World Journal Of Gastrointestinal Oncology[JOURNAL]
Sun
200 papers
Downregulation of uncoupling protein 1 by hypermethylation in gastric cancer activates signaling.
Chen YJ, Peng C, Wang LW … +3 more , Chai JX, Wang JD, He QB
World J Gastrointest Oncol · 2025 Sep · PMID 40977672 · Full text
BACKGROUND: Uncoupling protein 1 () plays a pivotal role in modulating energy expenditure and maintaining metabolic homeostasis within brown and beige adipocytes. It has also been implicated in tumorigenesis. AIM: To inv...
BACKGROUND: Uncoupling protein 1 () plays a pivotal role in modulating energy expenditure and maintaining metabolic homeostasis within brown and beige adipocytes. It has also been implicated in tumorigenesis. AIM: To investigate the expression and function of UCP1 in gastric cancer (GC). METHODS: UCP1 protein expression in 211 GC tissues was examined using immunohistochemistry. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the promoter in GC cell lines and tissues. The relationship between UCP1 expression and clinicopathological parameters was analyzed. CCK8, scratch, transwell, and flow cytometry assays were carried out to analyze the proliferation, migration, invasion, and apoptosis of GC cell lines after knockdown or overexpression of UCP1 . A nude mouse tumor xenograft model was used to investigate the function of . RNA sequencing, Kyoto Encyclopedia of Genes and Genomes analysis, and Rap1 pull-down assays were performed to identify the pathway associated with . RESULTS: Loss of UCP1 was significantly associated with gender, poor differentiation, and advanced TNM stage of GC. Hypermethylation of was confirmed in GC cells and tumor tissues by BSP. Overexpression of UCP1 suppressed GC cell proliferation, migration, and invasion, and it promoted apoptosis . UCP1 overexpression also suppressed GC tumor growth . Moreover, overexpression of UCP1 in GC cells resulted in a significant decrease in active Rap1 protein levels, whereas downregulation of UCP1 markedly enhanced Rap1 activity. CONCLUSION: UCP1 downregulation in GC through promoter hypermethylation is related to the progression of GC, indicating that plays a role as a tumor suppressor in GC. It regulates signaling and may be a potential therapeutic target in GC.
Associations among healthcare insurance, tumor-node-metastasis stage and cancer survival: More to be understood.
Li ZY, Wang R, Chen XZ … +1 more , SIGES Research Group
World J Gastrointest Oncol · 2025 Sep · PMID 40977671 · Full text
Cancers remain a major health burden with a high mortality rate in China. Basic medical insurance, is the most important element in the financial support system of healthcare resources in both urban and rural areas, and...
Cancers remain a major health burden with a high mortality rate in China. Basic medical insurance, is the most important element in the financial support system of healthcare resources in both urban and rural areas, and requires further understanding to improve health policy. For instance, a single hospital-based prospective cohort study found that esophageal cancer survival outcomes were associated with different healthcare payment patterns and situations. Comparing the extracted literature-data between urban employee basic medical insurance and urban and rural resident basic medical insurance, the proportions of tumor-node-metastasis (TNM) stage I-II were 27.1% and 34.6%, while those of TNM stage IV were 35.0% and 26.1%, respectively. Additionally, high out-of-pocket rate (> 60%) of hospitalization was associated with a higher proportion of TNM stage I-II (40.3% 26.9%) and a lower proportion of TNM stage IV (22.7% 32.8%). In addition, healthcare payment simultaneously influenced or was influenced by the proportions of early and advanced esophageal cancers. The critical difficulty in improving survival of esophageal cancer in populations should be a low proportion of early disease. A more comprehensive and robust public healthcare insurance system is desired to support cancer prevention and control in particular, in order to increase the proportion of early cancers and consequently improve patient survival. Additionally, commercial medical insurance and social charities hope to be fully introduced and encouraged to achieve these goals as active supplement.
Efficacy of adjuvant chemotherapy in stage II colon cancer patients with twelve or more lymph nodes retrieve.
Huo Y, Zhang YY, Jiao S … +4 more , Bai ZY, Bai WQ, Zhou HT, Guan X
World J Gastrointest Oncol · 2025 Sep · PMID 40977670 · Full text
BACKGROUND: The National Comprehensive Cancer Network guidelines recommend adjuvant chemotherapy (ACT) for patients with stage II colon cancer who have undergone curative surgery when fewer than 12 lymph nodes (LNs) are...
