Journal of Gastrointestinal Cancer最新文献

{"title":"Gender, Race, and Regional Disparities in Leading Authorships of Gastroenterology and Hepatology Randomized Controlled Trials.","authors":"Subhash Chander, Fnu Sorath, Yaqub Nadeem Mohammed, Om Parkash, Fnu Sadarat, Abhi Chand Lohana, Sheena Shiwlani","doi":"10.1007/s12029-024-01161-0","DOIUrl":"10.1007/s12029-024-01161-0","url":null,"abstract":"<p><strong>Background and aims: </strong>To investigate gender, racial, ethnic, and regional disparities in first and senior authorship positions in gastroenterology/hepatology-related randomised controlled trials (RCT).</p><p><strong>Method: </strong>Retrospective bibliometric analysis of PubMed-indexed RCTs published between January 2000 to December 2022 in leading journals with an impact factor of at least five.</p><p><strong>Results: </strong>943 RCTs met our inclusion criteria, providing a participant pool of 301 female (15.96%) and 1,585 male (84.04%) authors from 37 countries (70% high-income countries). Despite a significant increase in the proportion of female authors in first and senior authorship positions between 2000 and 2022 (p<0.001), females were grossly underrepresented in both authorship positions, with a male-to-female ratio of 4.45 and 6.37, respectively. The male-to-female ratio was highest among Asian authors (7.79) than among White (4.22), Hispanic (1.44), and Black (1) authors in the first authorship position. In contrast, the male-to-female ratio was similar for Asian (6.2) and White (6.67) authors in the senior authorship position, with a low underlying frequency of Hispanic and Black female authors.</p><p><strong>Conclusion: </strong>Despite significant improvements in gender, racial and ethnic representation in first and senior authorship of gastroenterology/hepatology-related RCTs published in high-impact journals, progress toward parity remains slow. Targeted interventions to improve author diversity are warranted.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"34"},"PeriodicalIF":1.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demographics, Prognostic Factors, and Survival Outcomes in Hepatic Angiosarcoma: A Retrospective Analysis.","authors":"Agha Wali, Jaylyn Robinson, Asif Iqbal, Abdul Qahar Khan Yasinzai, Amir Humza Sohail, Hritvik Jain, Nooran Fadhil, Marjan Khan, Israr Khan, Nabin R Karki, Asad Ullah","doi":"10.1007/s12029-024-01157-w","DOIUrl":"https://doi.org/10.1007/s12029-024-01157-w","url":null,"abstract":"<p><strong>Background: </strong>Hepatic angiosarcoma (HA) is a rare malignant vascular neoplasm. Currently, there are no standardized protocols for treating HA. This study aims to understand clinicopathologic analysis, prognostic factors, and treatment outcomes comprehensively.</p><p><strong>Methods: </strong>The data retrieved from the SEER database was reviewed for hepatic angiosarcoma cases between 2000 and 2021.</p><p><strong>Results: </strong>A total of 389 patients with hepatic angiosarcoma were identified with a mean age of 63.9 years (SD ± 16). Most patients were male (64%), and per US census data, non-Hispanic Asians or Pacific Islanders were the most common race (17%). In known cases of tumor stage (61%), the most common tumor stage was distant (22%), and most were grade III (18%) tumors. Overall, the 3-year survival rate was 6.7% with a 95% confidence interval (95% CI 0.044-0.100), disease-specific survival at a 1-year survival rate was 4.43% (95% CI 0.023-0.083), and no patients survived by 3 years. The best overall survival rate was the 1-year rate for surgical resection, 18.20% (95% CI 0.075-0.441). Chemotherapy had a 1-year survival rate of 11% (95% CI 0.057-0.211), and radiation therapy had no survival significance (p = 0.2). Multivariate analysis shows age above 70 years (H.R. 1.67 (95% CI 1.181-2.381), p < 0.05), no surgical intervention (H.R. 2.29 (95% CI 1.585-3.336) p < 0.001), and distant stage (H.R. 2.54 (95% CI 1.696-3.805) p < 0.001) are negative prognostic factors, whereas female sex (H.R. 0.68 (95% CI 0.536-0.875) p < 0.05) is a positive prognostic factor.</p><p><strong>Conclusion: </strong>Increasing age (> 70 years), male sex, and distant stage were found to be strong predictors of poor survival outcomes. Patients had better outcomes when surgical resection and chemotherapy were included in their treatment. These results can provide continued evidence in the future management of patients with hepatic angiosarcoma.