Seminars in oncology最新文献

{"title":"Liquid biopsy: An innovative tool in oncology. Where do we stand?","authors":"Serafina Martella ,&nbsp;Demi Wekking ,&nbsp;Eleonora Lai ,&nbsp;Matteo Lambertini ,&nbsp;Angela Pettinato ,&nbsp;Alissa Parrino ,&nbsp;Francesca Semonella ,&nbsp;Giorgia Sanna ,&nbsp;Antonio Maccioni ,&nbsp;Mario Scartozzi ,&nbsp;Alfredo Addeo ,&nbsp;Cinzia Solinas","doi":"10.1016/j.seminoncol.2025.152343","DOIUrl":"10.1016/j.seminoncol.2025.152343","url":null,"abstract":"<div><div>The Liquid Biopsy (LB) represents an ideal surrogate of tumor Tissue Biopsy (TB) when the aim is to obtain useful information on patient prognosis and personalized therapy. This technique renders it possible to isolate circulating tumor cells, circulating tumor DNA and other molecules from biological fluids. The most commonly used fluid for liquid biopsy is blood, but depending on the case it could be necessary to isolate the tumor components from other biological fluids such as urine, pleural effusion, cerebrospinal fluid, and others. The main advantages of liquid biopsy are the minimally invasive nature of the procedure and the possibility of analyzing all tumor clones. Limitations include difficulties in the isolation of tumor components and the requirement for highly sensitive analysis methods to avoid the risk of technical artifacts. In our review we will focus on describing circulating tumor biomarkers to illustrate the variety of information that can be obtained from biological fluids, particularly blood. We will then discuss the advanced biotechnological techniques suitable for the identification and analysis of Circulating Tumor DNA (ctDNA), examining both the potential and limitations of analytical methods and the clinical applicability of liquid biopsy for cancer diagnosis, monitoring, and therapeutic prediction. Additionally, we will explore strategies to enhance this valuable alternative to the more invasive tissue biopsy, with a dedicated focus on ongoing clinical studies, currently approved tests, and guideline recommendations.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152343"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNAs: Emerging regulators of signaling pathways in epithelial-mesenchymal transition and angiogenesis during breast cancer progression","authors":"Nivruthi Sasi,&nbsp;Dilipkumar Preetha,&nbsp;Saranya Iyyappan,&nbsp;Nagarajan Selvamurugan","doi":"10.1016/j.seminoncol.2025.152340","DOIUrl":"10.1016/j.seminoncol.2025.152340","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) have emerged as important regulators of gene expression and cellular activities, and abnormalities in circRNAs in breast cancer have been linked to important biological processes like epithelial-mesenchymal transition (EMT) and angiogenesis, both essential for tumor metastasis. EMT facilitates the transition of epithelial cancer cells into a mesenchymal phenotype, enhancing their invasive and migratory capabilities, while angiogenesis promotes tumor progression by forming new blood vessels. CircRNAs also interact with microRNAs to regulate signaling pathways such as TGF-β, Wnt/-catenin, and VEGF. Besides EMT and angiogenesis, studies have identified that circRNAs affect metabolic reprogramming, chemoresistance, tumor microenvironment remodeling, and immunological evasion. Thus, circRNAs play a multifaceted role in the development of breast cancer. They hold potential as non-invasive biomarkers and therapeutic targets due to their high stability, resistance to exonuclease degradation, abundance in body fluids, and diverse expression patterns across different tissues. This review summarizes and critically assesses existing understanding of the functional roles and molecular processes of circRNAs in controlling EMT and angiogenesis during breast cancer progression.