BACKGROUND: The National Comprehensive Cancer Network guidelines recommend adjuvant chemotherapy (ACT) for patients with stage II colon cancer who have undergone curative surgery when fewer than 12 lymph nodes (LNs) are retrieved. This study seeks to further examine the requirement for ACT in individuals who had 12 or more LNs harvested. AIM: To investigate if stage II colon cancer patients with 12 or more LNs retrieved benefit from ACT. METHODS: This retrospective cohort study included individuals diagnosed with stage II colon cancer who underwent surgery between 2008 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) registry and a Chinese multicenter database. All patients had at least 12 LNs retrieved. The key endpoint was overall survival (OS). Cox regression analysis was performed to assess independent OS predictors. Propensity score matching controlled for confounders, and Kaplan-Meier analysis evaluated the impact of ACT on survival. RESULTS: A total of 32742 patients with stage II colon cancer from the SEER cohort and 3153 patients from the Chinese cohort were included. The average number of LNs retrieved was 20.0 (15.0, 26.0) in the SEER cohort and 18.0 (15.0, 22.0) in the Chinese cohort. No-ACT remained an independent risk factor in both cohorts (hazard ratio = 1.589, 95% confidence interval: 1.485-1.700 and hazard ratio = 1.865, 95% confidence interval: 1.465-2.375, respectively). In the SEER cohort, patients in the ACT group consistently demonstrated better 5-year OS rates both before and after propensity score matching (79.4% 66.1% and 79.4% 69.4%, both < 0.0001). Similarly, these findings were further validated in the Chinese cohort (91.2% 82.1% and 90.0% 82.8%, both < 0.0001). ACT improved prognosis even in T3 and grade 1/2 patients. CONCLUSION: This research, based on two large population-based cohorts, demonstrates that stage II colon cancer patients with 12 or more LNs retrieved can still benefit from ACT.
Endoscopic management of pancreatic cystic neoplasms.
Zeng Y, Zhang JW, Yang J
World J Gastrointest Oncol · 2025 Sep · PMID 40977669 · Full text
Pancreatic cystic neoplasms (PCNs) represent a spectrum of heterogeneous lesions with diverse biological behaviors and malignant potential. This category encompasses relatively common subtypes, such as intraductal papill...
Pancreatic cystic neoplasms (PCNs) represent a spectrum of heterogeneous lesions with diverse biological behaviors and malignant potential. This category encompasses relatively common subtypes, such as intraductal papillary mucinous neoplasms, serous cystic neoplasms, and mucinous cystic neoplasms, alongside relatively rarer entities, including cystic degeneration of solid pancreatic tumors. The widespread use of cross-sectional imaging has led to increased incidental detection of PCNs, subsequently driving a surge in PCN-related medical consultations and interventions; thus, standardized management of PCNs demands heightened attention. Continuous advancements in endoscopic technologies, particularly endoscopic ultrasound (EUS) and EUS-guided procedures, now offer diversified diagnostic and therapeutic options, establishing EUS as a pivotal tool for diagnosing, surveillance, and treating PCNs. This review synthesizes current evidence and evolving clinical practices in the endoscopic management of PCNs, emphasizing optimizing preoperative diagnostic accuracy, standardizing endoscopic protocols, implementing subtype-specific risk stratification, promoting multidisciplinary team approaches, and addressing challenges in emerging technologies.
Correlation between sarcopenia diagnosed by C3SMI criteria and prognosis in esophageal cancer patients after radiotherapy.
Wang DE, Qin XF, Yang W
World J Gastrointest Oncol · 2025 Sep · PMID 40977668 · Full text
BACKGROUND: Esophageal cancer is a common malignancy with high mortality. Radiotherapy is an important treatment. Sarcopenia affects patients' physical function and prognosis. However, the relationship between sarcopenia...
BACKGROUND: Esophageal cancer is a common malignancy with high mortality. Radiotherapy is an important treatment. Sarcopenia affects patients' physical function and prognosis. However, the relationship between sarcopenia diagnosed by Chun-Hou Chen method for sarcopenia measurement and index (C3SMI) criteria and esophageal cancer prognosis after radiotherapy is unclear. AIM: To explore the correlation between sarcopenia (SA) diagnosed based on C3SMI criteria and the prognosis of patients with esophageal cancer following radiotherapy. METHODS: A retrospective analysis was conducted on the general clinical data of 131 esophageal cancer patients who received radiotherapy in the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University from March 2021 to July 2024. Based on the presence of SA, the patients were assigned into two groups - the SA group and the non-SA group. Logistic regression analysis was used for investigating the risk factors influencing SA in esophageal cancer patients. Additionally, the patients were followed up, with their prognosis recorded. As per their prognostic outcomes, the patients were allocated into a good prognosis group and a poor prognosis group. The data of the two groups were compared. Using logistic regression analysis, the risk factors that may influence the prognosis of these patients were analyzed. SPSS 26.0 statistical software was introduced for analyzing the study data. Comparisons were made between groups using -tests or tests based on the data type. RESULTS: As revealed through logistic regression analysis, age [odds ratio (OR) = 2.898, = 0.038], body mass index (OR = 5.983, = 0.006), prealbumin (OR = 6.253, = 0.003), and Karnofsky performance status score (OR = 3.854, = 0.010) were independent risk factors impacting SA for esophageal cancer patients ( < 0.05). Logistic regression analysis also found that age (OR = 3.823, = 0.030), differentiation degree (OR = 4.802, = 0.028), American Joint Committee on Cancer clinical staging (OR = 3.732, = 0.013), alpha-fetoprotein level (OR = 3.508, = 0.018), thrombospondin-1 level (OR = 5.749, = 0.006), carcinoembryonic antigen level (OR = 3.873, = 0.030), and SA (OR = 3.593, = 0.017) were independent risk factors that may influence esophageal cancer patients' prognosis ( < 0.05). CONCLUSION: The presence of SA has a significant relation to the poor prognosis of esophageal cancer patients, which highlights the importance of assessing and intervening in SA in clinical management so as to improve patient prognosis.
DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferation ribonucleotide reductase M2.
Qiu ZS, Wang XC, Ma JC … +3 more , Zhu CL, Hu YL, Da MX
World J Gastrointest Oncol · 2025 Sep · PMID 40977667 · Full text
BACKGROUND: Pancreatic cancer (PC) remains one of the most aggressive malignancies, is characterized by rapid progression and high metastatic potential, and is the fourth leading cause of cancer-related mortality worldwi...
BACKGROUND: Pancreatic cancer (PC) remains one of the most aggressive malignancies, is characterized by rapid progression and high metastatic potential, and is the fourth leading cause of cancer-related mortality worldwide. The incidence and mortality rates of PC continue to rise annually. Despite advances in imaging technologies and treatment strategies over the past two decades, the 5-year survival rate for patients with PC remains low, at approximately 13%. Patients with advanced PC still experience dismal outcomes, primarily due to the tumor's aggressiveness and high metastatic capacity. Thus, there is an urgent need to identify reliable molecular biomarkers and therapeutic targets to improve the prognosis of patients with PC. AIM: To investigate the biological functions and mechanisms of DEAD/H-box RNA helicase 10 (DDX10) in PC progression. METHODS: We comprehensively investigated the expression pattern and functional significance of DDX10 in PC using a multi-omics integrative approach. We performed bioinformatics analyses of datasets from The Cancer Genome Atlas and Gene Expression Omnibus, tissue microarray-based immunohistochemistry, and a series of functional assays to assess cellular proliferation, migration, invasion, and apoptosis. Additionally, transcriptomic and proteomic analyses were integrated to delineate the molecular regulatory networks that mediate the aggressive phenotype of PC. RESULTS: DDX10 was found to be significantly overexpressed at both the mRNA and protein levels in PC tissues compared with adjacent non-tumor tissues. Silencing DDX10 led to marked inhibition of PC cell proliferation, migration, and invasion, accompanied by enhanced apoptosis. Integrated RNA sequencing, proteomic profiling, and western blot validation revealed that DDX10 modulates key oncogenes including RRM2, LIG1, CDK6, and ITGA2. Notably, ectopic RRM2 overexpression partially rescued the growth-suppressive effects induced by DDX10 knockdown in PANC-1 cells, and high DDX10 expression is associated with poor overall survival in patients with PC. CONCLUSION: Collectively, our findings indicate that DDX10 promotes PC cell proliferation primarily by upregulating RRM2, thus highlighting its potential as a promising therapeutic target in PC.
Chemotherapy plus bevacizumab chemoimmunotherapy for metastatic colorectal cancer: Real-world analysis.
Gao Z, Zhou ZF, Wang XY … +3 more , Song T, Wu SK, Jin X
World J Gastrointest Oncol · 2025 Sep · PMID 40977666 · Full text
BACKGROUND: Clinical trial evidence points to chemotherapy's potential in augmenting the effects of immunotherapy. AIM: To assess the effectiveness of first-line chemoimmunotherapy (CIT) for microsatellite stable (MSS) m...
BACKGROUND: Clinical trial evidence points to chemotherapy's potential in augmenting the effects of immunotherapy. AIM: To assess the effectiveness of first-line chemoimmunotherapy (CIT) for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) verses standard-of-care (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab). METHODS: This was a multicenter retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received first-line treatment were eligible. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate progression-free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). PFS was set as the primary endpoint. Propensity score (PS) was calculated to balance the baseline characteristics of the two cohorts. With PS, we performed three statistical methods, namely inverse probability weighting, PS matching, and additional adjustment for PS with multivariate cox regression. RESULTS: Between July 2019 and November 2024, 148 eligible patients were enrolled, with 40 and 108 patients assigned to the CIT and SOC cohorts, respectively. At a global median follow-up of 21.4 months, the crude median PFS was 13.5 months (95%CI: 9.77-21.6) in the CIT cohort 9.1 months (95%CI: 7.8-10.6) in the SOC cohort, yielding a nonsignificant hazard ratio (HR) of 0.5645 (95%CI: 0.3637-0.8763, = 0.01; SOC as reference). Multivariate Cox regression analysis, adjusted for sex, age > 60 years, Eastern Cooperative Oncology Group performance status, rat sarcoma mutation, primary tumor location (left right) and number of metastatic organs (liver/lung), demonstrated an adjusted HR of 0.55 (95%CI: 0.35-0.87, = 0.011). PS-based analyses using PS matching (post-matching = 40 40), PS-adjusted multivariate Cox regression, and inverse probability weighting revealed consistent significant trends favoring CIT, with HRs for CIT of 0.5641 (95%CI: 0.3303-0.9635, = 0.0361), 0.60 (95%CI: 0.38-0.96, = 0.034), and 0.57 (95%CI: 0.337-0.973, = 0.039), respectively. CONCLUSION: Efficacy of CIT in MSS mCRC could surpass that of standard first-line chemotherapy. Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from CIT.
Prognostic factors and efficacy of postoperative chemotherapy in patients with gastric cancer with positive peritoneal cytology after gastrectomy.