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"33"},"PeriodicalIF":1.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of Understaging with EUS and PET-CECT in Early Esophageal Carcinoma.","authors":"Karthik Venkataramani, Sabita Jiwnani, Devayani Niyogi, Virendrakumar Tiwari, C S Pramesh, George Karimundackal","doi":"10.1007/s12029-024-01147-y","DOIUrl":"10.1007/s12029-024-01147-y","url":null,"abstract":"<p><strong>Background: </strong>The clinicoradiological staging for esophageal cancer is fraught with variable accuracy, potentially depriving patients who have been understaged of the benefit of neoadjuvant therapy, which has been shown to improve long-term survival in locally advanced malignancies. It is imperative to identify these high-risk tumors for tailored treatment.</p><p><strong>Methods: </strong>Retrospective analysis of a prospective database of patients undergoing esophagectomy for carcinoma esophagus between 2011 and 2019. Patients with clinicoradiological early-stage esophageal carcinoma (T1/2 and N0), staged with EUS and fluoro-deoxy-glucose positron emission tomography with contrast-enhanced computed tomography (FDG PET-CECT), and undergoing upfront surgery were included. Demographic profile, staging, perioperative outcomes, and follow-up data were extracted from electronic records and analyzed using SPSS 26.0.</p><p><strong>Results: </strong>During this period, we performed 1496 esophagectomies, of which 68 patients (4.5%) underwent upfront surgery for early-stage tumors. The overall concordance between clinical and surgical staging was 55.8%. The positive predictive value (PPV) of EUS for T1, T2, and N0 was 81.6%, 46.7%, and 82.4%, respectively, with 10.2% and 17% upstaging to T3 and N + , respectively. On multivariate analysis, T2 on EUS and tumors longer than 3.5 cm and having standardized uptake value (SUVmax) > 3.05 on FDG PET were strong predictors of stage migration. The 3-year overall survival (OS) of the entire cohort was 74.2%, while those who were understaged had a worse outcome, with a 3-year survival of 48.2%.</p><p><strong>Conclusion: </strong>Endoscopic T2 stage, length more than 3.5 cm, and SUVmax more than 3.05 are associated with significant understaging and hence should be considered for neoadjuvant therapy.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"32"},"PeriodicalIF":1.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Patient-Reported Outcomes and Surgical Attrition During Neoadjuvant Therapy for Gastrointestinal Malignancies.","authors":"Alexander H Shannon, Marilly Palettas, Angela Sarna, Emily Huang, Peter J Kneuertz, Mary Dillhoff, Aslam Ejaz, Timothy M Pawlik, Jordan M Cloyd","doi":"10.1007/s12029-024-01153-0","DOIUrl":"https://doi.org/10.1007/s12029-024-01153-0","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant therapy (NT) is increasingly used for gastrointestinal (GI) and hepatopancreatobiliary (HPB) cancers. Risk factors for surgical attrition during NT are poorly understood. A planned secondary analysis of patient-reported outcomes (PROs) from a prospective cohort study of patients undergoing NT was performed to identify factors associated with surgical attrition.</p><p><strong>Methods: </strong>Adult patients with GI/HPB cancer receiving NT were provided a mobile phone application administering QOL assessments every 30 days and measuring mood/symptoms until NT completion. Univariate and multivariate logistic regression were performed to determine the association between demographic, clinical characteristics, and PROs with surgical attrition (no surgery (NS) versus surgery or watchful waiting (SWW)). Mixed-effects regression models evaluated trends of QOL and symptoms between the cohorts.</p><p><strong>Results: </strong>Among 104 enrolled patients, mean age was 60.5 ± 11.5 years, 57 (55%) were male, and 95 (91%) were Caucasian. After a mean duration of 3.4 months of NT, 76 (73%) patients underwent SWW, while 28 (27%) did not (NS). Cancer type (HPB vs GI, OR 7.0, CI 2.7-19.3, p < 0.001), comorbidities (OR 1.72, CI 1.0-2.99, p = 0.05), and severe complications during NT (OR 4.2, CI 1.2-15.3, p = 0.03) were associated with NS. There were no differences between longitudinal QOL scores or PROs among patients who underwent SWW versus NS except for the lack of appetite, which was associated with NS (OR 3.6, CI 1.0-12.2, p = 0.04).