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152340"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the clinical trials, regulatory insights, and challenges of PROTACs in oncology","authors":"Sowndharya M ,&nbsp;Ramesh Joga ,&nbsp;Kajal Gandhi ,&nbsp;Sravani Yerram ,&nbsp;Rajeev Singh Raghuvanshi ,&nbsp;Saurabh Srivastava","doi":"10.1016/j.seminoncol.2025.152339","DOIUrl":"10.1016/j.seminoncol.2025.152339","url":null,"abstract":"<div><div>While various targeted therapies exist for cancer, resistance mechanisms remain a significant challenge. Recent advancements in cancer treatment have led to the emergence of proteolysis-targeting chimeras (PROTACs), a promising technology utilizing hetero-bifunctional molecules to target and degrade proteins implicated in cancer progression through the ubiquitin-proteasome system (UPS). PROTACs offer a novel approach, with recent studies and clinical trials demonstrating promising outcomes in degrading endogenous proteins linked to cancer. This work explores classification, regulatory approvals, and ongoing clinical trials of PROTAC technology in cancer management. It emphasizes the importance of regulatory compliance to expedite approvals from relevant authorities. It also highlights challenges and opportunities associated with their implementation. Despite these preliminary efforts, PROTACs show immense potential in effectively addressing cancer. Their ability to target specific proteins for degradation represents a significant advancement in cancer therapeutics, offering new hope for improved outcomes in patient care.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152339"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High tumor mutation burden mitigates the negative impact of chemotherapy history on immune checkpoint blockade therapy","authors":"Ming Zheng MD, PhD","doi":"10.1053/j.seminoncol.2025.01.003","DOIUrl":"10.1053/j.seminoncol.2025.01.003","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC. ICI therapy has revolutionized treatment, but prior chemotherapy may diminish ICI treatment efficacy. Tumor mutation burden (TMB) has emerged as a crucial predictor of ICI response, yet its interaction with chemotherapy history in ICI therapy is not fully understood. In this study, I investigate the impact of chemotherapy history on ICI treatment outcomes, focusing on TMB as a potential mitigating factor. Analyzing data from 512 patients with advanced NSCLC treated with PD-1/PD-L1 or CTLA-4 inhibitors, this sudy found that prior chemotherapy significantly reduced objective response rates (ORR) to ICI therapy, particularly in patients with low TMB (&lt;15 mut/Mb). However, in patients with high TMB (≥15 mut/Mb), the negative impact of chemotherapy history on ICI treatment efficacy is minimal, suggesting that high TMB mitigates chemotherapy-induced resistance to ICI therapy. Furthermore, while chemotherapy history is associated with worse overall survival (OS) and progression-free survival (PFS) following ICI therapy in low-TMB patients, no such association is observed in high-TMB patients. These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152334"},"PeriodicalIF":3.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant polyphenols in gastric cancer: Nature's healing touch","authors":"Chengu Niu ,&nbsp;Jing Zhang ,&nbsp;Patrick I. Okolo III ,&nbsp;Ebubekir Daglilar","doi":"10.1053/j.seminoncol.2025.01.002","DOIUrl":"10.1053/j.seminoncol.2025.01.002","url":null,"abstract":"<div><div>Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 2","pages":"Article 152333"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingerprint change as a consequence of anticancer treatments: A systematic integrative review","authors":"Silvia Belloni ,&nbsp;Arianna Magon ,&nbsp;Rita de Sanctis ,&nbsp;Paola Tiberio ,&nbsp;Gianluca Conte ,&nbsp;Cristina Arrigoni ,&nbsp;Rosario Caruso","doi":"10.1016/j.seminoncol.2025.152335","DOIUrl":"10.1016/j.seminoncol.2025.152335","url":null,"abstract":"<div><h3>Objective</h3><div>While it is widely acknowledged that fingerprint recognition has played an essential part in policing and forensic science, little is known about fingerprint alterations in medical science, specifically as a consequence of anticancer treatments. Thus, we aimed to analyze the extent of evidence between cancer treatments and fingerprint alterations in adults with cancer.</div></div><div><h3>Methods</h3><div>A systematic integrative review was conducted according to the PRISMA statement and the Cochrane guidelines for conducting a systematic review. PubMed, CINAHL, Web of Science, and Scopus were searched from the inception between August and November 2024. The quality appraisal was conducted to evaluate the methodological quality of the included articles, selecting the most appropriate tool based on the publication type and study design.