Objective: SOX11 is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of SOX11 in tumorgenesis.
Methods: SOX11 expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. SOX11's impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.
Results: SOX11 was significantly elevated in HCC tumors compared to controls. SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between SOX11 levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. SOX11 levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. SOX11 expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes. Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.
Conclusions: SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.
{"title":"<i>SOX11</i> as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.","authors":"Hongyu Chen, Qiangguo Ao, Yueling Wang, Yue Qian, Qingli Cheng, Wei Zhang","doi":"10.21147/j.issn.1000-9604.2024.04.03","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.03","url":null,"abstract":"<p><strong>Objective: </strong><i>SOX11</i> is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of <i>SOX11</i> in tumorgenesis.</p><p><strong>Methods: </strong><i>SOX11</i> expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. <i>SOX11</i>'s impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.</p><p><strong>Results: </strong><i>SOX11</i> was significantly elevated in HCC tumors compared to controls. <i>SOX11</i>-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between <i>SOX11</i> levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. <i>SOX11</i> levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. <i>SOX11</i> expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between <i>SOX11</i> and ferroptosis-associated genes. Decreased <i>SOX11</i> levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.</p><p><strong>Conclusions: </strong><i>SOX11</i> was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"378-397"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.21147/j.issn.1000-9604.2024.04.02
Ji Yeong An, Sung Eun Oh, Soomin Ahn, Hyoung-Ii Kim, Yoo Min Kim, Minah Cho, Keun Won Ryu, Hong Man Yoon, Young Kyu Park, In Gyu Kwon, Sung Hoon Noh, Kyung Hee Lee, In Cho, Myoung Won Son, Jong Won Kim, Young-Woo Kim
Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients.
Methods: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed.
Results: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests.
Conclusions: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.
{"title":"A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II<b>-</b>III gastric cancer patients.","authors":"Ji Yeong An, Sung Eun Oh, Soomin Ahn, Hyoung-Ii Kim, Yoo Min Kim, Minah Cho, Keun Won Ryu, Hong Man Yoon, Young Kyu Park, In Gyu Kwon, Sung Hoon Noh, Kyung Hee Lee, In Cho, Myoung Won Son, Jong Won Kim, Young-Woo Kim","doi":"10.21147/j.issn.1000-9604.2024.04.02","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.02","url":null,"abstract":"<p><strong>Objective: </strong>Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients.</p><p><strong>Methods: </strong>A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed.</p><p><strong>Results: </strong>The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests.</p><p><strong>Conclusions: </strong>This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"368-377"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.21147/j.issn.1000-9604.2024.04.05
Nan Chen, Minghe Zhao, Yunfeng Yao, Lin Wang, Yifan Peng, Tingting Sun, Tiancheng Zhan, Jun Zhao, Aiwen Wu
Objective: To evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) in mid-low locally advanced rectal cancer with negative mesorectal fascia (MRF).
Methods: This prospective, single-arm phase II trial was designed and conducted at Peking University Cancer Hospital. The patients who provided consent received 3 months of NCT (capecitabine and oxaliplatin, CapOX) followed by total mesorectal excision (TME). The primary endpoint was the rate of pathological complete response (pCR).
Results: From January 2019 through December 2021, a total of 53 patients were enrolled, 7.5% of whom experienced grade 3-4 adverse events during NCT. The pCR rate was 17.0% for the entire cohort, and the overall rate of postoperative complications was 37.7% (1.9% of grade IIIa patients). The 3-year disease-free survival rate was 91.4%, and 23.5% (12/51) of the patients suffered from major low anterior resection syndrome (LARS). Postoperative complications were independently associated with major LARS.
Conclusions: For patients with mid-low rectal cancer with negative MRF, 3 months of NCT were found to yield a favorable tumor response with acceptable toxicity. With fair long-term survival, the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.