</p><p><strong>Conclusions: </strong>Among patients undergoing NT for GI/HPB malignancies, type of cancer, comorbidities, and severe complications during NT were associated with failure to undergo surgery, whereas QOL and PROs were largely not.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"31"},"PeriodicalIF":1.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed Surgery after Neoadjuvant Short-course Radiation for Rectal Cancer Improves Pathologic Outcomes without Impacting Survival: A National Cancer Database Analysis.","authors":"Praachi Raje, Hiroko Kunitake, Christy E Cauley, Robert N Goldstone, Grace C Lee, Rocco Ricciardi","doi":"10.1007/s12029-024-01154-z","DOIUrl":"https://doi.org/10.1007/s12029-024-01154-z","url":null,"abstract":"<p><strong>Purpose: </strong>Interval to surgery following short course radiotherapy (SCRT) for rectal cancer is not standardized. This study investigated pathologic outcomes and survival with varying intervals to surgery.</p><p><strong>Methods: </strong>Using the National Cancer Database, adults who received SCRT from 2005 to 2020 were grouped by additional neoadjuvant chemotherapy. Outcomes were analyzed for early (within 1 week) and delayed (over 4 weeks) intervals.</p><p><strong>Results: </strong>Of 1154 patients, 671 received neoadjuvant SCRT and chemotherapy (Group 1: median interval 29 days, 50% delayed) and 483 received SCRT only (Group 2: median interval 9 days, 27% delayed). In Group 1, delay was associated with tumor downstaging (OR 1.61; 95% CI, 1.03-2.51; p = 0.036), decreased lymphovascular invasion (OR 0.53; 95% CI, 0.33-0.85; p = 0.009), and complete pathologic response (OR 2.86; 95% CI, 1.06-7.76; p = 0.039). Delay was associated with decreased tumor deposits in Group 1 (OR 0.46; 95% CI, 0.30-0.71; p < 0.001) and Group 2 (OR 0.37; 95% CI 0.21-0.65; p = 0.001). Survival was not affected.</p><p><strong>Conclusion: </strong>Delaying surgery following neoadjuvant SCRT results in favorable pathologic outcomes without impacting overall survival, regardless of neoadjuvant chemotherapy.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"30"},"PeriodicalIF":1.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer.","authors":"Jingquan Jia, Ashley Moyer, Melissa Lowe, Emily Bolch, Jeremy Kortmansky, May Cho, Heinz-Josef Lenz, Aparna Kalyan, Donna Niedzwiecki, John H Strickler","doi":"10.1007/s12029-024-01156-x","DOIUrl":"10.1007/s12029-024-01156-x","url":null,"abstract":"<p><strong>Purpose: </strong>MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA.</p><p><strong>Methods: </strong>Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety.</p><p><strong>Results: </strong>Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs.</p><p><strong>Conclusion: </strong>Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"29"},"PeriodicalIF":1.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-EGFR Rechallenge in Metastatic Colorectal Cancer and the Role of ctDNA: A Systematic Review and Meta-analysis.","authors":"Luís Felipe Leite da Silva, Erick Figueiredo Saldanha, Lucas Diniz da Conceição, Mariana Macambira Noronha, Marcos Vinícius Martins Grangeiro da Silva, Renata D 'Alpino Peixoto","doi":"10.1007/s12029-024-01152-1","DOIUrl":"10.1007/s12029-024-01152-1","url":null,"abstract":"<p><strong>Background: </strong>Metastatic colorectal cancer (mCRC) remains a significant clinical challenge. While anti-EGFR inhibitors have improved survival rates, their long-term efficacy is limited by disease progression, which is often associated with the development of acquired resistance mutations. However, some patients may regain sensitivity to anti-EGFR agents after alternative therapies, suggesting a potential benefit for rechallenge strategies. Our study aims to conduct a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of EGFR rechallenge in patients with mCRC.