointed stage-specific critical transitions in PCD pathway activity, suggesting temporal variations in pathway influence on tumor progression. Functional assays demonstrated that overexpression of nuclear receptor coactivator 4 (<i>NCOA4</i>), an autophagy-related gene, suppressed CRC cell migration and invasion while promoting apoptosis, validating its anti-tumor role in CRC.</p><p><strong>Conclusions: </strong>This study underscores the prognostic significance of PCD pathways in CRC, highlighting their potential as biomarkers and therapeutic targets. By identifying core genes within these pathways and elucidating their temporal effects on tumor progression, we provide a comprehensive foundation for future research into PCD-targeted therapies in CRC, aiming to enhance personalized treatment strategies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1503-1520"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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