目的评估新辅助化疗(NCT)对直肠系膜筋膜(MRF)阴性的中低位局部晚期直肠癌的安全性和有效性:这项前瞻性单臂 II 期试验由北京大学肿瘤医院设计和实施。征得同意的患者接受 3 个月的 NCT(卡培他滨和奥沙利铂,CapOX)治疗,然后进行全直肠系膜切除术(TME)。主要终点是病理完全反应率(pCR):从2019年1月到2021年12月,共有53名患者入组,其中7.5%的患者在NCT期间出现了3-4级不良事件。整个队列的病理完全反应率为17.0%,术后并发症总发生率为37.7%(IIIa级患者占1.9%)。3年无病生存率为91.4%,23.5%(12/51)的患者患有严重的低位前切除综合征(LARS)。术后并发症与严重低位前切除综合征密切相关:结论:对于MRF阴性的中低位直肠癌患者,3个月的NCT可产生良好的肿瘤反应,且毒性可接受。在长期生存率尚可的情况下,NCT疗法的围手术期并发症发生率低,肛门功能也可接受。
{"title":"Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia: Long-term outcomes of a prospective trial (PKUCH-R03 trial).","authors":"Nan Chen, Minghe Zhao, Yunfeng Yao, Lin Wang, Yifan Peng, Tingting Sun, Tiancheng Zhan, Jun Zhao, Aiwen Wu","doi":"10.21147/j.issn.1000-9604.2024.04.05","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.05","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) in mid-low locally advanced rectal cancer with negative mesorectal fascia (MRF).</p><p><strong>Methods: </strong>This prospective, single-arm phase II trial was designed and conducted at Peking University Cancer Hospital. The patients who provided consent received 3 months of NCT (capecitabine and oxaliplatin, CapOX) followed by total mesorectal excision (TME). The primary endpoint was the rate of pathological complete response (pCR).</p><p><strong>Results: </strong>From January 2019 through December 2021, a total of 53 patients were enrolled, 7.5% of whom experienced grade 3-4 adverse events during NCT. The pCR rate was 17.0% for the entire cohort, and the overall rate of postoperative complications was 37.7% (1.9% of grade IIIa patients). The 3-year disease-free survival rate was 91.4%, and 23.5% (12/51) of the patients suffered from major low anterior resection syndrome (LARS). Postoperative complications were independently associated with major LARS.</p><p><strong>Conclusions: </strong>For patients with mid-low rectal cancer with negative MRF, 3 months of NCT were found to yield a favorable tumor response with acceptable toxicity. With fair long-term survival, the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"410-420"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although there has been significant advancement in the identification and management of colorectal cancer (CRC) in recent years, there is still room for improvement in the current standard treatment regimen. One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care. Due to its dynamic, effective, and non-invasive benefits over tissue biopsy, the detection of minimal or molecular residual lesions (MRD) based on circulating tumor DNA (ctDNA) is beneficial to the clinical development of drugs for patients with CRC after radical treatment, as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution. The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions (upgrade or downgrade treatment) in CRC, stratify the risk of clinical recurrence more precisely, and predict the risk of recurrence in advance of imaging examination, according to a large number of observational or prospective clinical studies. With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA, which also improves the accuracy of clinical recurrence risk assessment for CRC. Therefore, it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized, stratified precision therapy; however, additional confirmation will require subsequent high-quality, prospective, large-scale randomized controlled studies. This article will provide an overview of the definition and clinical significance of MRD, the primary indications and technological challenges for MRD detection, along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.
{"title":"Potential value of detection of minimal residual disease in colorectal cancer following radical resection.","authors":"Wenji Pu, Fang Chen, Yuan Tang, Yanling Qu, Yunzhu Han, Jiandong Zha, Jing Jin, Fengming Kong","doi":"10.21147/j.issn.1000-9604.2024.04.07","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.07","url":null,"abstract":"<p><p>Although there has been significant advancement in the identification and management of colorectal cancer (CRC) in recent years, there is still room for improvement in the current standard treatment regimen. One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care. Due to its dynamic, effective, and non-invasive benefits over tissue biopsy, the detection of minimal or molecular residual lesions (MRD) based on circulating tumor DNA (ctDNA) is beneficial to the clinical development of drugs for patients with CRC after radical treatment, as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution. The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions (upgrade or downgrade treatment) in CRC, stratify the risk of clinical recurrence more precisely, and predict the risk of recurrence in advance of imaging examination, according to a large number of observational or prospective clinical studies. With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA, which also improves the accuracy of clinical recurrence risk assessment for CRC. Therefore, it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized, stratified precision therapy; however, additional confirmation will require subsequent high-quality, prospective, large-scale randomized controlled studies. This article will provide an overview of the definition and clinical significance of MRD, the primary indications and technological challenges for MRD detection, along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"442-454"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.21147/j.issn.1000-9604.2024.04.06
Dongsheng He, Rilan Bai, Naifei Chen, Jiuwei Cui
Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene, occurring in various tumor types. Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations, resistance to these inhibitors has eventually emerged. A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance. Immunotherapy has developed rapidly in recent years, and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations, finding that immune factors play an essential role in KRAS-mutant (KRAS-Mut) tumor therapy and targeted drug resistance. Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients. Here, we reviewed KRAS mutation-targeted treatment strategies and resistance issues, focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition. We aimed to guide innovative approaches combining RAS inhibition with immunotherapy, review advances in preclinical and clinical stages, and discuss challenges and future directions.