</p><p><strong>Methods: </strong>A systematic search of the MEDLINE, EMBASE, and Cochrane databases was conducted between October 28 and December 24, 2023, to identify clinical trials investigating treatment regimens incorporating panitumumab or cetuximab as a rechallenge strategy. Pooled proportions or hazard ratios (HR) were calculated using a random effects model. Inter-study heterogeneity was assessed using the I².</p><p><strong>Results: </strong>Among the 2105 articles identified through the search, 13 met the predetermined inclusion criteria. Of these, 12 were phase II studies, encompassing 92.3% of the patient population. Cetuximab was administered to 302 patients (75.1%), whereas panitumumab was utilized in 100 patients (24.9%).A pooled analysis of eight studies demonstrated an objective response rate of 20.50% (95% CI 7.94 to 33.07) and a disease control rate of 67.35% (95% CI 58.60 to 76.09). The median progression-free survival was estimated at 3.5 months (95% CI 2.68-6.69), with a median OS of 9.8 months (95% CI 6.71-12.89). Patients exhibiting RAS wild-type status in circulating tumor DNA (ctDNA) analysis derived enhanced benefits from anti-EGFR rechallenge (HR: 0.41; 95% CI 0.28-0.60, I² = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).</p><p><strong>Conclusion: </strong>This meta-analysis underscores the efficacy and safety of anti-EGFR rechallenge as a promising therapeutic approach for a subset of patients afflicted with mCRC. The observed correlation between wild-type RAS status, as determined through ctDNA analysis, and improved OS signals the prospect of precision oncology in guiding treatment decisions.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"28"},"PeriodicalIF":1.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Vitamin Intake and Colorectal Cancer: Evidence from NHANES Data.","authors":"Man Luo, Lingyi Li","doi":"10.1007/s12029-024-01107-6","DOIUrl":"10.1007/s12029-024-01107-6","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the associations between vitamins and colorectal cancer (CRC) based on a national sample of US adults.</p><p><strong>Methods: </strong>A total of 6200 samples were collected from the National Health and Nutrition Examination Survey to explore the relationship between vitamins (specifically, A, C, and D) and CRC. Logistic regression models were employed to assess the associations between dietary vitamin intake and CRC.</p><p><strong>Results: </strong>Our findings indicate a negative association between vitamin C intake and CRC. However, the associations of vitamin A and vitamin D with CRC were not statistically significant. For vitamin C, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 0.91 (0.76-0.97) for the second tertile and 0.81 (0.64-0.95) for the third tertile (P < 0.01). Conversely, for vitamin A, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.02 (0.82-1.22) for the second tertile and 1.04 (0.75-1.25) for the third tertile (P < 0.01). For vitamin D, compared to the first tertile, the odds ratios (ORs) and 95% confidence intervals (CIs) were 0.96 (0.84-1.06) for the second tertile and 1.01 (0.83-1.15) for the third tertile (P < 0.01). Additionally, the negative association between vitamin C and CRC was more pronounced among females (0.76, 0.67-0.92), individuals aged 60 and above (0.75, 0.69-0.95), and those with a BMI > 30 (0.78, 0.67-0.93).</p><p><strong>Conclusion: </strong>Our findings suggest that higher vitamin C intake is associated with a reduced prevalence of CRC. However, further large-scale prospective cohort studies are warranted to validate our results.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1581-1587"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Intrahepatic Mesothelioma: Case Series and Systematic Review of Literature.","authors":"Junjun Jia, Xinyue Tan, Feng Gao, Zhou Shao, Min Zhang","doi":"10.1007/s12029-024-01075-x","DOIUrl":"10.1007/s12029-024-01075-x","url":null,"abstract":"<p><strong>Background: </strong>Primary intrahepatic mesothelioma (PIHMM) has been rarely reported. Its typical clinical presentation, radiological features and pathology have not been defined. Here, we aimed to summarize its diagnosis and treatment.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of three cases of PIHMM in the First Affiliated Hospital of Zhejiang University School of Medicine and reviewed the current literature to investigate the clinical and pathological characteristics and prognosis of PIHMM.