Sugiyama Y, Tanabe K, Yanagawa S … +12 more , Tazawa H, Toyota K, Kano M, Misumi T, Shishida M, Okano K, Hotta R, Ota H, Imaoka Y, Fukuda T, Takahashi S, Ohdan H
World J Gastrointest Oncol · 2025 Sep · PMID 40977665 · Full text
BACKGROUND: Peritoneal lavage cytology-positive (CY1) gastric cancer (stage IV) has a poor prognosis, though some cases fare better. Therefore, identifying prognostic factors and an optimal treatment strategy is crucial....
BACKGROUND: Peritoneal lavage cytology-positive (CY1) gastric cancer (stage IV) has a poor prognosis, though some cases fare better. Therefore, identifying prognostic factors and an optimal treatment strategy is crucial. AIM: To investigate prognostic factors in patients with gastric cancer who underwent gastrectomy with CY1, and to evaluate the optimal postoperative chemotherapy regimen. METHODS: This multicenter retrospective cohort study analyzed prognostic factors and postoperative chemotherapy in patients with CY1 gastric cancer who underwent gastrectomy, excluding those with macroscopic peritoneal dissemination. Data from 13 institutions (2015-2019) were reviewed. RESULTS: Overall, 82 patients met the inclusion criteria. The median overall survival was 22.8 months, and diffuse-type histology and the absence of postoperative chemotherapy were identified as independent poor prognostic factors. The 5-year survival rate was 82.4% for those receiving fluoropyrimidine plus docetaxel/oxaliplatin 21.8% for those with S-1 monotherapy or a cisplatin-based regimen. Median overall survival was not reached in the fluoropyrimidine + docetaxel/oxaliplatin group but was 22.9 months in the S-1/cisplatin group. Chemotherapy regimen was an independent prognostic factor (hazard ratio = 5.47, = 0.004). The fluoropyrimidine plus docetaxel/oxaliplatin group had an average relative dose intensity of 82.1%, with significantly more patients achieving a relative dose intensity ≥ 80% than in the S-1 monotherapy or cisplatin-based group ( = 0.001). CONCLUSION: Diffuse-type histology and the absence of postoperative chemotherapy influence the prognosis of patients with CY1 gastric cancer. Combination therapy with oxaliplatin or docetaxel may enhance the treatment intensity and improve survival outcomes after gastrectomy.
Missing link: Viral RNA signatures in circulating exosomes as early diagnostic biomarkers for gastrointestinal cancers.
Darweesh M, Mohammadi S
World J Gastrointest Oncol · 2025 Sep · PMID 40977664 · Full text
This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal (GI) cancers. Current diagnostic methods...
This editorial highlights the critical role of viral RNA signatures encapsulated within circulating exosomes as a potential missing link in the early diagnosis of gastrointestinal (GI) cancers. Current diagnostic methods for virus-associated GI malignancies often fall short in detecting infections at subclinical or pre-cancerous stages. We propose that viral RNA-loaded exosomes, by offering stable, specific, and non-invasive biomarkers, can bridge this gap and revolutionize early detection compared to conventional approaches. As highlighted by Zhang in their recent review, viral infections, such as hepatitis B and C viruses, Epstein-Barr virus, and human papillomavirus, are well-established contributors to the pathogenesis of various GI malignancies. However, current diagnostic methods often underperform in detecting these infections at subclinical or pre-cancerous stages. We highlight the shared points between virology, exosome biology, and oncology, reinforcing the importance of viral RNA-loaded exosomes as a "missing link" in the early detection of virus-associated GI cancers. We also discuss current challenges, translational opportunities, and the requirements for clinical validation of these promising biomarkers.
Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma.
Zhan TA, Xia F, Huang HW … +3 more , Zhan JC, Liu XK, Cheng Q
World J Gastrointest Oncol · 2025 Sep · PMID 40977663 · Full text
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with limited therapeutic progress for advanced stages. The aberrant fibroblast growth factor 19 (FGF19)-fibroblast growth facto...
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with limited therapeutic progress for advanced stages. The aberrant fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) axis promotes oncogenesis and is linked to targeted-immunotherapy of HCC. Multi-kinase inhibitors (MKIs) enhance anti-tumor effects by targeting this axis and FGF19 overexpression upregulates programmed cell death ligand 1 in tumor microenvironment. Clinical studies have demonstrated the efficacy of selective FGFR4 inhibitors in HCC treatment, with enhanced anti-tumor effects when combined with MKIs or immune checkpoint inhibitors. Phase I clinical trials of Irpagratinib (ABSK-011) demonstrated an objective response rate of 43.5%, which increased to 55.6% combined with atezolizumab. FGF19 also serves as a biomarker for HCC. This review systematically summarizes the literature retrieved from PubMed and other databases using search terms "HCC", "fibroblast growth factor 19", "fibroblast growth factor receptor 4", "FGFR4 inhibitor", "targeted therapy", "multi-kinase inhibitor", "immunotherapy", "immune checkpoint inhibitor", and "biomarker". It also firstly synthesizes combination strategies and underlying mechanisms between FGFR4 inhibitors and targeted-immunotherapy, addressing critical gaps in existing reviews. Additionally, we discuss the potential of FGF19 as a predictive biomarker, integrating mechanistic and clinical evidence to advance precision HCC therapeutics.
Ginsenoside F4 inhibits colorectal cancer progression by boosting dendritic cell maturation and remodeling the tumor microenvironment.
