Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.2941
Ziyi Zhu, Zhen Qian, Zhong-Qiang Qin, Bo Xie, Jianzhu Wei, Pei-pei Yang, Mu Yuan
BACKGROUND Subphrenic carcinoma has been identified as a significant risk factor for the thermal ablation of intrahepatic tumors, resulting in a high rate of residual tumor recurrence. Some studies have proposed that combination treatment with transarterial chemoembolization (TACE) followed by radiofrequency ablation is both feasible and safe for tumors in the subphrenic region. However, research specifically examining the therapeutic outcomes of combination therapy using TACE and microwave ablation (TACE-MWA) in subphrenic tumors is lacking. AIM To evaluate the efficacy and safety of TACE-MWA in patients with subphrenic hepatocellular carcinoma (HCC). METHODS Between December 2017 and December 2021, 49 patients diagnosed with HCC ≤ 6 cm, who received TACE-MWA, were included in this retrospective cohort study. These patients were classified into subphrenic and non-subphrenic groups based on the distance between the diaphragm and the tumor margin. The rates of local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Complications were evaluated by using a grading system developed by the Society of Interventional Radiology. RESULTS After a median follow-up time of 38 mo, there were no significant differences in LTP between the subphrenic and non-subphrenic groups (27.3% and 22.2% at 5 years, respectively; P = 0.66), PFS (55.5% at 5 years in both groups; P = 0.91), and OS (85.0% and 90.9% in the subphrenic and non-subphrenic groups at 5 years; P = 0.57). However, a significantly higher rate of LTP was observed in subphrenic HCC > 3 cm compared to those ≤ 3 cm (P = 0.085). The dosage of iodized oil [hazard ratio (HR): 1.52; 95% confidence interval (CI): 1.11-2.08; P = 0.009] and multiple tumors (HR: 13.22; 95%CI: 1.62-107.51; P = 0.016) were independent prognostic factors for LTP. There were no significant differences in complication rates between the two groups (P = 0.549). CONCLUSION Combined TACE and MWA was practical and safe for managing subphrenic HCC. The efficacy and safety levels did not vary significantly when tumors outside the subphrenic region were treated.
{"title":"Effectiveness and safety of sequential transarterial chemoembolization and microwave ablation for subphrenic hepatocellular carcinoma: A comprehensive evaluation","authors":"Ziyi Zhu, Zhen Qian, Zhong-Qiang Qin, Bo Xie, Jianzhu Wei, Pei-pei Yang, Mu Yuan","doi":"10.4251/wjgo.v16.i7.2941","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.2941","url":null,"abstract":"BACKGROUND\u0000 Subphrenic carcinoma has been identified as a significant risk factor for the thermal ablation of intrahepatic tumors, resulting in a high rate of residual tumor recurrence. Some studies have proposed that combination treatment with transarterial chemoembolization (TACE) followed by radiofrequency ablation is both feasible and safe for tumors in the subphrenic region. However, research specifically examining the therapeutic outcomes of combination therapy using TACE and microwave ablation (TACE-MWA) in subphrenic tumors is lacking.\u0000 AIM\u0000 To evaluate the efficacy and safety of TACE-MWA in patients with subphrenic hepatocellular carcinoma (HCC).\u0000 METHODS\u0000 Between December 2017 and December 2021, 49 patients diagnosed with HCC ≤ 6 cm, who received TACE-MWA, were included in this retrospective cohort study. These patients were classified into subphrenic and non-subphrenic groups based on the distance between the diaphragm and the tumor margin. The rates of local tumor progression (LTP), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Complications were evaluated by using a grading system developed by the Society of Interventional Radiology.\u0000 RESULTS\u0000 After a median follow-up time of 38 mo, there were no significant differences in LTP between the subphrenic and non-subphrenic groups (27.3% and 22.2% at 5 years, respectively; P = 0.66), PFS (55.5% at 5 years in both groups; P = 0.91), and OS (85.0% and 90.9% in the subphrenic and non-subphrenic groups at 5 years; P = 0.57). However, a significantly higher rate of LTP was observed in subphrenic HCC > 3 cm compared to those ≤ 3 cm (P = 0.085). The dosage of iodized oil [hazard ratio (HR): 1.52; 95% confidence interval (CI): 1.11-2.08; P = 0.009] and multiple tumors (HR: 13.22; 95%CI: 1.62-107.51; P = 0.016) were independent prognostic factors for LTP. There were no significant differences in complication rates between the two groups (P = 0.549).\u0000 CONCLUSION\u0000 Combined TACE and MWA was practical and safe for managing subphrenic HCC. The efficacy and safety levels did not vary significantly when tumors outside the subphrenic region were treated.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141646725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.
