Journal of Gastrointestinal Cancer最新文献

{"title":"Multidisciplinary Management of Anorectal Melanoma: a Retrospective Analysis of Surgical and Systemic Therapies from the National Cancer Database.","authors":"Richard Sassun, Annaclara Sileo, Jyi Cheng Ng, Davide Ferrari, Matthew S Block, William R G Perry, Nicholas P McKenna, Kristen K Rumer, David W Larson","doi":"10.1007/s12029-025-01234-8","DOIUrl":"https://doi.org/10.1007/s12029-025-01234-8","url":null,"abstract":"<p><strong>Purpose: </strong>Anorectal melanoma (ARM) represents a problematic scenario due to a 5-year overall survival (OS) rate below 20% and its increasing incidence. Due to its comparable OS, local surgery (LS) has replaced radical surgery (RS). Adjuvant chemotherapy (Adj-CHT) and adjuvant immunotherapy (Adj-IT) are common treatments for ARM, while neoadjuvant immunotherapy (Neo-IT) has not been investigated yet. This study aimed to determine the best treatment to improve the OS.</p><p><strong>Methods: </strong>Patients with non-metastatic ARM in the National Cancer 1Database (2011-2021) who underwent surgery and received Neo-IT, Adj-IT, or Adj-CHT were included. Two cohorts were created based on the surgical approach (LS or RS). In their respective cohorts, patients receiving Neo-IT, Adj-IT, or Adj-CHT were matched 1:1:1 based on age, tumor size and location, lymphovascular invasion, and nodal disease. Kaplan-Meier analyses compared the different groups' influence on the 3-year OS.</p><p><strong>Results: </strong>Sixty patients were included in the LS cohort. Among them, there was no difference in the 3-year OS at the Kaplan-Meier analysis (Neo-IT 61%, Adj-IT 47.1%, and Adj-CHT 44%). Thirty-six patients were included in the RS cohort. Kaplan-Meier analysis for this group revealed that Neo-IT was a protective factor for 3-year OS (Neo-IT 71%, Adj-IT 11%, Adj-CHT 8%; p-value = 0.002).</p><p><strong>Conclusion: </strong>Neo-IT + RS seems to improve the 3-year OS compared to the other common treatments for ARM. Neo-IT + RS can be considered a valuable treatment since prospective trials are challenging for rare diseases. When RS is not feasible, Neo-IT + LS may be beneficial as the 3-year OS reaches 61%.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"108"},"PeriodicalIF":1.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015196","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":"The Efficacy and Safety of Nivolumab Combined with Nab-Paclitaxel or Oxaliplatin as a First-Line Treatment for Advanced or Metastatic Gastric Cancer and Gastroesophageal Junction Cancer.","authors":"Juan Li, Shuman Li, Ying Zhang, Sisi Ye, Rongrui Liu, Weiwei Shi","doi":"10.1007/s12029-025-01211-1","DOIUrl":"https://doi.org/10.1007/s12029-025-01211-1","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to assess the therapeutic efficacy and safety of nivolumab combined with chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, specifically comparing the outcomes of oxaliplatin-based versus albumin-bound paclitaxel (nab-paclitaxel)-based therapies.</p><p><strong>Methods: </strong>We retrospectively analyzed 93 patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma treated at the First Medical Center of Chinese PLA General Hospital from September 2017 to November 2022. Patients were categorized into the nivolumab + oxaliplatin (N-OX group) or nivolumab + nab-paclitaxel (N-AP group) based on the chemotherapy regimen. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated as endpoints.</p><p><strong>Results: </strong>At the end of the follow-up period on September 31, 2023, we reported an ORR of 65.6% and DCR of 95.7% across all patients. The median PFS was 8.4 months, with no significant difference between the N-OX and N-AP groups (median, 7.8 vs 9.5 months; P = 0.450). Notably, patients with diffuse gastric cancer in N-AP group showed a 44.7% reduction in tumor progression risk compared with the N-OX group (P = 0.046). The overall safety profile was acceptable in two groups.</p><p><strong>Conclusions: </strong>Our study suggested that nivolumab combined with chemotherapy was effective and safe as a first-line intervention for advanced gastric cancer. While both oxaliplatin and nab-paclitaxel regimens showed similar efficacy, the nab-paclitaxel may offer additional benefits for patients with diffuse gastric cancer. Further research is encouraged to confirm these findings and refine treatment strategies.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"109"},"PeriodicalIF":1.