Journal of gastrointestinal oncology最新文献

{"title":"Genetically proxied risk and protective factors for pancreatic cancer: a systematic review and meta-analysis of Mendelian randomization studies.","authors":"Fada Luo, Weicheng Mou, Yong Zeng, Xingwei Ouyang, Richard J Bold, Somashekar G Krishna, Atsushi Yamaguchi, Li Zhang","doi":"10.21037/jgo-2025-305","DOIUrl":"10.21037/jgo-2025-305","url":null,"abstract":"<p><strong>Background: </strong>Despite extensive observational evidence implicating lifestyle habits, metabolic factors, hormone levels, predisposing genetic conditions, medications, and other exposures, causal inference regarding pancreatic ductal adenocarcinoma (PDAC) risk factors remain contentious due to residual confounding. This Mendelian randomization (MR) meta-analysis was employed to address unresolved etiological controversies and systematically investigate causal relationships between these modifiable factors and clinical outcomes.</p><p><strong>Methods: </strong>We conducted a systematic assessment and meta-analysis focusing on studies that employed MR methods to assess the correlation between impact factors and PDAC. We searched five databases, including PubMed, Embase, Web of Science, Scopus, and Ovid, and ultimately included 82 studies, with 292 independent findings. A meta-analysis was performed on 56 of these influencing factors.</p><p><strong>Results: </strong>Our study found that several factors may be risk factors for PDAC, including body mass index (BMI) [odds ratio (OR): 1.23, 95% confidence interval (CI): 1.10-1.36], gut microbiota (OR: 1.25, 95% CI: 1.05-1.49), diabetes mellitus (OR: 1.07, 95% CI: 1.02-1.13), body size (OR: 1.72, 95% CI: 1.48-2.00), fasting insulin (OR: 2.23, 95% CI: 1.61-3.09), hip circumference (OR: 1.34, 95% CI: 1.11-1.61) and inflammatory bowel disease (IBD) (OR: 1.18, 95% CI: 1.04-1.34). Conversely, potential protective factors against PDAC included lycopene intake (OR: 0.87, 95% CI: 0.77-0.99) and cathepsin E levels (OR: 0.96, 95% CI: 0.94-0.99), and these factors should be further investigated.</p><p><strong>Conclusions: </strong>This meta-analysis of MR studies identified several risk and protective factors for pancreatic cancer, with most showing low heterogeneity. However, these findings represent associations, not causality. These findings may inform clinical risk assessment while awaiting further validation. The study highlights the need for continued research focusing on diverse populations, mechanistic studies, longitudinal investigations, and translational work to advance understanding and develop effective strategies for pancreatic cancer prevention and treatment.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"1233-1247"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649611","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}

{"title":"Camrelizumab plus sorafenib or apatinib achieved long-term survival in a patient with hepatocellular carcinoma and an Eastern Cooperative Oncology Group performance status of 3: a case report.","authors":"Xin Wang, Guangbin Ji, Xi Chen, Hongbo Hu, Lianyue Zou, Haruhiko Takeda, Caiyun Zhou","doi":"10.21037/jgo-2025-433","DOIUrl":"10.21037/jgo-2025-433","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a global health burden, with limited therapeutic options for patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS). Current guidelines recommend best supportive care (BSC) for patients with HCC and an ECOG PS ≥3, as systemic therapies such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) are typically restricted to PS 0-1 population. To our knowledge, this may be the first reported case suggesting that targeted therapy combined with ICIs could be feasible and potentially beneficial in a patient with HCC and an ECOG PS of 3.</p><p><strong>Case description: </strong>A 47-year-old male with hepatitis B-related HCC presented in August 2018 with an 80 mm × 69 mm right hepatic lobe tumor, an ECOG PS of 2, and Child-Pugh class A. He underwent curative resection and adjuvant transcatheter arterial chemoembolization (TACE). In December 2020, recurrence was noted with the tumor lesion measuring 130 mm × 120 mm with accompanying portal vein cancer thrombosis. His ECOG PS was 3 (bedridden >50% of the day), the alpha fetoprotein (AFP) level was >1,000 IU/mL, and the cancer antigen 125 (CA125) level was 118 U/mL. Despite contraindications, sorafenib was initiated but failed to improve symptoms or tumor markers. In February 2021, camrelizumab (21-day cycles) was added to ongoing sorafenib. By May 2021, the ECOG PS improved to 1, and he experienced partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and the tumor had shrunk to 87 mm × 64 mm. AFP normalized to 1.63 IU/mL by September 2023. Sorafenib was replaced with apatinib in February 2023 due to rash, but PR was maintained. At the follow-up in March 2025, the patient was alive with a 49-month progression-free survival (PFS) from camrelizumab initiation, stable disease (49 mm × 40 mm), and normal AFP and CA125 levels. Key baseline biomarkers included a neutrophil-to-lymphocyte ratio (NLR) of 3.67 and an albumin-bilirubin (ALBI) grade of 1. Treatment adherence was complicated by financial interruptions but resumed with a combination of apatinib plus camrelizumab.</p><p><strong>Conclusions: </strong>This case may provide preliminary support for the potential use of targeted therapy combined with immune checkpoint inhibitors in patients with HCC and an ECOG performance status of 3.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"1314-1320"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649619","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}