{"title":"Advances in immunotherapy of M2 macrophages and gastrointestinal stromal tumor","authors":"Xiao-Ke Wang, Xin Yang, Tong-Han Yao, Peng-Xian Tao, Guan-Jun Jia, De-Xian Sun, Lin Yi, Yuan-Hui Gu","doi":"10.4251/wjgo.v16.i7.2915","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.2915","url":null,"abstract":"Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.3158
Peng Zhou, Zihan Zheng, Tao Wan, Chuanwen Liao, Jie Wu
BACKGROUND Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. AIM To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. METHODS A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N’-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. RESULTS YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. CONCLUSION Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.
{"title":"Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis","authors":"Peng Zhou, Zihan Zheng, Tao Wan, Chuanwen Liao, Jie Wu","doi":"10.4251/wjgo.v16.i7.3158","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.3158","url":null,"abstract":"BACKGROUND\u0000 Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy.\u0000 AIM\u0000 To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG.\u0000 METHODS\u0000 A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N’-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay.\u0000 RESULTS\u0000 YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling.\u0000 CONCLUSION\u0000 Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.2902
A. Boilève, C. Smolenschi, A. Lambert, V. Boige, A. Tarabay, M. Valéry, A. Fuerea, T. Pudlarz, Thierry Conroy, A. Hollebecque, M. Ducreux
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS -mutated and KRAS -wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.
{"title":"Role of molecular biology in the management of pancreatic cancer","authors":"A. Boilève, C. Smolenschi, A. Lambert, V. Boige, A. Tarabay, M. Valéry, A. Fuerea, T. Pudlarz, Thierry Conroy, A. Hollebecque, M. Ducreux","doi":"10.4251/wjgo.v16.i7.2902","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.2902","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in patient management due to a dismal prognosis, increasing incidence, and limited treatment options. In this regard, precision medicine, which personalizes treatments based on tumour molecular characteristics, has gained great interest. However, its widespread implementation is not fully endorsed in current recommendations. This review explores key molecular alterations in PDAC, while emphasizing differences between KRAS -mutated and KRAS -wild-type tumours. It assesses the practical application of precision medicine in clinical settings and outlines potential future directions with respect to PDAC. Actionable molecular targets are examined with the aim of enhancing our understanding of PDAC molecular biology. Insights from this analysis may contribute to a more refined and personalized approach to pancreatic cancer treatment, ultimately improving patient outcomes.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.3357
Makiko Sasaki, T. Shimura, H. Nishie, Keita Kuroyanagi, T. Kanno, S. Fukusada, N. Sugimura, Yusuke Mizuno, Takayuki Nukui, Konomu Uno, Yuki Kojima, R. Nishigaki, Mamoru Tanaka, K. Ozeki, E. Kubota, Hiromi Kataoka
BACKGROUND BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment. CASE SUMMARY Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead. CONCLUSION This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
{"title":"BRAF K601E-mutated metastatic colorectal cancer in response to combination therapy with encorafenib, binimetinib, and cetuximab: A case report","authors":"Makiko Sasaki, T. Shimura, H. Nishie, Keita Kuroyanagi, T. Kanno, S. Fukusada, N. Sugimura, Yusuke Mizuno, Takayuki Nukui, Konomu Uno, Yuki Kojima, R. Nishigaki, Mamoru Tanaka, K. Ozeki, E. Kubota, Hiromi Kataoka","doi":"10.4251/wjgo.v16.i7.3357","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.3357","url":null,"abstract":"BACKGROUND\u0000 BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment.\u0000 CASE SUMMARY\u0000 Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.\u0000 CONCLUSION\u0000 This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.3069
Hao Li, Fei Li, Bo-Shen Wang, Bao-Li Zhu
BACKGROUND Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies. AIM To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker. METHODS This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning. RESULTS XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set. CONCLUSION Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.