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029447","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":"Can Chemotherapy Facilitate Less Morbid Surgery in Multicentric Intra-abdominal Inflammatory Myofibroblastic Tumor?","authors":"Devesh S Ballal, Poonam Panjwani, Samreen S Qureshi, Sajid S Qureshi","doi":"10.1007/s12029-025-01230-y","DOIUrl":"https://doi.org/10.1007/s12029-025-01230-y","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory myofibroblastic tumor is a rare benign neoplasm affecting young adults and children. Although often considered benign, its locally aggressive nature and tendency to recur make its management immensely challenging, particularly without robust evidence to guide treatment. Surgical excision offers the best hope for a cure; however, this can lead to significant morbidity and may not always be possible, especially for multicentric diseases.</p><p><strong>Case presentation: </strong>We report a multicentric abdominal inflammatory myofibroblastic tumor in a 6-year-old girl who presented with massive abdominal distention. The sheer size of the mass, coupled with multicentric presentation and absent mobility on clinical examination, would have led to a very morbid surgical exploration. This patient was treated with initial chemotherapy, which led to a dramatic response in both symptoms and size of masses, facilitating a complete surgical resection with negligible postoperative morbidity.</p><p><strong>Conclusions: </strong>Although surgery is the preferred treatment for a resectable disease, initial chemotherapy for multicentric or locally advanced inflammatory myofibroblastic tumors facilitates complete surgical resection.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"107"},"PeriodicalIF":1.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024001","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":"Pancreatic Acinar Cell Carcinoma: Demographics, Treatment, and Survival Outcomes, A Retrospective Population-Based Study.","authors":"Abdul Qahar Khan Yasinzai, Asif Iqbal, Diego Olavarria-Bernal, Kalyani Ballur, Agha Wali, Shalini Ballur, Bisma Tareen, Marjan Khan, Hritvik Jain, Israr Khan, Nooran Fadhil, Amir Humza Sohail, Asad Ullah","doi":"10.1007/s12029-025-01233-9","DOIUrl":"https://doi.org/10.1007/s12029-025-01233-9","url":null,"abstract":"<p><strong>Purpose: </strong>Pancreatic acinar cell carcinoma accounts for 1-2% of pancreatic tumors, with increasing frequency in recent years, and still represents a poor prognosis. This study aims to expand and update existing literature by analyzing national data gathered over almost two decades.</p><p><strong>Methods: </strong>Data from 488 patients diagnosed with PACC in the Surveillance, Epidemiology, and End Results database were analyzed. This study employed the Cox regression method to compute hazard ratios and identify independent factors influencing survival. Additionally, Kaplan-Meier survival curves were utilized alongside the log-rank test.</p><p><strong>Results: </strong>The median age was 64.7 years with male predilection (70.5%). \"Poorly differentiated carcinoma\" was the most common subtype (45.8%). The liver was the most common site of metastases (31.3%). The 5-year observed overall survival (OS) rate was 19.2% (95% CI, 14.9-23.8). The 5-year cause-specific survival (CSS) rate was 22.4% (95% CI, 17.7-27.5). Male gender has a 5-year OS of 19.2% (95% CI, 14.0-25.1) compared to female OS of 30.2% (95% CI, 20.7-40.1). Patients treated with multimodal therapy (surgery with chemoradiation) over only surgery or chemotherapy had better 5-year OS, 53.5% (95% CI, 31.8-71.0). Age > 60 and distant stage were independent factors associated with increased mortality.</p><p><strong>Conclusion: </strong>Pancreatic acinar cell carcinoma is a rare, aggressive form of pancreatic cancer that primarily affects older adults. Our findings offer valuable insights to guide future clinical guidelines and tailored treatment strategies.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"106"},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024274","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":"Homologous Recombination Deficiency Is Associated with Shorter Survival in Colorectal Cancer Patients.","authors":"Xuan Zhang, Pan Zhang, Hua Dong, Lin Li, Lingling Lu, Hongyuan Lv, Xin Yu, Hong Yu","doi":"10.1007/s12029-025-01231-x","DOIUrl":"https://doi.org/10.1007/s12029-025-01231-x","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) patients benefit more from immune checkpoint inhibitor therapy, but they only account for around 15% of all patients. The remaining patients still lack effective therapeutic biomarkers to predict their prognosis.