Xie W, Li XJ, Zhong YS … +5 more , Fang J, Qi H, Yang M, Ying HZ, Yu CH
World J Gastrointest Oncol · 2025 Sep · PMID 40977662 · Full text
BACKGROUND: Immunotherapy that employs dendritic cells (DCs) to activate the patient's immune system has emerged as a promising therapeutic strategy to combat cancer; however, effective targeting agents are still limited...
BACKGROUND: Immunotherapy that employs dendritic cells (DCs) to activate the patient's immune system has emerged as a promising therapeutic strategy to combat cancer; however, effective targeting agents are still limited. Ginsenoside F4, as a rare ginsenoside found in , exhibits stronger antitumor and immunomodulatory activities than primary ginsenosides. However, its therapeutic effects on various diseases remain limited. AIM: To investigate the antitumor effect of Ginsenoside F4 and mechanism on the maturation of DCs in colorectal cancer (CRC). METHODS: The changes in mature DC markers and cytokines generated after DCs were exposed to F4 were assessed using flow cytometry and enzyme-linked immunosorbent assay, respectively. The viability of CRC CT26 cells co-cultured with T lymphocytes was monitored by cell counting kit-8 assay. Furthermore, the histopathological characteristics and immune cell infiltration in tumor tissues of CT26-bearing mice were analyzed by hematoxylin-eosin and immunofluorescent staining. The expressions of apoptosis-relative proteins were detected by western blot assay. RESULTS: Treatment with F4 promoted the maturation of DCs, elevated the expressions of cluster of differentiation (CD) 83 and CD86, increased the secretion of interleukin (IL)-2, IL-10, and IL-12 p70, and upregulated the expressions of phosphorylated phosphoinositide 3-kinase, phosphorylated protein kinase B, and nuclear factor kappa-B (NF-κB) phosphorylated p65 in DCs, which enhanced antigen-specific CD8+ T-cell responses. However, these benefits could be reversed by the sphingosine-1-phosphate 1 (S1PR1) inhibitor fingolimod hydrochloride. Furthermore, oral administration with F4 inhibited tumor growth and increased DC and CD8+ T-cell infiltration in the tumor tissues of CT26-bearing mice. CONCLUSION: The results demonstrated that F4 inhibited the growth of CRC by maturing DCs through activating S1PR1-mediated phosphoinositide 3-kinase/protein kinase B and NF-κB pathways, which triggered the antitumor effects of CD8+ T cells. Therefore, F4 could serve as an antitumor immunomodulator for CRC treatment.
Rapamycin suppresses small bowel adenocarcinoma HUTU 80 cells proliferation by inhibiting hypoxia-inducible factor-1α mediated metabolic reprogramming.
Pu BP, Wang PH, Guo KK … +6 more , Liu C, Chen SR, Li XM, Chen SM, Zeng XZ, Gao C
World J Gastrointest Oncol · 2025 Sep · PMID 40977661 · Full text
BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignant tumor of gastrointestinal tract. Currently, there is no standard treatment approach for late-stage SBA, which lead to poor outcome and prognosis. Rapamycin...
BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignant tumor of gastrointestinal tract. Currently, there is no standard treatment approach for late-stage SBA, which lead to poor outcome and prognosis. Rapamycin is an immunosuppressive agent that has been reported to inhibit the proliferation of tumor cells. However, whether rapamycin inhibit the growth of SBA remains to be investigated. AIM: To observe the inhibitory effect of rapamycin on small intestinal adenocarcinoma cells. METHODS: Methylthiazolyldiphenyl-tetrazolium bromide assay, colony formation assay, cell cycle analysis, and glycolysis assay were used to observe the phenotypic changes of rapamycin-treated HUTU 80 cells. RNA sequencing and untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics were also used to find the potential targets of action of rapamycin in inhibiting HUTU 80 cells proliferation, and validate potential targets by quantitative polymerase chain reaction and western blotting. The construction of a subcutaneous HUTU 80 xenograft in BALB/c nude mice was used to explore the tumor suppression effect of rapamycin. RESULTS: Rapamycin inhibited HUTU 80 cell proliferation and . Rapamycin inhibited the migration, invasion, and glycolysis of HUTU 80 cells, and induced cell cycle arrest. RNA sequencing and untargeted UHPLC-MS/MS metabolomic analysis indicated that the mechanism of rapamycin action was linked to the hypoxia-inducible factor (HIF)-1α signaling pathway and the related gluconeogenesis/glycolysis pathways. Subsequent experiments found that rapamycin downregulated the messenger RNA expression of HIF-1α and its downstream target genes, , and . Additionally, rapamycin inhibited expression of phosphorylated mammalian target of rapamycin (mTOR), phosphorylated-70 kDa ribosomal protein S6 kinase (p70S6k), phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and HIF-1α proteins and . CONCLUSION: Downregulation of mTOR/p70S6k/4E-BP1/HIF-1α signaling pathway activation, leading to decreased glycolysis and cell cycle arrest, may be the pivotal mechanism by which rapamycin inhibits SBA.
Status quo of hypercoagulation as a prognostic indicator following neoadjuvant immunochemotherapy in locally advanced gastric cancer.
