Journal of gastrointestinal oncology最新文献

{"title":"Downregulation of CPT2 promotes proliferation and migration through the TNFα/NF-κB pathway in cholangiocarcinoma.","authors":"Jun Mao, Genfa Yi, Henghai Yu, Qiaoli Qu, Ying Hu","doi":"10.21037/jgo-24-685","DOIUrl":"10.21037/jgo-24-685","url":null,"abstract":"<p><strong>Background: </strong>Carnitine palmitoyltransferase II (CPT2) is an important regulatory enzyme involved in fatty acid oxidation; it is associated with the prognosis and progression of colorectal and ovarian cancers, but its expression and role in cholangiocarcinoma (CCA) have been less explored. This study aims to explore the role and molecular mechanism of CPT2 in CCA and to determine the potential relationship between CPT2 expression and the prognosis of CCA patients.</p><p><strong>Methods: </strong>Bioinformatics analyses were used to assess CPT2 expression in CCA and other cancers. Independent prognostic factors of CCA were identified for univariate and multivariate Cox regression analyses. Nomograms were employed to predict CCA 1-, 3-, and 5-year survival. Kaplan-Meier curves explored the correlation between CPT2 expression and CCA survival. We used time-dependent receiver operating characteristics (ROCs) to evaluate the predictive efficiency of CPT2. Furthermore, potential mechanisms of CPT2 were analyzed by Gene Set Enrichment Analysis (GSEA) in CCA. CPT2 expression in peripheral blood, tissues, and cell lines of CCA was verified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of CPT2 on CCA cells was gauged using Cell Counting Kit-8 (CCK-8), cell cycle, apoptosis, and transwell assays. Finally, the regulation of the TNFα/NF-κB pathway by CPT2 was verified by Western blotting.</p><p><strong>Results: </strong>CPT2 expression was down-regulated in many cancers, including CCA. COX regression analyses showed that CPT2 expression and the clinical stage could be independent prognostic factors in CCA. Nomograms indicated that the lower probability of CCA survival was associated with the lower expression of CPT2 and the higher clinical stage. The Kaplan-Meier curve showed that the low expression of CPT2 was related to a poor prognosis in CCA. The time-dependent ROC curve demonstrated the predictive ability of CPT2 [1-, 3-, 5-year are under the curve (AUC) =0.933, 0.61, 0.612]. Functionally, CPT2 overexpression inhibited CCA cell proliferation, down-regulated CDK4/6 expression to arrest CCA cells at G1, induced apoptosis by up-regulating BAX expression, cleaved-caspase-3 expression, and down-regulating Bcl2 expression, and reduced migration and invasion via suppression of epithelial-mesenchymal transition (EMT). Knocking down CPT2 showed the opposite results. Mechanistically, overexpression of CPT2 could decrease TNFα and phosphorylated p65 (p-p65; Ser536) expression and inhibit NF-κB pathway activation. CPT2 knockdown yielded opposite results.</p><p><strong>Conclusions: </strong>CPT2 is a potential prognostic marker of CCA, a tumor suppressor gene to inhibit the malignant progression of CCA, and therefore a potential therapeutic target.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"679-698"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093717","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":"Humor me with calcium: a case report of humoral hypercalcemia of malignancy secondary to cholangiocarcinoma.","authors":"Kaiser Kabir, David I LeRoy, Bhavana Liyanaarachchi, Zainab Shams, Ved Singla","doi":"10.21037/jgo-2024-986","DOIUrl":"10.21037/jgo-2024-986","url":null,"abstract":"<p><strong>Background: </strong>Humoral hypercalcemia of malignancy (HHM) is a rare presentation of cholangiocarcinoma, with few reports in prior literature. HHM is due to the production of parathyroid hormone related peptide (PTHrP) from malignant tissues leading to hypercalcemia, often hard to control. Currently, HHM due to cholangiocarcinoma has been associated with poor prognosis and therapies utilized to manage HHM have not been shown to increase survival. Furthermore, biomarkers such as cytokeratin-7 (CK7) have been shown to correlate with worse prognosis in cholangiocarcinoma. While surgical treatment can be curative for cholangiocarcinoma, current nonsurgical treatment options for HHM due to cholangiocarcinoma have not been associated with improved prognosis.