</div></div><div><h3>Results</h3><div>Of 176 records, we selected five experimental studies articles and nine case reports publications. A correlation between specific anticancer treatments (capecitabine, taxanes, and tyrosine kinase inhibitors) and fingerprint alterations has been documented in individuals with various cancer diagnoses (mainly advanced breast and colorectal cancers). The majority of articles were of moderate to low quality.</div></div><div><h3>Conclusions</h3><div>Although fingerprint alteration as a consequence of specific anticancer treatments has been documented, further large and well-designed experimental studies are necessary to quantify the phenomenon burden in relation to specific anticancer regimens and populations.</div></div><div><h3>Prospero registration n</h3><div>(CRD42024581192).</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 41-54"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colorectal cancer in Ethiopia: Epidemiological trends, diagnostic and laboratory capacities, and challenges","authors":"Gashaw Getaneh Dagnaw ,&nbsp;Haileyesus Dejene","doi":"10.1053/j.seminoncol.2024.09.002","DOIUrl":"10.1053/j.seminoncol.2024.09.002","url":null,"abstract":"<div><div>Colorectal cancer (CRC) refers to cancer that develops in the colon or rectum, parts of the large intestine. It ranks as the third most prevalent form of cancer globally. Colorectal cancer is responsible for the morbidity of millions and the loss of hundreds of thousands of lives worldwide although the incidence varies significantly depending on geographical location. In recent years, CRC has decreased in high-income countries due to technological advancements in diagnosis and treatment. However, there is an increased occurrence of CRC morbidity and mortality in low- and middle-income countries. Colorectal cancer is becoming an emerging public health concern in Ethiopia. We noticed that the incidence rates have been lower compared to more developed countries, but recent years have seen a noticeable increase. This rise is attributed to factors such as changes in diet, lifestyle, and an aging population. Common risk factors include dietary shifts towards processed foods and red meat, physical inactivity, obesity, smoking, and alcohol consumption. Unfortunately, in Ethiopia, screening programs for CRC are not widespread, and limited access to diagnostic facilities, lack of public awareness, and insufficient healthcare infrastructure contribute to late-stage diagnoses or left without diagnosis. Treatment options, including surgery, chemotherapy, and radiotherapy, are available but not uniformly accessible across the country, posing challenges for timely and effective treatment. Addressing colorectal cancer in Ethiopia requires a comprehensive approach to enhance public awareness, improve screening and early detection, expand treatment facilities, and train healthcare professionals to provide effective care.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 19-26"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical role of NLRP3 in drug resistance of cancers: Focus on the molecular mechanisms and possible therapeutics","authors":"Beena Briget Kuriakose ,&nbsp;Ahmed Hussein Zwamel ,&nbsp;Ayad Abdulrazzaq Mutar ,&nbsp;Subasini Uthirapathy ,&nbsp;Ashok Kumar Bishoyi ,&nbsp;K. Satyam Naidu ,&nbsp;Ahmed Hjazi ,&nbsp;Prashant Nakash ,&nbsp;Renu Arya ,&nbsp;Sami G. Almalki","doi":"10.1016/j.seminoncol.2025.152337","DOIUrl":"10.1016/j.seminoncol.2025.152337","url":null,"abstract":"<div><div>Nod-like receptor protein 3 (NLRP3) is a member of the leucine-rich repeat-containing protein (NLR) canonical inflammasome family. It regulates the pathophysiology of cancer by facilitating immune responses and apoptotic proteins. Furthermore, it has been observed that chemotherapy activates NLRP3 in human malignancies. The secretion of IL-1β and IL-22 to promote cancer spread may be triggered by NLRP3 activation. Furthermore, earlier studies have exhibited that NLRP3 may cause medication resistance when used in cancer treatments given that cell viability may be regulated by NLRP3 depletion. Additionally, clinical studies have demonstrated correlation between NLRP3 expression, lymphogenesis, and cancer metastasis. Various NLRP3 agonists may cause the EMT process, stimulate IL-1β and Wnt/β-catenin signaling, and alter miRNA function in drug-resistant cells. This review seeks to clarify the possibility involvement of NLRP3-related pathways in the control of cancer cells' resistance to widely used treatment approaches, such as chemotherapy. In the end, an improved perception of the corresponding mechanisms behind NLRP3′s tumor-supporting activities will help NLRP3-based treatments advance in the future.