{"title":"Prognostic significance of exportin-5 in hepatocellular carcinoma","authors":"Hao Li, Fei Li, Bo-Shen Wang, Bao-Li Zhu","doi":"10.4251/wjgo.v16.i7.3069","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.3069","url":null,"abstract":"BACKGROUND\u0000 Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. As liver cancer often presents no noticeable symptoms in its early stages, most patients are diagnosed at an advanced stage, complicating treatment. Therefore, the identification of new biomarkers is crucial for the early detection and treatment of HCC. Research on exportin-5 (XPO5) could offer new avenues for early diagnosis and improve treatment strategies.\u0000 AIM\u0000 To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.\u0000 METHODS\u0000 This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas, TIMER, and International Cancer Genome Consortium databases, correlating it with clinical profiles and disease progression. We performed in vitro experiments to examine the effect of XPO5 on liver cell growth. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology were used to elucidate the biological roles and signaling pathways. We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning.\u0000 RESULTS\u0000 XPO5 was significantly upregulated in HCC tissues, correlating with tumor grade, T-stage, and overall survival, indicating poor prognosis. Enrichment analyses linked high XPO5 expression with tumor immunity, particularly CD4 T cell memory activation and macrophage M0 infiltration. Drug sensitivity tests identified potential therapeutic agents such as MG-132, paclitaxel, and WH-4-023. Overexpression of XPO5 in HCC cells, compared to normal liver cells, was confirmed by western blotting and quantitative real-time polymerase chain reaction. The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis. Among the various machine learning algorithms, the C5.0 decision tree algorithm achieved accuracy rates of 95.5% in the training set and 92.0% in the validation set.\u0000 CONCLUSION\u0000 Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.2884
M. Chisthi
This editorial comments on the study by Ma et al , which delves into the efficacy and predictive factors associated with the combination of transarterial chemoembolization, lenvatinib, and programmed cell death protein-1 inhibition for the management of unresectable hepatocellular carcinoma. Analysing data from a retrospective study involving 102 patients, the treatment showcased a median overall survival (OS) of 26.43 months and a median progression-free survival (PFS) of 10.07 months. Notably, the objective response rate and disease control rate reached 61.76% and 81.37%, respectively. Specific factors such as Barcelona Clinic Liver Cancer (BCLC) Classification B-stage, early neutrophil-to-lymphocyte ratio response, and early alpha-fetoprotein response (> 20% decrease) correlated with superior OS and PFS. The triple therapy exhibited promising efficacy, particularly in BCLC B-stage disease, with prognostic markers aiding in patient stratification. Acknowledging the retrospective nature of the study design, future research should address this limitation and incorporate longer follow-up periods for a comprehensive evaluation of long-term outcomes.
{"title":"Effectiveness of transarterial chemoembolization in combination with lenvatinib and programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma","authors":"M. Chisthi","doi":"10.4251/wjgo.v16.i7.2884","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.2884","url":null,"abstract":"This editorial comments on the study by Ma et al , which delves into the efficacy and predictive factors associated with the combination of transarterial chemoembolization, lenvatinib, and programmed cell death protein-1 inhibition for the management of unresectable hepatocellular carcinoma. Analysing data from a retrospective study involving 102 patients, the treatment showcased a median overall survival (OS) of 26.43 months and a median progression-free survival (PFS) of 10.07 months. Notably, the objective response rate and disease control rate reached 61.76% and 81.37%, respectively. Specific factors such as Barcelona Clinic Liver Cancer (BCLC) Classification B-stage, early neutrophil-to-lymphocyte ratio response, and early alpha-fetoprotein response (> 20% decrease) correlated with superior OS and PFS. The triple therapy exhibited promising efficacy, particularly in BCLC B-stage disease, with prognostic markers aiding in patient stratification. Acknowledging the retrospective nature of the study design, future research should address this limitation and incorporate longer follow-up periods for a comprehensive evaluation of long-term outcomes.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC. AIM To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment. METHODS Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry. RESULTS Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC. CONCLUSION TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.