{"title":"PANoptosis-associated genes exhibit significant potential in the diagnosis of hepatocellular carcinoma.","authors":"Yujin Li, Junfeng Li, Yu Chen","doi":"10.21037/jgo-2025-356","DOIUrl":"10.21037/jgo-2025-356","url":null,"abstract":"<p><strong>Background: </strong>To date, little research has been conducted on whether PANoptosis-related genes can be used to predict the prognosis of hepatocellular carcinoma (HCC), despite their effect on several biological processes in cancer. This study sought to establish a dependable gene signature related to PANoptosis that can identify various HCC subtypes and predict their outcomes.</p><p><strong>Methods: </strong>A dataset containing RNA sequencing and clinical information was obtained from The Cancer Genome Atlas (TCGA) database. Important PANoptosis-related HCC genes were selected for the bioinformatic analysis. The HCC tumors were classified by a consistent cluster analysis, and the prognosis was studied in connection with a PANoptosis-related HCC model.</p><p><strong>Results: </strong>The univariate Cox analysis of TCGA-HCC data identified 4,354 genes linked to patient prognosis. The Venn diagram intersection analysis showed that 95 genes were associated with PANoptosis. Using consensus clustering, TCGA-HCC patients were categorized into two subtypes based on these 95 genes, and a stability analysis and principal component analysis (PCA) confirmed significant subtype differences. The low-risk subtype had significantly better overall survival (OS) than the high-risk subtype. The Gene Ontology (GO) analysis of the genes in the high-risk cluster 1 (C1) group revealed that the upregulated genes were associated with mitosis, chromosome segregation, and cell cycle checkpoints, while the downregulated genes were associated with alcohol and steroid metabolism pathways. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the upregulated genes were involved in the cell cycle and DNA replication pathways, while the downregulated genes were mainly involved in drug metabolism and chemical carcinogenesis. The least absolute shrinkage and selection operator (LASSO) and Cox regression analyses of the 95 PANoptosis-related genes identified 36 prognostic markers. Patients were then allocated to low- and high-risk groups, and the low-risk group had significantly better OS than the high-risk group. The prognostic accuracy of the model was validated by a receiver operating characteristic (ROC) curve analysis, yielding area under the curve (AUC) values of 0.826, 0.865, and 0.854 for 1-, 3-, and 5-year survival, respectively.</p><p><strong>Conclusions: </strong>PANoptosis-related genes are strongly associated with tumor classification in HCC. The PANoptosis-related gene signatures showed robust performance in predicting HCC prognosis, and thus could be used as new approaches for HCC diagnosis and therapy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"1105-1114"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649647","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}