Christodoulidis G, Bartzi D, Tsagkidou K … +2 more , Koumarelas KE, Zacharoulis D
World J Gastrointest Oncol · 2025 Sep · PMID 40977660 · Full text
Gastric cancer remains a major cause of cancer-related mortality worldwide, with immunotherapy emerging as a promising treatment strategy. Neoadjuvant immune checkpoint therapy has shown potential in enhancing antitumor...
Gastric cancer remains a major cause of cancer-related mortality worldwide, with immunotherapy emerging as a promising treatment strategy. Neoadjuvant immune checkpoint therapy has shown potential in enhancing antitumor responses and improving surgical outcomes. However, its effects on systemic coagulation and thrombotic risk remain poorly understood. This study aims to investigate the relationship between neoadjuvant immune checkpoint therapy and coagulation dynamics in patients with gastric cancer, exploring potential mechanisms that may contribute to a hypercoagulable state. By assessing coagulation markers, thrombotic events, and inflammatory responses, this research seeks to provide insights into the interplay between immune modulation and hemostatic alterations. A better understanding of these interactions may help optimize patient management and guide thromboprophylaxis strategies in this clinical setting.
Irreversible electroporation combined with checkpoint blockade stimulates antitumor immune response in a hepatocellular carcinoma mouse model.
Xing YL, Li HM, Pang XM … +6 more , Zhang Y, Yang T, Li YH, Liu DC, Ma YY, Niu LZ
World J Gastrointest Oncol · 2025 Sep · PMID 40977659 · Full text
BACKGROUND: Irreversible electroporation (IRE) represents an innovative localized technique for tumor ablation, possessing the capacity to activate the immune response of the host. However, this method alone is inadequat...
BACKGROUND: Irreversible electroporation (IRE) represents an innovative localized technique for tumor ablation, possessing the capacity to activate the immune response of the host. However, this method alone is inadequate to halt cancer progression, necessitating the integration of additional strategies to achieve effective immunotherapy. AIM: To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1 (PD-1) therapy within a murine model of hepatocellular carcinoma. METHODS: C57BL-6 mice with tumor growth were divided into four separate cohorts: Control group; IRE group; Anti-PD-1 group; And IRE + anti-PD-1 group. The infiltration levels of T, B, and natural killer cells within the tumors, as well as the plasma concentrations of T helper type 1 cytokines (interleukin-2, interferon-γ, and tumor necrosis factor-β), were evaluated. Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation (CD) 8 (a marker indicative of CD8 T cells) in the tumor specimens of the mice at various temporal intervals. Tumor growth trajectories were charted. RESULTS: The results indicated that the IRE + anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration, particularly CD4 and CD8 T cells, when compared to the control cohort. Additionally, this group displayed increased infiltration of natural killer and B cells, augmented cytokine levels, and elevated CD8 messenger RNA expression. A marked decrease in tumor volume was noted in the IRE + anti-PD-1 group, indicating enhanced therapeutic efficacy. CONCLUSION: The combined application of IRE and checkpoint blockade elicits an antitumor immune response, leading to a more substantial reduction in tumor volume and improved therapeutic outcomes, thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.
Local excision in rectal cancer: When and for whom?
Demirli Atici S, Canda AE, Terzi MC
World J Gastrointest Oncol · 2025 Sep · PMID 40977658 · Full text
Local excision (LE) is an effective treatment option for rectal cancer that shows significant regression following neoadjuvant chemoradiotherapy. Compared to traditional total mesorectal excision (TME), LE can achieve co...
Local excision (LE) is an effective treatment option for rectal cancer that shows significant regression following neoadjuvant chemoradiotherapy. Compared to traditional total mesorectal excision (TME), LE can achieve comparable oncological outcomes while preserving function and improving quality of life (QoL). The indications for LE have been gradually expanded, but there are uncertainties regarding postoperative oncological results. Long-term follow-up prospective randomized controlled trials comparing TME and LE in terms of both oncological outcomes and QoL could help reduce uncertainties between these two approaches and contribute to the development of evidence-based guidelines for rectal cancer treatment.
Comparative impact of antiviral therapies on postoperative recurrence risk in patients with hepatitis B virus-related hepatocellular carcinoma.
Liu HM, Zhang X, Huang HY … +2 more , Sun JM, Tong QD
World J Gastrointest Oncol · 2025 Sep · PMID 40977657 · Full text
BACKGROUND: Entecavir (ETV) and tenofovir fumarate (TDF) are recommended first-line agents for the treatment of chronic hepatitis B virus (HBV) infection. However, the effect of these 2 antiviral agents on the risk for r...