</p><p><strong>Case description: </strong>We present a rare case of HHM secondary to cholangiocarcinoma. This case presents a rare case of HHM due to cholangiocarcinoma with an atypical presentation in a 55-year-old female. This patient presented with abdominal swelling and severe hypercalcemia prompting evaluation for a possible gastrointestinal source and was found to have HHM due to cholangiocarcinoma. She was treated for her hypercalcemia medically, however due to the extent of her disease she was unable to undergo surgery. Chemotherapy was not considered during her initial presentation as she originally had a malignancy of unknown primary. Ultimately, shortly after her initial presentation, the patient passed at another hospitalization 36 days after her initial presentation.</p><p><strong>Conclusions: </strong>HHM rarely presents in cholangiocarcinoma, and of the reported cases, it is often associated with poor prognosis. Given the complexity of these cases, a multi-disciplinary approach is necessary for optimal management of these patients. The ability to risk-stratify patients with unique presentations such as this is crucial for accurate diagnosis and potential treatment. HHM in cholangiocarcinoma is poorly studied due to its rarity; however, given the prognosis of this syndrome, further research is essential for earlier detection and better treatments.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"719-725"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093730","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":"Systemic chemotherapy in patients with unresectable pseudomyxoma peritonei from low-grade appendiceal mucinous neoplasms: a case series.","authors":"Mason Vierra, Ryan B Morgan, Arsha Ostowari, Kiran K Turaga, Ardaman Shergill, Oliver S Eng","doi":"10.21037/jgo-24-440","DOIUrl":"10.21037/jgo-24-440","url":null,"abstract":"<p><strong>Background: </strong>Patients with unresectbale low-grade appendiceal mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP) have very few viable treatment options. While aggressive appendiceal pathologies benefit from systemic chemotherapy, it is not clear whether LAMNs do. This is partly due to the rarity of the disease and the heterogeneity in its classification and description in the literature. The purpose of this case series is to describe our institutional experience treating 5 patients with unresectable PMP secondary to LAMN with systemic chemotherapy.</p><p><strong>Case description: </strong>A retrospective analysis was performed of all patients presenting to the University of Chicago Medical Center with PMP from LAMN between 2016-2020. Of 72 patients who underwent treatment for PMP from LAMN during this period, 5 patients with unresectable disease who had received systemic chemotherapy were included in analysis. Median age was 54 years and median peak peritoneal cancer index was 39. All patients received either folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) as first line therapy, undergoing a median of 7 cycles of chemotherapy; 3 patients received anti-vascular endothelial growth factor (VEGF) therapy. Median progression-free survival (PFS) was 10.3 (range, 3.2-21.4) months with a median follow-up of 21.5 months. Although four patients with elevated carcinoembryonic antigen (CEA) at baseline showed a trend toward a CEA response after receiving chemotherapy, none demonstrated an imaging response to chemotherapy and none became resectable.</p><p><strong>Conclusions: </strong>Although our case series is small, it is the first to specifically describe the outcomes of patients with unresectable metastatic peritoneal disease from LAMNs treated with oxaliplatin-based systemic chemotherapy. PFS while on systemic chemotherapy for unresectable LAMN was consistent with previously described outcomes in heterogenous populations. Larger, prospective studies will be needed to define the exact benefit of chemotherapy in unresectable LAMNs.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"757-765"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093978","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":"Construction of a survival prediction model for patients with hepatocellular carcinoma (HCC) based on real clinical data: a single-center retrospective study.","authors":"Ya-Hui Liu, Yun-Wei Yan, Shu-Fan Wei, Wen-Juan Wang, Hong-Ji Zeng, Rui Wang, Qing-Feng Tian","doi":"10.21037/jgo-24-806","DOIUrl":"10.21037/jgo-24-806","url":null,"abstract":"<p><strong>Background: </strong>Given the rising incidence of hepatocellular carcinoma (HCC) globally, especially in China, information about independent risk factors for survival and disease prognosis of the illness is scarce. In the field of HCC research, there is an urgent need for a scientific basis to enhance the accuracy of clinical diagnosis, optimize the course of therapy, and accurately predict the prognosis. Against this backdrop, the objective of this work was to develop a scientific, efficient, and methodical nomogram to forecast the survival prognosis of HCC.