{"title":"Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors.","authors":"Dongsheng He, Rilan Bai, Naifei Chen, Jiuwei Cui","doi":"10.21147/j.issn.1000-9604.2024.04.06","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.06","url":null,"abstract":"<p><p>Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) is the most frequently mutated oncogene, occurring in various tumor types. Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations, resistance to these inhibitors has eventually emerged. A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance. Immunotherapy has developed rapidly in recent years, and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations, finding that immune factors play an essential role in KRAS-mutant (KRAS-Mut) tumor therapy and targeted drug resistance. Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients. Here, we reviewed KRAS mutation-targeted treatment strategies and resistance issues, focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition. We aimed to guide innovative approaches combining RAS inhibition with immunotherapy, review advances in preclinical and clinical stages, and discuss challenges and future directions.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"421-441"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated.
Methods: Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and in vitro experiments were then performed.
Results: DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.
Conclusions: Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.
目的:CD8+ T 细胞是抗肿瘤免疫反应的关键效应细胞:CD8+ T细胞是抗肿瘤免疫反应中的关键效应细胞。食管鳞状细胞癌(ESCC)中 CD8+ T 细胞浸润的机制尚未明确阐明:方法:收集新鲜的 ESCC 组织,并根据 CD8+ T 细胞的浸润密度进行分组。在对这些样本进行转录组测序并与癌症基因组图谱(The Cancer Genome Atlas,TCGA)ESCC数据进行综合分析后,筛选出一种分泌蛋白DEFB1,以探讨其在CD8+ T细胞浸润中的潜在作用。然后进行了生物信息学分析、组织学验证和体外实验:结果:DEFB1在ESCC中高表达,且DEFB1的高表达是总生存率的独立危险因素。由于 DEFB1 的上调或下调并不影响 ESCC 细胞的增殖、迁移和凋亡,我们推测 DEFB1 的致癌作用是通过调节微环境特征实现的。生物信息学分析表明,DEFB1可能在炎症反应和抗肿瘤免疫反应中扮演重要角色,并与ESCC中未成熟树突状细胞(imDC)的浸润相关。组织学分析进一步证实,在DEFB1高表达的ESCC样本中,CD8+ T细胞浸润较少,CD83+成熟树突状细胞(mDC)浸润较少,而CD1a+ imDC浸润较多。用重组DEFB1蛋白处理后,DC的成熟明显受阻,随后T细胞在体外二维和三维培养中的杀伤作用也受到影响:结论:肿瘤来源的DEFB1能抑制DC的成熟并削弱CD8+ T细胞的功能,是ESCC免疫耐受的原因。DEFB1在ESCC中的作用值得进一步探讨。
{"title":"Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma.","authors":"Jingjing Duan, Haotian Wang, Minglu Liu, Yin Chen, Ning Li, Jieqiong Liu, Lingxiong Wang, Lin Li, Yaru Liu, Pengfei Dong, Xiuxuan Wang, Zhongyi Fan, Shunchang Jiao","doi":"10.21147/j.issn.1000-9604.2024.04.01","DOIUrl":"10.21147/j.issn.1000-9604.2024.04.01","url":null,"abstract":"<p><strong>Objective: </strong>CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated.</p><p><strong>Methods: </strong>Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and <i>in vitro</i> experiments were then performed.</p><p><strong>Results: </strong>DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture <i>in vitro</i>.</p><p><strong>Conclusions: </strong>Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"351-367"},"PeriodicalIF":7.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30DOI: 10.21147/j.issn.1000-9604.2024.03.01
Liubo Chen, Hanguang Hu, Ying Yuan, Shanshan Weng
{"title":"CSCO guidelines for colorectal cancer version 2024: Updates and discussions.","authors":"Liubo Chen, Hanguang Hu, Ying Yuan, Shanshan Weng","doi":"10.21147/j.issn.1000-9604.2024.03.01","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.01","url":null,"abstract":"","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"233-239"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.