BACKGROUND: Entecavir (ETV) and tenofovir fumarate (TDF) are recommended first-line agents for the treatment of chronic hepatitis B virus (HBV) infection. However, the effect of these 2 antiviral agents on the risk for recurrence of HBV-associated hepatocellular carcinoma (HCC) after radical hepatectomy remains controversial. AIM: To compare the effect of TDF ETV on the risk for HCC recurrence after radical surgery for HBV-related HCC. METHODS: Data from consecutive patients, who received TDF or ETV after radical hepatectomy for HBV-related HCC and admitted to the Second Hospital of Longyan between December 2018 and December 2023, were retrospectively analyzed. Based on treatment method and propensity score matching (PSM), data from 100 patients were included, with 50 in each of the TDF and ETV groups, respectively. The baseline characteristics of the 2 groups were analyzed, and the risk for HCC recurrence was compared between the groups. RESULTS: The median follow-up for 100 patients [median age, 61 years; 84 male (84%)] who underwent radical resection for HBV-related HCC - Barcelona Clinic Liver Cancer stage 0 [ = 16 (16%)], stage A [ = 61 (61%)] - was 29 months (range, 12-60 months); the median tumor size was 3.0 cm (range, 2.1-4.3 cm). Sixty-eight (68%) patients exhibited HBV-DNA levels > 1000 IU/mL. Twenty-two (22%) patients tested positive for hepatitis B e antigen, in whom the HCC recurrence rate was 59.1% (13/22). After PSM, HCC recurrence rates in the ETV and TDF groups after hepatectomy were 66% ( 33) and 42% ( 21), respectively ( = 0.016), and cumulative recurrence rates at 1, 3, and 5 years were 26%, 58%, and 66%, and 18%, 38%, and 42%, respectively ( = 0.045). CONCLUSION: TDF treatment is associated with a lower risk for HCC-related outcomes than that for ETV in patients with HBV-associated HCC after curative therapy.
Study of serum tumor markers in the early diagnosis of pancreatic cancer.
Deng QX, Tang XL, Yuan GJ … +3 more , Jian Q, Chen XH, Wu LJ
World J Gastrointest Oncol · 2025 Sep · PMID 40977656 · Full text
BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, primarily due to its late diagnosis. Current gold-standard diagnostic methods, such as tissue histopathological examination, are in...
BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, primarily due to its late diagnosis. Current gold-standard diagnostic methods, such as tissue histopathological examination, are invasive and carry risks of complications (, bleeding, infection, pancreatic fistula), limiting their routine use. Serum tumor markers [carbohydrate antigen 19-9 (CA-19-9), carcinoembryonic antigen (CEA)] have been widely studied for non-invasive screening, but their single use lacks sufficient sensitivity and specificity for early detection. Emerging research suggests that inflammatory and stromal-related molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1) (involved in tumor cell adhesion and metastasis) and chitinase-3-like protein 1 (CHI3 L1) (a marker of tissue remodeling and inflammation), may complement traditional markers in improving diagnostic accuracy. However, their combined utility in pancreatic cancer diagnosis, particularly for differentiating early-stage tumors, remains unclear. AIM: To explore the application value of serum tumor markers (CA-19-9, CEA) and serum sICAM-1 and CHI3 L1 in the early diagnosis of pancreatic cancer. METHODS: From October 2021 to October 2024, 51 patients with pancreatic cancer were selected for the pancreatic cancer group, and 51 healthy examinees were selected for the healthy group during the same period. The value of serum tumor markers in combination with serum sICAM-1 and CHI3 L1 for the early diagnosis of pancreatic cancer was assessed. RESULTS: Comparison of age, gender, body mass index, and drinking and smoking histories between the two groups was not statistically significant ( > 0.05); serum tumor marker (CA-19-9, CEA), serum sICAM-1 and CHI3 L1 levels were higher in the pancreatic cancer group ( < 0.05); pancreatic cancer patients of stage II had higher serum tumor marker (CA-19-9, CEA), serum sICAM-1, and CHI3 L1 values ( < 0.05); serum tumor markers, serum sICAM-1, and CHI3 L1 were positively correlated with pancreatic cancer ( < 0.05) and showed a positive correlation with stage I and stage II. Pancreatic cancer showed a positive correlation ( < 0.05); multifactor logistic regression analysis showed that serum tumor markers (CA-19-9, CEA), serum sICAM-1 and CHI3 L1 were independent risk factors for pancreatic cancer ( < 0.05); serum tumor markers (CA-19-9, CEA), serum sICAM-1, serum tumor marker (CA-19-9, CEA) and serum sICAM-1 and CHI3 L1 had area under the curves (AUCs) of 0.750, 0.724, 0.585, and 0.562 for pancreatic cancer diagnosis, respectively; AUCs for stage I diagnosis were 0.766, 0.752, 0.622, and 0.572 and for stage II diagnosis were 0.783, 0.758, 0.626, and 0.671, respectively, and the AUCs for the combined diagnosis of pancreatic cancer, stage I pancreatic cancer, and stage II pancreatic cancer were 0.782, 0.824, and 0.862, respectively ( < 0.05). CONCLUSION: The combined detection of serum tumor markers with serum sICAM-1 and serum CHI3 L1 can significantly improve the accuracy and sensitivity of the diagnosis of pancreatic cancer and its different stages.
Construction of a risk prediction model for early postoperative recurrence in stage II/III colorectal cancer.
Xiong FC, Luo MP, Ruan SM
World J Gastrointest Oncol · 2025 Sep · PMID 40977655 · Full text
BACKGROUND: Colorectal cancer (CRC) recurrence within a year post-surgery poses significant challenges for stage II/III patients. Few models currently predict this early recurrence with multi-dimensional considerations f...