{"title":"Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma","authors":"Yuan Guo, Ru-Chun Li, Weiguo Xia, Xiong Yang, Wen-Bo Zhu, Fang-Ting Li, Hong-Tao Hu, Hai-Liang Li","doi":"10.4251/wjgo.v16.i7.3256","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.3256","url":null,"abstract":"BACKGROUND\u0000 The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC.\u0000 AIM\u0000 To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment.\u0000 METHODS\u0000 Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry.\u0000 RESULTS\u0000 Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC.\u0000 CONCLUSION\u0000 TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.3097
Xiang-yu Meng, Dong Yang, Bao Zhang, Tao Zhang, Zhi Zheng, Yan Zhao
BACKGROUND Gastric cancer (GC) is one of the most common malignancies worldwide. Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC. AIM To develop a glycolysis-based gene signature for prognostic evaluation in GC patients. METHODS Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data (STAD). A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis. The model was evaluated using the area under the receiver operating characteristic curves. RNA-sequencing data from high- and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis. Multiomics characteristics in different glycolysis status were also analyzed. RESULTS A five-gene signature comprising syndecan 2, versican, malic enzyme 1, pyruvate carboxylase and SRY-box transcription factor 9 was constructed. Patients were separated to high- or low-glycolysis groups according to risk scores. Overall survival of patients with high glycolysis was poorer. The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves. A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3- and 5-year overall survival. Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways, and low-glycolysis patients were related to Myc targets, oxidative phosphorylation, mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways. Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration. The patients with high glycolysis had lower tumor mutational burden and neoantigen load, higher incidence of microsatellite instability and lower chemosensitivity. High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis. CONCLUSION The genetic characteristics revealed by glycolysis could predict the prognosis of GC. High glycolysis significantly affects GC phenotype, but the detailed mechanism needs to be further studied.
{"title":"Glycolysis-related five-gene signature correlates with prognosis and immune infiltration in gastric cancer","authors":"Xiang-yu Meng, Dong Yang, Bao Zhang, Tao Zhang, Zhi Zheng, Yan Zhao","doi":"10.4251/wjgo.v16.i7.3097","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.3097","url":null,"abstract":"BACKGROUND\u0000 Gastric cancer (GC) is one of the most common malignancies worldwide. Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.\u0000 AIM\u0000 To develop a glycolysis-based gene signature for prognostic evaluation in GC patients.\u0000 METHODS\u0000 Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data (STAD). A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis. The model was evaluated using the area under the receiver operating characteristic curves. RNA-sequencing data from high- and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis. Multiomics characteristics in different glycolysis status were also analyzed.\u0000 RESULTS\u0000 A five-gene signature comprising syndecan 2, versican, malic enzyme 1, pyruvate carboxylase and SRY-box transcription factor 9 was constructed. Patients were separated to high- or low-glycolysis groups according to risk scores. Overall survival of patients with high glycolysis was poorer. The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves. A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3- and 5-year overall survival. Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways, and low-glycolysis patients were related to Myc targets, oxidative phosphorylation, mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways. Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration. The patients with high glycolysis had lower tumor mutational burden and neoantigen load, higher incidence of microsatellite instability and lower chemosensitivity. High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis.\u0000 CONCLUSION\u0000 The genetic characteristics revealed by glycolysis could predict the prognosis of GC. High glycolysis significantly affects GC phenotype, but the detailed mechanism needs to be further studied.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141647625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.4251/wjgo.v16.i7.2988
Peng Chen, Huan-Yu Wu