</p><p><strong>Methods: </strong>A real-world study collected clinical data from January 1, 2011, to December 31, 2019, for individuals with HCC. Overall survival (OS) was determined using Kaplan-Meier analysis. Independent risk variables were identified using Cox proportional hazards regression. A nomogram predicting 1-, 3-, and 5-year OS was created. The reliability of the predictions of the model was assessed using receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Data from 1,128 HCC cases showed 1-, 3-, and 5-year OS rates were 86.3%, 65.3%, and 43.1%, respectively. Univariate Cox regression identified 13 variables influencing HCC survival including age, HCC screening status, hepatitis C virus (HCV) status, nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) status, liver cirrhosis, elevated alpha-fetoprotein (AFP), Child-Pugh grade, tumor size, tumor number, treatment method, tumor thrombus, and extrahepatic metastasis (P<0.05). Multivariate analysis confirmed HCC screening status, tumor size, ALD, Child-Pugh classification, and therapy method as independent prognostic factors (P<0.05). The nomogram achieved an area under the ROC curve (AUC) of 0.868. Calibration curves of the 1-, 3-, and 5-year survival times and the DCA curve confirmed its predictive accuracy.</p><p><strong>Conclusions: </strong>Patients without HCC screening, tumor size >5 cm, ALD, Child-Pugh grade C, and conservative treatment had a poor survival prognosis. A nomogram based on these risk variables provides a reliable tool for predicting the survival chances of patients with HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"615-627"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093642","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>circFADS2</i> inhibits ferroptosis associated with <i>IGF2BP2</i>-dependent <i>SLC7A11</i> m6A modification in colorectal cancer cells.","authors":"Liangjun Jiang, Xianzhou Lu, Wei Li","doi":"10.21037/jgo-2024-1014","DOIUrl":"10.21037/jgo-2024-1014","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is one of the most common malignancies worldwide, and its pathogenesis is highly complex. The aim of this study was to explore the mechanism of action of <i>circFADS2</i>- and <i>IGF2BP2</i>-mediated <i>SLC7A11</i> m6A modification in CRC.</p><p><strong>Methods: </strong><i>In vitro</i> experiments were conducted to knock down <i>circFADS2</i> and overexpress <i>SLC7A11</i> in CRC cells, and <i>circFADS2</i> expression was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR); Cell Counting Kit-8 (CCK-8) and colony formation experiments were used to detect cell proliferation; cell migration was detected by Transwell; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used for detection of cell apoptosis; western blot (WB) was employed for detection of <i>SLC7A11</i> expression; the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and Fe²⁺ levels were detected; and messenger RNA (mRNA) stability testing, nuclear cytoplasmic separation experiments, RNA immunoprecipitation, fluorescence in situ hybridization (FISH), and immunofluorescence (IF) were used to verify the binding and mechanism of action of <i>circFADS2</i>, <i>IGF2BP2</i>, and <i>SLC7A11</i> mRNA. <i>In vivo</i> experiments were conducted by injecting CRC cells from each group subcutaneously into the right side of mice, and the growth of tumor cells was measured in each group <i>in vivo</i>.</p><p><strong>Results: </strong>After knocking down <i>circFADS2</i>, the expression of <i>circFADS2</i> was downregulated in CRC cells. There was a significant reduction in cell proliferation and migration and a significant increase in cell apoptosis. The expression of <i>SLC7A11</i> was significantly reduced; MDA content significantly decreased; GSH levels decreased; ROS levels increased; and the concentration of Fe²⁺ significantly increased. After <i>circFADS2</i> knockdown, the growth of CRC cells <i>in vivo</i> was inhibited. In addition, mRNA stability testing showed that <i>circFADS2</i> knockdown significantly reduced the stability of <i>SLC7A11</i> mRNA. The nuclear cytoplasmic separation experiment showed that <i>circFADS2</i> was mainly expressed in the cytoplasm. RNA immunoprecipitation indicated a binding relationship between <i>IGF2BP2</i> and <i>circFADS2</i>, as well as between <i>IGF2BP2</i> and <i>SLC7A11</i> mRNA. The results of FISH and IF analysis showed that <i>circFADS2</i>, <i>IGF2BP2</i>, and <i>SLC7A11</i> mRNA were co-localized with <i>IGF2BP2</i> in the cytoplasm.