{"title":"Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.","authors":"Zhifei Li, Huan Zhao, Huihui Hu, Haili Shang, Yongjing Ren, Wenhui Qiu, Hao Su, Huifang Lyu, Xiaobing Chen","doi":"10.21147/j.issn.1000-9604.2024.03.07","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.07","url":null,"abstract":"<p><p>Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"306-321"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30DOI: 10.21147/j.issn.1000-9604.2024.03.09
Dechao Feng, Yuhan Xiao, Jie Wang, Ruicheng Wu, Zhouting Tuo, Koo Han Yoo, Wuran Wei, Dilinaer Wusiman, Zhipeng Wang, Dengxiong Li, Yubo Yang, William C Cho, Mang Ke
Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.
衰老与昼夜节律之间的联系已有几十年的历史,但它们之间的分子相互作用却一直不为人知,尤其是在癌症方面。在这种情况下,我们通过文献计量分析总结了该领域目前的研究现状和问题。我们检索了 PubMed 和 Web of Science 数据库中的文献。总体而言,癌症领域有关衰老和昼夜节律的论文数量呈上升趋势。来自美国、德国、意大利、中国和英国的研究人员的研究成果较多。发表论文最多的三个机构分别是加利福尼亚大学系统、法国研究型大学联盟(UDICE-French Research Universities)和德克萨斯大学系统。目前的研究热点包括氧化应激、乳腺癌、褪黑激素、细胞周期、卡路里限制、前列腺癌和 NF-KB。总之,文献计量分析的结果表明,许多方法都涉及癌症中衰老与昼夜节律之间复杂的相互作用。这些既有的和新兴的研究方向为我们探索癌症中衰老和昼夜节律的调控机制提供了指导,也为开发新的研究途径提供了参考。
{"title":"Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.","authors":"Dechao Feng, Yuhan Xiao, Jie Wang, Ruicheng Wu, Zhouting Tuo, Koo Han Yoo, Wuran Wei, Dilinaer Wusiman, Zhipeng Wang, Dengxiong Li, Yubo Yang, William C Cho, Mang Ke","doi":"10.21147/j.issn.1000-9604.2024.03.09","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.09","url":null,"abstract":"<p><p>Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"341-350"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-30DOI: 10.21147/j.issn.1000-9604.2024.03.05
Yifei Wang, Yidan Ma, Lei He, Jun Du, Xiaoguang Li, Peng Jiao, Xiaonan Wu, Xiaomao Xu, Wei Zhou, Li Yang, Jing Di, Changbin Zhu, Liming Xu, Tianlin Sun, Lin Li, Dongge Liu, Zheng Wang
Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.
Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed.
Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.
Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.
{"title":"Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.","authors":"Yifei Wang, Yidan Ma, Lei He, Jun Du, Xiaoguang Li, Peng Jiao, Xiaonan Wu, Xiaomao Xu, Wei Zhou, Li Yang, Jing Di, Changbin Zhu, Liming Xu, Tianlin Sun, Lin Li, Dongge Liu, Zheng Wang","doi":"10.21147/j.issn.1000-9604.2024.03.05","DOIUrl":"10.21147/j.issn.1000-9604.2024.03.05","url":null,"abstract":"<p><strong>Objective: </strong>The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.</p><p><strong>Methods: </strong>A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed.</p><p><strong>Results: </strong>Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, <i>MET</i> and <i>MYC</i> in epidermal growth factor receptor (<i>EGFR</i>)<i>/</i>anaplastic lymphoma kinase (<i>ALK</i>) mutant NSCLC, and more <i>PIK3CA</i> and <i>AURKA</i> in <i>EGFR/ALK</i> wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, <i>EGFR/ALK</i> wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.</p><p><strong>Conclusions: </strong>Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 3","pages":"282-297"},"PeriodicalIF":7.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}