</p><p><strong>Methods: </strong>We performed whole-exome sequencing (WES) to analyze 84 CRC specimens, classifying them into different groups based on their microsatellite status (MS), tumor mutation burden (TMB), homologous recombination deficiency (HRD) score, and clinicopathological features, which might be associated with clinical outcomes. Survival analysis and multivariable Cox regression modeling were employed to identify prognostic indicators. Comparative genomic profiling evaluated somatic mutations, copy number variations (CNVs), and pathway activation patterns across clinical subgroups.</p><p><strong>Results: </strong>The characteristics of the cohort (N = 84) revealed a median age of 52 years, with a male predominance (61.9%) and a majority of patients presenting with stage IV disease (77%). The HRD-high (HRD-H) subgroup accounted for 16.7%, while 19.0% of cases were microsatellite instability-high (MSI-H) and 22.6% were TMB-high (TMB-H). Multivariable analysis identified HRD-H as an independent predictor of overall survival (OS: HR = 0.19, 95% CI 0.12-0.94, p = 0.002). Comparative genomics demonstrated distinct mutation landscapes between HRD-H and HRD-low subgroups. In microsatellite-stable (MSS) patients, HRD-H status correlated with enriched SMAD4 mutations (p < 0.01) and differential activation of TGF-β/MYC signaling pathways compared to HRD-H-MSI counterparts.</p><p><strong>Conclusion: </strong>HRD status serves as a novel independent prognostic biomarker in CRC. Our multi-parametric genomic framework delineates stratification-specific molecular signatures, advocating for HRD-integrated molecular diagnostics to optimize CRC management.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"105"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974664","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":"Immune-Based Therapies in Pancreatic Cancer: a Systematic Review of Ongoing Clinical Trials (2020-2022).","authors":"Justine T Hung, Ritwick S Mynam, Monica A Patel, Stanley Ozogbo, Noelle K LoConte, Jeremy D Kratz","doi":"10.1007/s12029-025-01194-z","DOIUrl":"https://doi.org/10.1007/s12029-025-01194-z","url":null,"abstract":"<p><strong>Introduction: </strong>Immune-based treatment strategies have emerged across solid organ malignancies largely with the development of immune checkpoint inhibitors. To date, these strategies have not improved clinical outcomes in pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>Here, we perform a systematic review to summarize available evidence for recent immune-based treatment strategies in PDAC. We analyze trends in activated clinical trials queried from clinicaltrials.gov in the years 2020-2022. We review study design, sponsorship, and trends in the phase of development. There is a growing emergence of multiple new classes of immune-based targets and combination strategies in early-phase development.</p><p><strong>Results: </strong>Immune-based clinical trials in PDAC are highly collaborative including primarily stakeholders in government, industry, and academic medical centers. In this period, a majority of trials have integrated a non-randomized design (83.2%), including a trend towards an increase in Phase I/II clinical trials. This analysis found a growing list of studies using combinations including inhibitors of vascular endothelial growth factors (VEGF), an expanded set of vaccine-based strategies, and the use of Bispecific T-Cell Engagers (BiTEs). Immune checkpoint inhibitors have been a mainstay of combination strategies including the use of new immune checkpoint inhibitors (CD40, TIGIT).</p><p><strong>Conclusion: </strong>Immune-based strategies in PDAC have expanded across new targets and the complexities of combinatory approaches. Integrating this work across key stakeholders remains of critical importance to improve clinical outcomes.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"103"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011100","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":"Advances and Challenges in the Application of Novel Oral Anticoagulants for Venous Thromboembolism Prevention Following Colorectal Cancer Surgery.","authors":"Yang Kun, Zhao Song","doi":"10.1007/s12029-025-01232-w","DOIUrl":"https://doi.org/10.1007/s12029-025-01232-w","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is a common but severe complication following colorectal cancer (CRC) surgery. Traditional anticoagulants such as low molecular weight heparin (LMWH) and vitamin K antagonists face limitations in clinical due to requirements for frequent monitoring, subcutaneous administration, and poor patient adherence. Novel Oral Anticoagulants (NOACs), with advantages including oral administration, stable pharmacokinetics, and no requirement for routine monitoring, have emerged as potential alternatives for postoperative VTE prophylaxis.