</p><p><strong>Conclusions: </strong><i>circFADS2</i> facilitates the formation of the <i>circFADS2</i>/<i>IGF2BP2</i>/<i>SLC7A11</i> mRNA-protein complex, thereby enhancing the m6A methylation of <i>SLC7A11</i>. This process significantly promotes ferroptosis in CRC cells.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"503-516"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093966","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":"Comprehensive genomic profiling of small bowel adenocarcinoma with liver metastasis.","authors":"Ruixia Jie, Changchao Xiao, Li Wang, Dejian Gu, Yuange He, Leonardo S Lino-Silva, Keita Kai, Chuanchuan Li, Fang Peng","doi":"10.21037/jgo-2025-131","DOIUrl":"10.21037/jgo-2025-131","url":null,"abstract":"<p><strong>Background: </strong>Small bowel adenocarcinoma (SBA) is a malignant tumor with a relatively low prevalence. Metastasis, especially liver metastasis (LM), is an important prognostic indicator of poor prognosis in patients with SBA. Due to the rarity of SBA, there is currently a lack of research on the characteristics of liver metastases in small intestine cancer. The aim of this study is to investigate the molecular characteristics associated with metastasis in SBA and to explore the specific molecular combinations related to LM.</p><p><strong>Methods: </strong>A retrospective study was performed on patients with SBA who were admitted to Zhejiang Hospital and Affiliated Hangzhou First People's Hospital from July 2013 to July 2022. Sequencing with tissue was performed using a 1,021-gene panel. The least absolute shrinkage and selection operator (LASSO) algorithm was used to identify the genes for predicting LM from SBA.</p><p><strong>Results: </strong>A total of 97 patients with SBA, including 48 patients without metastasis, 29 with LM, and 20 with extrahepatic metastasis (EHM), were enrolled in this cohort. The five genes with the highest mutation frequency in the overall samples were <i>TP53</i>, <i>KRAS</i>, <i>APC</i>, <i>CDKN2A</i>, and <i>SMAD4</i>, with 176 actionable mutations that had potential impact on therapy being detected in 77 (79%) cases. <i>TP53</i> was significantly more frequently mutated in the LM than in the non-LM (NLM) groups. Nine genes were selected via LASSO regression to construct the LM prediction model, which generated an area under curve of 0.867. The receiver operating characteristic (ROC) curve for the validation cohort was 0.724.</p><p><strong>Conclusions: </strong>This study elucidated the molecular characteristics of metastatic SBA and found that <i>TP53</i> mutations were associated with LM in SBA. These results deepen our understanding of the occurrence and development of SBA and the potential mechanisms of LM in SBA.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"404-414"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093635","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":"Is radix ligation of the inferior mesenteric artery effective in Japanese-Style D3 radical lymph node dissection for sigmoid colon and rectal cancer surgery?-a single-center retrospective analysis since 2002.","authors":"Takayuki Tajima, Masaya Mukai, Kyoko Kishima, Lin Fung Chan, Kazutake Okada, Shigeo Higami, Daiki Yokoyama, Syuji Uda, Sayuri Hasegawa, Hiroyasu Makuuchi","doi":"10.21037/jgo-24-815","DOIUrl":"10.21037/jgo-24-815","url":null,"abstract":"<p><strong>Background: </strong>The Japanese treatment guidelines recommend treatment of the root of the inferior mesenteric artery (IMA) (#253) to ensure ligation and dissection of the root of the IMA (#253) in descending colon cancer/sigmoid colon cancer deeper than in T2 [muscularis propria (MP)] cancer. However, #253 complete D3 dissection with IMA root ligation has been reported to increase postoperative complications, such as colonic ischemia, and to have a worse prognosis compared to IMA-preserving D3 system dissection. Therefore, we decided to compare complete IMA dissection with ligation and dissection of the IMA root and preserving the left colonic artery (LCA) preserving group.</p><p><strong>Methods: </strong>A total of 172 patients with stage II/III primary sigmoid colorectal cancer who had undergone radical curative resection were categorized into two groups: the IMA root ligation group (#253 complete D3 dissection group) and the LCA preservation group (94/78 cases), in which the IMA root was preserved and either lymph node sampling dissection or peripheral ligation of the left colorectal artery bifurcation was performed. The 5-year recurrence-free survival (5Y-RFS) and 5-year overall survival (5Y-OS) rates were compared.