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 27-40"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender-Based Differences in the Efficacy of Anti-EGFR/BRAF/MEK Targeted Therapy in Patients with BRAF-Mutated Metastatic Colorectal Cancer","authors":"Laura Pala MD ,&nbsp;Tommaso De Pas MD ,&nbsp;Emilia Cocorocchio MD ,&nbsp;Chiara Catania MD ,&nbsp;Giovanni Ceresoli MD ,&nbsp;Daniele Laszlo MD ,&nbsp;Emma Zattarin MD ,&nbsp;Giovanna Rossi MD ,&nbsp;Fabio Conforti MD","doi":"10.1053/j.seminoncol.2024.10.004","DOIUrl":"10.1053/j.seminoncol.2024.10.004","url":null,"abstract":"<div><h3>Objectives</h3><div>We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed data from a cohort of patients with advanced colorectal-cancer (CRC) harboring BRAF V600E mutations, treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).A multivariable Cox proportional hazard regression model was used to assess the association between gender and PFS and OS, adjusted for other relevant clinical, pathological and molecular prognostic factors, including ECOG PS (0 vs 1-2), primary tumor site (right-side vs left-side), microsatellite instability status (instable [MSI] vs stable [MSS]), number of metastatic sites at treatment start, treatment type (double targeted therapy [ie, anti-EGFR + anti-BRAF] vs triple targeted therapy [ie, anti-EGFR + anti-BRAF + anti-MEK]) and mutational status of the RNF43 gene (wild type vs mutated).</div></div><div><h3>Results</h3><div>Ninety-eight patients with advanced CRC were included in the analysis: 59 (60%) were women and 39 (40%) men. The ORR was 43.1% in women vs only 23.7% in men (<em>p</em>-value = .05). Multivariable analysis adjusted for relevant clinical, pathological, and molecular variables associated with patients’ prognosis, showed a significantly shorter PFS and OS in men as compared with women: the adjusted-HR was, respectively, 1.65 (95%CI,1.00-2.69; <em>p</em> = .04) for PFS and 1.83 (95%CI,1.08-3.08; <em>p</em>-value = .02) for OS.</div></div><div><h3>Conclusions</h3><div>We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC harboring BRAF mutations that warrant further investigation.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 10-13"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study","authors":"Carlo Ronsini ,&nbsp;Eleonora Braca ,&nbsp;Mario Fordellone ,&nbsp;Federica Zito Marino ,&nbsp;Stefania Napolitano ,&nbsp;Antonio Raffone ,&nbsp;Luigi Cobellis ,&nbsp;Pasquale De Franciscis","doi":"10.1053/j.seminoncol.2025.01.001","DOIUrl":"10.1053/j.seminoncol.2025.01.001","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the correlation between BMI and MSI probability.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included 89 endometrial cancer patients treated at the Gynaecologic oncology unit of the University of Campania “Luigi Vanvitelli” from August 2023 to October 2024, and stratified by BMI: normal weight (<em>n</em> = 26), overweight (<em>n</em> = 31), obese (<em>n</em> = 26), and severely obese (<em>n</em> = 6). Microsatellite instability (MSI) was determined through immunohistochemical assessment of mismatch repair (MMR) protein expression: MLH1, PMS2, MSH2, and MSH6. Tumors were considered MSI if at least one of the four MMR proteins showed loss of expression. Univariate and multivariate logistic regression models were constructed to evaluate the correlation between BMI and MSI</div></div><div><h3>Results</h3><div>89 patients were enrolled. Obese and severely obese groups showed significantly higher MSI rates (50 % each) compared to normoweight (12 %) and overweight (29 %) groups (<em>P</em> = .013). MLH1 and PMS2 loss of expression were significantly higher in obese and severely obese women (MLH1: <em>P</em> = .003; PMS2: <em>P</em> = .014). Univariate logistic regression showed a significant positive correlation between BMI and MSI (OR 1.02, 95 % CI 1.01–1.04, <em>P</em> = .007). In multivariate analysis, adjusting for grading, stage, histotype, and age, BMI maintained a significant positive correlation with MSI (OR 1.02, 95 % CI 1.01–1.04, <em>P</em> = .048).</div></div><div><h3>Conclusions</h3><div>This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 1-6"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}