BACKGROUND Traditional Chinese medicine (TCM) is widely used as an important complementary and alternative healthcare system for cancer treatment in Asian countries. Network pharmacology, which utilizes various database platforms and computer software to study the interactions between complex drug components in vivo, is particularly useful for studying the pharmacodynamic mechanisms of multi-pathway and multi-target Chinese medicines. AIM To explore the potential targets and function of Jianpi Yiwei Recipe treatment of gastric cancer (GC) through network pharmacology and molecular docking. METHODS Data on the components of Jianpi Yiwei Recipe (Radix Astragali, Radix Codonopsis, Agrimonia eupatoria , Atractylodes macrocephala Koidz., Poria cocos , stir-baked rhizoma dioscoreae, Amomum villosum Lour., fried Fructus Aurantii, pericarpium citri reticulatae, Rhizoma Pinelliae Preparata, and Radix Glycyrrhizae Preparata) were collected and screened by using the TCM systems pharmacology database and analysis platform (TCMSP). Then the targets of these compounds were predicted. GC-related targets were screened using the GeneCards database. Venn diagram was used to identify common targets. An active ingredient-core target interaction network and a protein-protein interaction (PPI) network were built. Moreover, we performed gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the core targets and validated them by molecular docking. RESULTS TCMSP screening revealed 11 active components and 184 targets, whereas GeneCards found 10118 disease-related targets, with 180 shared targets between them. Topology analysis of the PPI network identified 38 targets, including ATK1, TP53, and tumor necrosis factor, as key targets for the treatment of GC by Jianpi Yiwei Recipe. Quercetin, naringenin, luteolin, etc. , may be the main active components of Jianpi Yiwei Recipe. GO enrichment analysis identified 2809, 1218, and 553 functions related to biological process, molecular function, and cellular component, respectively. KEGG pathway enrichment analysis revealed 167 related pathways, mainly involved in cancer, endocrine resistance, and AGE-RAGE signaling in diabetic complication. Validation with molecular docking analysis showed docking of key active components with core targets. CONCLUSION Jianpi Yiwei Recipe plays a therapeutic role in GC through multiple components, targets, and pathways. These findings form a basis for follow-up exploration of Jianpi Yiwei Recipe in the treatment of GC.
{"title":"Network pharmacology- and molecular docking-based exploration of the molecular mechanism underlying Jianpi Yiwei Recipe treatment of gastric cancer","authors":"Peng Chen, Huan-Yu Wu","doi":"10.4251/wjgo.v16.i7.2988","DOIUrl":"https://doi.org/10.4251/wjgo.v16.i7.2988","url":null,"abstract":"BACKGROUND\u0000 Traditional Chinese medicine (TCM) is widely used as an important complementary and alternative healthcare system for cancer treatment in Asian countries. Network pharmacology, which utilizes various database platforms and computer software to study the interactions between complex drug components in vivo, is particularly useful for studying the pharmacodynamic mechanisms of multi-pathway and multi-target Chinese medicines.\u0000 AIM\u0000 To explore the potential targets and function of Jianpi Yiwei Recipe treatment of gastric cancer (GC) through network pharmacology and molecular docking.\u0000 METHODS\u0000 Data on the components of Jianpi Yiwei Recipe (Radix Astragali, Radix Codonopsis, Agrimonia eupatoria , Atractylodes macrocephala Koidz., Poria cocos , stir-baked rhizoma dioscoreae, Amomum villosum Lour., fried Fructus Aurantii, pericarpium citri reticulatae, Rhizoma Pinelliae Preparata, and Radix Glycyrrhizae Preparata) were collected and screened by using the TCM systems pharmacology database and analysis platform (TCMSP). Then the targets of these compounds were predicted. GC-related targets were screened using the GeneCards database. Venn diagram was used to identify common targets. An active ingredient-core target interaction network and a protein-protein interaction (PPI) network were built. Moreover, we performed gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the core targets and validated them by molecular docking.\u0000 RESULTS\u0000 TCMSP screening revealed 11 active components and 184 targets, whereas GeneCards found 10118 disease-related targets, with 180 shared targets between them. Topology analysis of the PPI network identified 38 targets, including ATK1, TP53, and tumor necrosis factor, as key targets for the treatment of GC by Jianpi Yiwei Recipe. Quercetin, naringenin, luteolin, etc. , may be the main active components of Jianpi Yiwei Recipe. GO enrichment analysis identified 2809, 1218, and 553 functions related to biological process, molecular function, and cellular component, respectively. KEGG pathway enrichment analysis revealed 167 related pathways, mainly involved in cancer, endocrine resistance, and AGE-RAGE signaling in diabetic complication. Validation with molecular docking analysis showed docking of key active components with core targets.\u0000 CONCLUSION\u0000 Jianpi Yiwei Recipe plays a therapeutic role in GC through multiple components, targets, and pathways. These findings form a basis for follow-up exploration of Jianpi Yiwei Recipe in the treatment of GC.","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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