</p><p><strong>Results: </strong>The overall 5-year follow-up rate was 70.23%. 5Y-RFS and 5Y-OS were tested, and no significant differences were found. Similarly, there were no significant differences in the background factors. In the laparotomy/hand-assisted laparoscopic surgery (HALS)/laparoscopic surgery procedure, complete IMA ligation tended to be more common in the HALS group, whereas LCA preservation tended to be more prevalent in the laparoscopic surgery group. There were no significant differences in the postoperative complications between the groups. Anastomotic failure occurred in 6/3 patients in the IMA complete ligation/LCA preservation groups; bowel obstruction in 5/4; wound infection in 10/5; posterior hemorrhage in 1/4; dysuria in 5/1; and urinary tract infection (including cystitis) in 2/1. Postoperative cerebral infarction, ureteral injury, and thigh paresthesia were each observed in only one case in the complete ligation group.</p><p><strong>Conclusions: </strong>These results showed no significant differences in the 5Y-OS or 5Y-RFS. There was no significant difference in prognosis between patients with and without lymph node dissection at the root of the IMA. Thus, there was no significant difference in prognosis between the complete IMA ligation and LCA preservation groups, with or without IMA dissection. There were no significant differences in complications in the complete ligation group; however, the number of cases seemed large. These results suggest that preservation of the IMA may be safe and effective for stage II/III lymph node dissection in primary sigmoid colorectal cancer.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"591-598"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093739","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 dose adjustment for fruquintinib in the third-line treatment of metastatic colorectal cancer: a retrospective study with real-world settings.","authors":"Qun Zhang, Haiqing Niu, Ke Cheng, Xiaoping Qian","doi":"10.21037/jgo-2024-881","DOIUrl":"10.21037/jgo-2024-881","url":null,"abstract":"<p><strong>Background: </strong>Fruquintinib, a standard third-line treatment option for metastatic colorectal cancer (mCRC), has been shown to significantly prolong both overall survival (OS) and progression-free survival (PFS) in patients. However, we have observed that the standard dosing of fruquintinib is frequently associated with a higher incidence of adverse effects within the Chinese population, leading some patients-particularly elderly individuals-to be unable to tolerate it. This study presents a retrospective analysis to evaluate the therapeutic efficacy and safety of adjusting the administration frequency of fruquintinib in patients with mCRC.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of the follow-up data and clinicopathological characteristics of 99 patients with mCRC who were treated with an adjusted frequency of furquinitinib administration at our center. We conduct regular imaging follow-ups and tumor marker evaluations to assess the therapeutic efficacy in patients. PFS data are collected through these assessments, while OS and adverse effects information is obtained via structured telephone follow-ups.</p><p><strong>Results: </strong>There were 99 patients with mCRC treated with fruquintinib monotherapy at an adjusted dosing frequency. The median progression-free survival (mPFS) for the 99 patients on fruquintinib monotherapy was 4.1 months and the median overall survival (mOS) was 11.4 months following the adjustment of dosing frequency, the overall response rate (ORR) was 2.0%, and the disease control rate (DCR) was recorded at 40.4% within the fruquintinib monotherapy. Overall, after receiving oral administration of fruquintinib at the modified frequency, no grade 3 or higher adverse reactions occurred in all patients.</p><p><strong>Conclusions: </strong>Our results showed that the administration of fruquintinib at an adjusted dosing frequency has not significantly impacted the efficacy while demonstrating a favorable safety profile. However, this conclusion necessitates further validation through prospective clinical trials with a larger sample size.