BACKGROUND: Colorectal cancer (CRC) recurrence within a year post-surgery poses significant challenges for stage II/III patients. Few models currently predict this early recurrence with multi-dimensional considerations for risk stratification. AIM: To develop a model for predicting the risk of recurrence within one year after surgery in patients with stage II/III CRC. METHODS: We conducted a retrospective cohort study at Zhejiang Provincial Hospital of Chinese Medicine, including 349 stage II/III CRC patients. Clinical data were collected, and the dataset was randomly divided into training ( = 244) and testing ( = 105) sets. Univariate and multivariate logistic regression analyses identified risk factors for postoperative recurrence. Then a nomogram model was constructed and evaluated receiver operating characteristic curves, calibration curves and decision curve analysis. RESULTS: During the one-year follow-up, 10.9% (38/349) of patients experienced recurrence. Univariate analysis identified tumor size, lymph node metastasis (N2 stage), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, fatigue, and appetite loss as significant correlates of recurrence. Multivariate logistic regression confirmed N2 stage, appetite loss, tumor size, and neutrophil-to-lymphocyte ratio as independent risk factors. The nomogram model showed excellent performance. The area under the receiver operating characteristic was 0.98 (95% confidence interval: 0.97-1.00) in training set and 0.91 (95% confidence interval: 0.84-0.97) in testing set. The decision curve analysis curves showed strong concordance between predicted and observed recurrence probabilities. CONCLUSION: The model effectively predicts early postoperative recurrence in stage II/III CRC, integrating clinical, inflammatory, and symptomatic factors.
Correlation between KAT6A and PD-L1 expression and role of KAT6A in colorectal cancer.
Zhou ZD, Zhao JP, Zheng SC … +1 more , Wang TT
World J Gastrointest Oncol · 2025 Sep · PMID 40977654 · Full text
BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective cancer treatments; however, a significant proportion of colorectal cancer (CRC) patients exhibit limited responses to ICI therapy. KAT6A has been strongly ass...
BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective cancer treatments; however, a significant proportion of colorectal cancer (CRC) patients exhibit limited responses to ICI therapy. KAT6A has been strongly associated with cancer initiation and progression. AIM: To examine the role of KAT6A in CRC progression and immune evasion. METHODS: The functional role of KAT6A was evaluated through genetic knockdown, pharmacological inhibition (WM-3835), and CRISPR/dCas9-mediated epigenetic editing in CRC cells. T cell-mediated apoptosis was assessed using co-culture models, and H3K23pr was measured chromatin immunoprecipitation assays. PD-L1 expression at mRNA and protein levels was analyzed under KAT6A knockdown conditions. RESULTS: KAT6A suppression reduced CRC cell proliferation, invasion, and migration. Pharmacological or epigenetic disruption of KAT6A phenocopied these effects, with dose-dependent reductions in H3K23pr (28.4% residual at 10 μM) and PD-L1 expression. KAT6A knockdown enhanced T cell-mediated apoptosis, evidenced by increased expression of granzyme B and perforin. Mechanistically, KAT6A loss decreased H3K23pr and reduced RNA polymerase II occupancy on the PD-L1 promoter, leading to suppressed PD-L1 transcription. CRISPR/dCas9-mediated H3K23pr editing at the PD-L1 promoter directly modulated immune evasion, confirming its causal role. Overexpression of PD-L1 mitigated the inhibitory effects of KAT6A knockdown on CRC progression and immune evasion. CONCLUSION: KAT6A drives CRC progression and immune evasion by promoting histone H3 propionylation to epigenetically activate PD-L1 expression. Targeting KAT6A or its downstream H3K23pr-PD-L1 axis represents a promising therapeutic strategy to overcome ICI resistance in CRC.
Correlation between perineural invasion and clinicopathological characteristics in pancreatic cancer.
Lu XL, Ge C, Wang RC … +1 more , Zang H
World J Gastrointest Oncol · 2025 Sep · PMID 40977653 · Full text
BACKGROUND: Perineural invasion (PNI) is common in pancreatic cancer (PC) and is associated with poor prognosis. AIM: To investigate the correlation between PNI and clinical pathological features in PC. METHODS: Patients...
BACKGROUND: Perineural invasion (PNI) is common in pancreatic cancer (PC) and is associated with poor prognosis. AIM: To investigate the correlation between PNI and clinical pathological features in PC. METHODS: Patients were retrospectively divided into non-neural invasion and neural invasion groups based on PNI. Differences in tumor location, size, carbohydrate antigen 19-9 (CA19-9) level, overall survival, abdominal pain, pathological type, differentiation, and lymph node invasion were compared. Correlation and logistic regression analyses were performed, and a predictive model was constructed. RESULTS: The neural invasion group had a higher proportion of tumors in the head, larger size, higher CA19-9 levels, lower survival rates, more abdominal pain, and more lymph node invasion. Pancreatic ductal adenocarcinoma and higher differentiation were more common in the neural invasion group. Tumor location, survival, and differentiation were negatively correlated, while size, CA19-9 level, abdominal pain, and lymph node invasion were positively correlated with neural invasion. Tumor location, size, CA19-9 level, abdominal pain, differentiation, and lymph node invasion were independent risk factors. The predictive model showed good consistency with actual occurrence rates. CONCLUSION: Tumor location, size, CA19-9 level, abdominal pain, differentiation, and lymph node invasion are important factors in neural invasion and tumor progression in PC.
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