{"title":"<i>TRIP6/c-Fos</i> regulating <i>GPX4</i> modulates gastric cancer growth by inhibiting ferroptosis.","authors":"Yang Huang, Wentao Zhang, Jilong Shen, Yongxiang Li","doi":"10.21037/jgo-22-1178","DOIUrl":"10.21037/jgo-22-1178","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a digestive system tumor with the highest incidence in China. In recent years, the role of ferroptosis in tumor occurrence and development has received more and more attention. In this study, we sought to identify the genes related to ferroptosis in GC and explain the mechanism of these related genes.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) database was analyzed using bioinformatics technology to identify the gene closely related to ferroptosis [i.e., thyroid hormone receptor interacting protein 6 (<i>TRIP6</i>)]. We then constructed the knockdown and overexpression of <i>TRIP6</i> cell lines to verify the effects of <i>TRIP6</i> on cell proliferation and ferroptosis using quantitative polymerase chain reaction (qPCR), western blot, co-immunoprecipitation (CO-IP), flow analysis, dual-luciferase report, and other technologies. We also validated the results by ferroptosis inducers and inhibitors.</p><p><strong>Results: </strong>The bioinformatics analysis showed that ferroptosis is closely related to <i>TRIP6</i>. <i>TRIP6</i> is highly expressed in GC cells and tissues and is associated with a poor prognosis. The knockdown or overexpression of <i>TRIP6</i> affects cell proliferation and ferroptosis, which we verified via recovery experiments with ferroptosis activators and inhibitors. <i>TRIP6</i> also affected the expression of glutathione (GSH) peroxidase 4 (<i>GPX4</i>). The CO-IP and silver staining experiments verified that <i>TRIP6</i> can bind to the transcription factor <i>c-Fos</i> and stabilize its expression. The dual-luciferase experiment confirmed that the transcription factor <i>c-Fos</i> regulated the expression of <i>GPX4</i>.</p><p><strong>Conclusions: </strong><i>TRIP6</i>, which is highly expressed in GC, binds to and stabilizes the expression of <i>c-Fos</i>, which acts as a transcription factor to regulate the expression of <i>GPX4</i> and thereby inhibit cell ferroptosis.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"840-852"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649524","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}

{"title":"Impact of cancer-directed surgery for gastric cancer patients with lung metastasis: a prognosis analysis.","authors":"Zhongyu Tan, Xiyao Du, Mo Zeng, Yingli Huang, Yunlong Cai, Shanshan Huang","doi":"10.21037/jgo-2024-976","DOIUrl":"10.21037/jgo-2024-976","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is acknowledged as a fatal malignant disease. The impact of cancer-directed surgery (CDS) on the prognosis of patients with lung metastatic gastric cancer (LMGC) was investigated in this study.</p><p><strong>Methods: </strong>The clinical data of LMGC patients after CDS were obtained from the Surveillance, Epidemiology, and End Results (SEER) database [2000-2020]. This study used the R software to perform propensity score matching (PSM). Then, the influence of different variables on overall survival (OS) was measured by Cox regression analysis and Kaplan-Meier curve analysis.</p><p><strong>Results: </strong>A total of 1,045 LMGC patients were included in the present study. Among these patients, 970 (92.82%) patients were assigned to the non-CDS group and 75 (7.18%) were assigned to the CDS group. After PSM, 165 (72.37%) patients in the non-CDS group and 63 (27.63%) patients in the CDS group were identified. The Kaplan-Meier analysis results revealed that the median OS was significantly longer in the CDS group (12 <i>vs.</i> 6 months, P=0.03). Furthermore, the multivariate Cox regression analysis after PSM indicated that chemotherapy [hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.30-0.40, P<0.001] and CDS (HR =0.50, 95% CI: 0.38-0.67, P<0.001) were associated to favorable OS for LMGC patients.</p><p><strong>Conclusions: </strong>CDS may improve the prognosis of patients with LMGC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"890-898"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649614","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}

{"title":"Impact of occlusal support on postoperative complications in patients with colorectal cancer resections.","authors":"Masano Sagawa, Hajime Yokomizo, Sachiyo Okayama, Shunsuke Iwamoto, Ryohei Nishiguchi, Shinichi Asaka, Takebumi Usui, Takeshi Shimakawa, Hisashi Yano, Sayaka Yoshiba, Shunichi Shiozawa","doi":"10.21037/jgo-2024-1013","DOIUrl":"10.21037/jgo-2024-1013","url":null,"abstract":"<p><strong>Background: </strong>Although poor oral health has been associated with longer hospital stays and higher medical costs, no studies have specifically examined the relationship between preoperative dental status and postoperative complications in patients undergoing gastrointestinal cancer surgery. The objective of this study was to evaluate the occlusal support range in patients aged 65 years and older in relation to inpatient dietary habits and postoperative outcomes, and to determine whether decreased occlusal support is a factor influencing postoperative infectious complications.</p><p><strong>Methods: </strong>In total, 169 patients, aged 65 years or older and undergoing colorectal cancer resection, were included. Preoperatively, dentists assessed occlusal support using the Eichner index (EI). Based on the EI classification, dietitians, a speech-language-hearing therapist, and nurses collaboratively selected an appropriate diet for each patient. The impact of a lower EI on postoperative outcomes and infectious complications was then evaluated.</p><p><strong>Results: </strong>Patients were categorized into three groups according to their EI: Group A (n=57), Group B (n=55), and Group C (n=57). Following hospitalization, the proportion of Group C patients consuming porridge as their staple food increased, while no significant difference was observed between Groups A and B. However, the percentage of patients consuming chopped side dishes increased across all groups. Regarding postoperative outcomes, although there were no differences in EI, nutritional sufficiency ratio (%), and protein intake (g/kg) among the groups, these variables were associated with the dates of diet initiation and IV infusion completion, duration after IV infusion completion, postoperative hospital stay length, and postoperative weight loss rate. Univariate analysis revealed that EI (A/C), EI (B/C), modified Glasgow prognostic score (score 2), prognostic nutritional index (≤40), low psoas muscle index, stage (IV), lymph node metastasis (≥ N1), blood loss, colostomy, and significantly influenced the incidence of postoperative infectious complications (P<0.05). Multivariate analysis revealed that EI (A/C), EI (B/C), modified Glasgow prognostic score (score 2), and blood loss were independent predictors of postoperative infectious complications (P<0.05).</p><p><strong>Conclusions: </strong>Although postoperative nutritional intake was comparable between patients with reduced and adequate occlusal support, those with reduced preoperative occlusal support had worse outcomes. These findings suggest that the EI may be a useful predictor of postoperative infectious complications.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"1013-1024"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649615","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}