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"542-548"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093747","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":"KCNC3 as a prognostic indicator and a predictive marker for immunotherapy in colorectal cancer.","authors":"Quanqing Li, Jiaying Lv, Hongxia Duan, Pingping Sun, Bing Lu, Wenyu Shi, Yihong Cai","doi":"10.21037/jgo-24-718","DOIUrl":"10.21037/jgo-24-718","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a heterogeneous disease that is associated with several genetic or somatic mutations. Cancer immunotherapy has become a novel and revolutionary method of treatment for patients with advanced tumors. However, effective biomarkers that can reflect the response of CRC patients to immunotherapy have still not been identified. Our study aimed to explore the expression and functional role of KCNC3 in CRC.</p><p><strong>Methods: </strong>The correlation between KCNC3 expression levels and CRC progression was explored and validated using data from The Cancer Genome Atlas (TCGA) and patient's samples from the Affiliated Hospital of Nantong University. Univariate and multivariate Cox regression models were developed to determine the predictive value of KCNC3 on the prognosis and immune activation of patients with CRC. We predicted the immunotherapy response in both the high and low KCNC3 expression subgroups. Finally, we confirmed that KCNC3 promotes the proliferation and invasion of colon cancer cells.</p><p><strong>Results: </strong>In this study, data from TCGA database and clinical patient parameters showed that high KCNC3 expression was associated with tumor immune infiltration and poor prognosis of CRC. KCNC3 expression was positively correlated with the infiltration levels of CD4⁺ cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs), which contributed to the formation of an immunosuppressive tumor microenvironment (TME). The high expression of KCNC3 was accompanied by the upregulation of immune checkpoint molecules, including PDCD1, LAG3, FOXP3, and CTLA4, which stimulated tumor cells to evade immune surveillance. <i>In vitro</i> experiment, KCNC3 knockdown inhibited the growth and metastasis of SW1116 cells.</p><p><strong>Conclusions: </strong>This study demonstrated that the high expression of KCNC3 contributes to the growth and invasion of CRC and confers with immunosuppressive microenvironment that can promote tumor progression and can be used to predict the poor clinical outcome of CRC patients.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"453-469"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093751","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":"Prognostic nomogram for T3-T4 primary colorectal cancer patients with perineural invasion after surgery: a Surveillance, Epidemiology, and End Results program database analysis.","authors":"Hui Wu, Xue Liu, Haitao Chen, Qinghua Yao","doi":"10.21037/jgo-24-709","DOIUrl":"10.21037/jgo-24-709","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a common malignancy, with T3-T4 primary CRC characterized by perineural invasion (PNI), representing an aggressive subtype with poor prognosis. This study aimed to develop and validate prognostic nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with T3-T4 primary CRC and PNI after surgery.</p><p><strong>Methods: </strong>Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on patients diagnosed with T3-T4 primary CRC and PNI between 2000 and 2019. Eligible patients were randomly divided into training and validation cohorts. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors, which were integrated into nomograms for OS and CSS. The nomograms were assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>A total of 7,808 patients met the inclusion criteria. Significant prognostic factors identified in the multivariate analysis included age, sex, race, marital status, site, Tumor (T) stage of the Tumor, Node, Metastasis (TNM) staging system, radiation, regional node positive, liver and lung metastasis, tumor size, histologic type, median household income, and SEER summary stage. The nomograms exhibited good predictive accuracy, with C-indexes of 0.7422 for OS in the training cohort and 0.7428 in the validation cohort. The nomograms were validated using ROC curves, calibration plots, and DCA, which confirmed the models' reliability and clinical utility.</p><p><strong>Conclusions: </strong>The developed nomograms are robust tools for predicting 3-, 5-, and 10-year OS and CSS in patients with T3-T4 primary CRC and PNI after surgery. These tools help clinicians create personalized treatment plans and improve patient outcomes.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"549-567"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093915","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}