</p><p><strong>Methods: </strong>This narrative review synthesized evidence from PubMed and Web of Science (up to October 2024). Initial plans for a systematic review were adjusted due to limited CRC-specific trials, focusing instead on bridging existing evidence to emerging clinical applications.</p><p><strong>Results: </strong>Postoperative VTE incidence remains heterogeneous, influenced by symptom-driven versus systematic detection and temporal improvements in perioperative care. Extended LMWH reduces VTE risk, yet adherence remains low. The PROLAPS II trial demonstrated rivaroxaban's efficacy in reducing VTE after laparoscopic CRC surgery, with comparable major bleeding rates to placebo. Meta-analyses confirm NOACs' non-inferiority to LMWH for short-term prophylaxis, but CRC-specific extended regimens lack validation. Safety concerns include heightened gastrointestinal/genitourinary bleeding risks and potential drug interactions with anticancer therapies. Clinician familiarity gaps and patient resistance to injectable agents further impede guideline adherence. Conflicting guidelines underscore unresolved debates on ideal regimens.</p><p><strong>Conclusion: </strong>NOACs offer practical advantages over LMWH for extended thromboprophylaxis in CRC surgery, particularly in enhancing adherence. However, bleeding risks and limited high-quality evidence necessitate cautious clinical integration. Future research must prioritize large-scale RCTs to validate LMWH-NOAC sequential regimens, optimize risk-stratified protocols, and address interactions within enhanced recovery pathways. Harmonized guidelines and provider education are critical to bridging implementation gaps.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"104"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028371","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":"Effects of Palliative Esophageal External Beam Radiation Therapy in Patients with Stent for Esophageal Cancer: A Retrospective Cohort Study.","authors":"Emily Adams, Héloïse Lavoie-Gagnon, Farhana Islam, Michael Humer, Benjamin Mou, Theodora A Koulis, David Kim, Siavash Atrchian","doi":"10.1007/s12029-025-01228-6","DOIUrl":"https://doi.org/10.1007/s12029-025-01228-6","url":null,"abstract":"<p><strong>Purpose: </strong>Self-expandable metallic stents (SEMS) provide immediate but nondurable dysphagia relief in esophageal cancer, while external beam radiotherapy (EBRT) provides slower, more durable dysphagia relief. While the combination of SEMS with EBRT would seem to offer both rapid and durable dysphagia relief in the palliative setting, there remains controversy on its safety and efficacy. We investigated patient outcomes regarding EBRT after SEMS placement in patients with incurable esophageal cancer at a regional Canadian cancer program.</p><p><strong>Methods: </strong>We conducted a single-centre retrospective chart review from January 2010 to July 2020 to compare stent-related complications and survival in patients with incurable esophageal cancer treated with SEMS alone or SEMS + EBRT at Kelowna General Hospital.</p><p><strong>Results: </strong>66 patients were included in the SEMS alone group and 26 in the SEMS + EBRT group. Patients treated with SEMS alone showed an average of 3.05 fewer stent-related complications compared to patients who received SEMS + EBRT. The SEMS alone group also had 9.05 greater odds of experiencing higher grade complications compared to the SEMS + EBRT group (p < 0.001). Patients in the SEMS + EBRT group survived significantly longer than those treated with SEMS alone, with a median overall survival of 163.5 days and 65 days, respectively.</p><p><strong>Conclusions: </strong>SEMS monotherapy was associated with significantly fewer, yet higher grade stent-related complications compared to palliative EBRT after SEMS placement. SEMS + EBRT treatment was associated with significantly prolonged survival compared to SEMS alone. Prospective studies are needed to confirm these findings.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"102"},"PeriodicalIF":1.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969922","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":"Surgical Resection Versus Microwave Ablation for Colorectal Liver Oligometastases: A Multicenter Cohort Study of 1027 Patients.","authors":"Bin Li, Lei Li, He Ren","doi":"10.1007/s12029-025-01222-y","DOIUrl":"https://doi.org/10.1007/s12029-025-01222-y","url":null,"abstract":"<p><strong>Background: </strong>The choice between surgical resection (SR) and microwave ablation (MWA) as first-line treatments that prolong survival duration for colorectal liver oligometastases (CRLOM) remains controversial.