{"title":"Clinical and endoscopic characteristics of colorectal sessile serrated lesion with dysplasia: a single-center cross-sectional comparative study.","authors":"Yanping Wu, Yunrong Wang, Bei Zhao, Yifan Li, Weiwei Wang, Wenqi Sun, Longying Xiong, Dan Ge, Jiale Xu, Xiaotan Dou, Xiaoping Zou, Wen Li, Lei Wang, Min Chen","doi":"10.21037/jgo-2024-901","DOIUrl":"10.21037/jgo-2024-901","url":null,"abstract":"<p><strong>Background: </strong>The precancerous lesion of colorectal cancer (CRC), colorectal sessile serrated lesion (SSL), takes an average of 15 years to germinate from no cell dysplasia to CRC, and 2 years for SSL with dysplasia (SSL-D). To date, the impacts of endoscopic and pathological features of SSL and SSL-D on the development of dysplasia remain unclear. In this study, we explored these impacts, striving to provide reference for its classification, detection, and diagnosis.</p><p><strong>Methods: </strong>Retrospectively, a cross-sectional analysis was conducted to compare 414 SSL and 59 SSL-D, which had been diagnosed under colonoscopy in the Affiliated Drum Tower Hospital of Nanjing University.</p><p><strong>Results: </strong>A total of 454 participants were enrolled with a mean age of 58.43±13.94 years and a male-to-female ratio of 0.91:1. There were significant differences between the SSL and SSL-D groups in the gender distribution (P=0.044). The proportion of patients with hypertension (33.33% <i>vs.</i> 17.13%, P=0.004) was higher in the SSL-D group. Significantly higher indexes in lipid metabolism were observed in the SSL-D group. SSL-D had a greater number of lesions ≥10 mm (86.44% <i>vs.</i> 57.00%, P<0.001), 0-IIa morphology (55.93% <i>vs.</i> 41.55%, P=0.049), and kermesinus surface (22.03% <i>vs.</i> 7.49%, P<0.001).</p><p><strong>Conclusions: </strong>Female SSL patients with a history of hypertension are more prone to developing into dysplasia, whereas morphological discriminations between SSL and SSL-D are vague. Lipid metabolism might have certain impact on the germination of SSL to SSL-D. Studies with larger sample sizes are warranted.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"802-810"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649622","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}

{"title":"Path towards personalized care of hepatocellular carcinoma: a nomogram for survival prediction.","authors":"Nicole Tan, Vishal G Shelat","doi":"10.21037/jgo-2025-298","DOIUrl":"10.21037/jgo-2025-298","url":null,"abstract":"","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 3","pages":"1347-1350"},"PeriodicalIF":2.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649648","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}