</p><p><strong>Results: </strong>Based on our case series and the literature, the mean age of PIHMM was 59.7 (41-83) years. Most patients present with nonspecific symptoms such as abdominal pain, fever, weight loss and weakness. On imaging, PIHMM usually presented as a solid, heterogeneous soft tissue mass with irregular margins and significant enhancement of the margins in the arterial phase. Immunohistochemical markers such as calretinin, cytokeratin (CK)5/6, D2-40, WT-1, mesothelin CK and vimentin may be useful for diagnosis. The 3-year relapse-free survival rate (RFS) was 51.85%, the 3-year overall survival (OS) rate was 83.33% and the 3-year postoperative overall survival rate was 100%.</p><p><strong>Conclusion: </strong>PIHMM can only be diagnosed by careful postoperative pathology, because of its nonspecific clinical presentations, serological indicators or imaging features. Immunohistochemical staining is very useful to distinguish this tumor from other liver tumors. Surgery is the mainstay of treatment.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1520-1529"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Bioinformatics Analysis: Unraveling Variant Signatures and Single-Nucleotide Polymorphism Markers Associated with 5-FU-Based Chemotherapy Resistance in Colorectal Cancer Patients.","authors":"Masomeh Askari, Ebrahim Mirzaei, Leila Navapour, Mina Karimpour, Leili Rejali, Somayeh Sarirchi, Ehsan Nazemalhosseini-Mojarad, Stefania Nobili, Claudia Cava, Amir Sadeghi, Nayeralsadat Fatemi","doi":"10.1007/s12029-024-01102-x","DOIUrl":"10.1007/s12029-024-01102-x","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance in colorectal cancer (CRC) is modulated by multiple molecular factors, which can be ascertained through genetic investigation. Single nucleotide polymorphisms (SNPs) within key genes have the potential to impair the efficacy of chemotherapeutic agents such as 5-fluorouracil (5-FU). Therefore, the identification of SNPs linked to drug resistance can significantly contribute to the advancement of tailored therapeutic approaches and the enhancement of treatment outcomes in patients with CRC.</p><p><strong>Material and method: </strong>To identify dysregulated genes in 5-FU-based chemotherapy responder or non-responder CRC patients, a meta-analysis was performed. Next, the protein-protein interaction (PPI) network of the identified genes was analyzed using the STRING database. The most significant module was chosen for further analysis. In addition, a literature review was conducted to identify drug resistance-related genes. Enrichment analysis was conducted to validate the main module genes and the genes identified from the literature review. The associations between SNPs and drug resistance were investigated, and the consequences of missense variants were assessed using in silico tools.</p><p><strong>Result: </strong>The meta-analysis identified 796 dysregulated genes. Then, to conduct PPI analysis and enrichment analysis, we were able to discover 23 genes that are intricately involved in the cell cycle pathway. Consequently, these 23 genes were chosen for SNP analysis. By using the dbSNP database and ANNOVAR, we successfully detected and labeled SNPs in these specific genes. Additionally, after careful exclusion of SNPs with allele frequencies below 0.01, we evaluated 6 SNPs from the HDAC1, MCM2, CDK1, BUB1B, CDC14B, and CCNE1 genes using 8 bioinformatics tools. Therefore, these SNPs were identified as potentially harmful by multiple computational tools. Specifically, rs199958833 in CDK1 (Val124Gly) was predicted to be damaging by all tools used. Our analysis strongly indicates that this specific SNP could negatively affect the stability and functionality of the CDK1 protein.</p><p><strong>Conclusion: </strong>Based on our current understanding, the evaluation of CDK1 polymorphisms in the context of drug resistance in CRC has yet to be undertaken. In this investigation, we showed that rs199958833 variant in the CDK1 gene may favor resistance to 5-FU-based chemotherapy. However, these findings need validation in an independent cohort of patients.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":" ","pages":"1607-1619"},"PeriodicalIF":1.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}