</p><p><strong>Objective: </strong>This study aimed to compare survival outcomes, therapeutic parameters, and safety between SR and MWA in patients with CRLOM.</p><p><strong>Methods: </strong>From January 2012 to December 2022, we identified 1027 eligible patients with CRLOM who underwent either SR (n = 464) or MWA (n = 563) as hepatic local-region treatment. The cumulative 1-, 3-, 5-, and 8-year overall survival (OS) and progression-free survival (PFS) rates between the two modalities were compared using the Kaplan-Meier method with the log-rank test. The propensity score matching (PSM) method was used to improve the selective bias. Univariate and multivariate analyses of clinicopathological variables were conducted to identify risk factors affecting long-term survival.</p><p><strong>Results: </strong>After PSM, all baseline variables were balanced between the SR (n = 393) and MWA groups (n = 393). After a median follow-up of 39.8 months, no significant differences in the long-term survival outcomes were observed between the two groups (median OS time, MWA: 70.6 months vs. SR: 83.2 months; P = 0.124; median PFS time, MWA: 18.5 months vs. SR: 22.3 months; P = 0.680). PSM-adjusted analyses revealed similar results. The presence of 3-5 intrahepatic nodules (hazards ratio [HR] 1.65; 95% CI 1.31-2.06; P < 0.001) and SR (HR 1.28; 95% CI 1.11-1.69; P = 0.028) were independent prognostic risk factors for OS. A significant interaction effect of therapeutic modality and age, pathological differentiation, diameter, and number was observed (P = 0.039, 0.004, 0.031, and 0.032).</p><p><strong>Conclusions: </strong>MWA offers comparable long-term survival benefits to SR for patients with CRLOM.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"101"},"PeriodicalIF":1.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969109","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":"Identification of Novel Protein Biomarkers for Intrahepatic Cholangiocarcinoma by Integrating Human Plasma Proteome with Genome.","authors":"Yu-Sen Chen, Wei-Bang Yang, Yi-Hu Li, Jin-Yang Xu, Yu-Xuan Wei, Si-Min Huang, Xiao-Feng Jiang, Jian-Hui Li","doi":"10.1007/s12029-025-01226-8","DOIUrl":"https://doi.org/10.1007/s12029-025-01226-8","url":null,"abstract":"<p><strong>Background: </strong>The proteome serves as a key source for the discovery of therapeutic targets. This study utilized proteome-wide Mendelian randomization (MR) to identify protein biomarkers potentially associated with intrahepatic cholangiocarcinoma (ICC).</p><p><strong>Methods: </strong>We derived protein quantitative trait loci (pQTLs) from the deCODE plasma proteome GWAS and genetic ICC associations from a European meta-analysis. Proteome-wide MR identified candidate proteins linked to ICC risk. Expression of MR-identified biomarkers in the plasma of ICC patients was detected by ELISA. ScRNA-seq analysis detected the specific cell type with enrichment expression. Prognostic and diagnostic evaluations in ICC of these proteins were performed using samples derived from TCGA and GTEx databases.</p><p><strong>Results: </strong>MR analysis genetically predicted 5 proteins were associated with ICC risk (STX12, A2M, CD163, CXADR and FOXJ2). The results of the MR analysis for the five identified targets were consistent with the measured plasma concentrations of these targets in ICC patients and healthy volunteers. The differential RNA-seq analysis between tumor and adjacent normal tissues showed that STX12 was expressed at higher levels in tumor tissues, while A2M, CXADR, CD163, and FOXJ2 were expressed at higher levels in adjacent normal tissues. ScRNA-seq analysis revealed that these protein-coding genes are mainly expressed in TAMs, TEC, HPC-like cells and malignant cells in ICC tumor tissue. Prognosis analysis showed higher CXADR expression correlated with longer OS in CHOL (P = 0.041). The AUC for A2M, CD163, CXADR, FOXJ2, and STX12 were 0.975, 0.705, 0.917, 0.997, and 0.956, respectively.</p><p><strong>Conclusion: </strong>This study represents the first Proteome-MR analysis of ICC, revealing its complex genetic architecture and identifying five novel blood proteins with potential causal links to the disease. Through proteome-MR analysis, scRNA-seq analysis, and diagnostic-prognostic evaluation using TCGA and GTEx databases, these proteins were assessed as promising therapeutic and diagnostic targets. The findings provide a theoretical foundation for future ICC treatment strategies.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"56 1","pages":"100"},"PeriodicalIF":1.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988355","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}