{"title":"Efficacy and safety of camrelizumab in combination with S-1 plus oxaliplatin sequenced by camrelizumab-based maintenance therapy as a first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: a retrospective cohort study.","authors":"Wan-Ren Peng, Fei Zhang, Wen-Wen Ma, Jie Da, Han-Qing Yu, Lu-Lu Fan, Zhen-Ya Jia, Jing Xu, Zi-Cong Gao, Chang-Chun Shao, Guo-Ping Sun","doi":"10.21037/jgo-2025-189","DOIUrl":"10.21037/jgo-2025-189","url":null,"abstract":"<p><strong>Background: </strong>S-1 plus oxaliplatin (SOX) is a first-line standard-of-care treatment for patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Programmed cell death protein 1 (PD-1) inhibitors plus chemotherapy, including SOX have also shown promising outcomes in such patients. This study was performed to evaluate the efficacy and safety of camrelizumab plus SOX sequenced by camrelizumab-based maintenance therapy as a first-line treatment for advanced G/GEJ adenocarcinoma.</p><p><strong>Methods: </strong>In total, 31 patients with an age of 18 years or older and newly diagnosed with human epidermal growth factor receptor 2 (HER2)-negative advanced G/GEJ adenocarcinoma who underwent camrelizumab in combination with SOX followed by camrelizumab plus S-1 from February 2020 to December 2023 were enrolled in the study. All patients were regularly followed up every 1-2 months. The primary endpoint of the study was progression-free survival (PFS). And the safety profiles were also assessed.</p><p><strong>Results: </strong>As of December 31, 2023, 25 male and 6 female patients were enrolled. The median follow-up time was 14.6 months. The median PFS time of the patients treated with the combination regimen was 7.3 months [95% confidence interval (CI): 3.0-11.6]. In addition, the median overall survival (OS) time was 13.3 months (95% CI: 10.3-16.4), and the median duration of response (DoR) was 5.0 months (95% CI: 2.0-8.1). Moreover, the objective response rate (ORR) and disease control rate (DCR) were 71.0% and 87.1%, respectively. Further, the most commonly observed grade ≥3 adverse events (AEs) were increased gamma-glutamyltransferase (GGT) (9.7%) and a decreased neutrophil count (6.5%). No treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>First-line treatment with camrelizumab in combination with SOX sequenced by camrelizumab-based maintenance therapy demonstrated favorable outcomes for and was well tolerated by patients with advanced G/GEJ adenocarcinoma. Thus, it might serve as a first-line standard-of-care treatment for such patients. However, prospective randomized studies should be carried out to confirm the findings.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"342-353"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093742","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}

{"title":"The highly expressed <i>GOLPH3</i> in colorectal cancer cells activates smoothened to drive glycolysis and promote cancer cell growth and radiotherapy resistance.","authors":"Kunli Zhu, Jing Fan, Hongchao Cai, Changchun Zhou, Zhe Gong, Zhenxiang Li, Jinming Yu","doi":"10.21037/jgo-2025-193","DOIUrl":"10.21037/jgo-2025-193","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a frequently diagnosed cancer across the world and has increased in prevalence over the last decade. This study aimed to assess the biological roles, influences on radiosensitivity, and possible molecular mechanism of Golgi phosphoprotein 3 (<i>GOLPH3</i>) in CRC.</p><p><strong>Methods: </strong>Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) were used to examine GOLPH3 expression. <i>In vivo</i> and <i>in vitro</i> assays were carried out to clarify the function of <i>GOLPH3</i> in CRC. The differentially expressed genes (DEGs) in CRC cells with knockdown of <i>GOLPH3</i> were identified through RNA sequencing (RNA-seq). Based on the DEGs associated with <i>GOLPH3</i> knockdown and the data from The Cancer Genome Atlas (TCGA) database, the pathways that could be regulated by <i>GOLPH3</i> were predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.</p><p><strong>Results: </strong>In CRC, <i>GOLPH3</i> was upregulated, and <i>GOLPH3</i> upregulation was predictive of a poor prognosis. <i>GOLPH3</i> knockdown inhibited CRC cell proliferation, migration, and invasion but promoted apoptosis and reduced radiotherapy resistance. Conversely, in CRC cells with <i>GOLPH3</i> overexpression, malignant biological behavior and radiotherapy resistance were enhanced. <i>In vivo</i>, <i>GOLPH3</i> knockdown impeded tumor growth. Mechanistically, <i>GOLPH3</i> promoted the localization of smoothened (SMO) on the cell membrane, thereby activating AMP-activated protein kinase (AMPK)-mediated glycolysis. Additionally, the final product of glycolysis, lactate, induced H3 lysine 18 lactylation (H3K18), which could be enriched on the promoter of <i>GOLPH3</i> and stimulate the transcription of <i>GOLPH3</i>.</p><p><strong>Conclusions: </strong><i>GOLPH3</i> promoted CRC progression and enhanced radiotherapy resistance via glycolysis mediated by the SMO-AMPK axis.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"415-434"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093979","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}