Clinical & Translational Oncology最新文献

{"title":"LncRNA FEZF1-AS1 promotes the tumorigenesis and suppresses ferroptosis in non-small cell lung cancer through the TNF-α/NF-κB pathway.","authors":"WenRui Hou, DianMing Li, JingXin Wang, WeiQi Yin","doi":"10.1007/s12094-025-04071-0","DOIUrl":"https://doi.org/10.1007/s12094-025-04071-0","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this research was to examine the impact of FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) on ferroptosis regulation in non-small cell lung cancer (NSCLC) cells and to understand its molecular mechanism.</p><p><strong>Methods: </strong>The effects of FEZF1-AS1 silencing on NSCLC cell proliferation, invasion, migration, and apoptosis were evaluated through functional assays, utilizing the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, flow cytometry, and Transwell assays. The levels of cellular reactive oxygen species, malondialdehyde, glutathione, and Fe²⁺ were measured using commercial assay kits. Proteins related to ferroptosis and the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) axis were analyzed using Western blot. Finally, rescue experiments were carried out by treating the cells with TNF-α.</p><p><strong>Results: </strong>FEZF1-AS1 expression was significantly upregulated in NSCLC cells. Moreover, FEZF1-AS1 silencing suppressed proliferation, migration, and invasion, while enhancing ferroptosis sensitivity in NSCLC cell lines. This knockdown also inhibited the TNF-α/NF-κB pathway. TNF-α attenuated both pro-ferroptotic and anti-tumor effects of FEZF1-AS1 silencing in NSCLC cells. Mechanistically, knockdown of FEZF1-AS1 modulates ferroptosis and malignant behaviors in NSCLC cells through suppression of the TNF-α/NF-κB axis.</p><p><strong>Conclusion: </strong>Our study uncovers a previously unrecognized mechanistic axis in which FEZF1-AS1 promotes NSCLC progression through suppressing ferroptosis by activating the TNF-α/NF-κB axis.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276505","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":"Epidrugs in cancer: mechanisms, applications, and future direction.","authors":"Roshni Bibi, Lakshmi Varshetha, Rakshit Kamal Lahary, Jahnavi Namburi, Fardeen Ahmed Laskar, Koustav Sarkar","doi":"10.1007/s12094-025-04064-z","DOIUrl":"https://doi.org/10.1007/s12094-025-04064-z","url":null,"abstract":"<p><p>DNA methylation, histone modifications, and regulation of non-coding RNA are all epigenetic modifications affecting cancer cells of origin and progression. These changes lead to changed expression of genes, which in turn is the reason for cancer occurrence in the form of inhibition of tumor suppressor genes or activation of oncogenes. Epigenetic changes, as opposed to genetic mutations, are reversible; thus, they seem to be interesting targets for therapeutic interventions. Current review summarizes the various types of epidrugs -DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors (HMTis), and BET inhibitors-are studied in this review. And the mechanisms of action, therapeutic potential, and clinical applications of epidrugs in several types of cancer, such as solid tumors (breast, lung, colorectal, and brain tumors) and hematological malignancies (acute myeloid leukemia (AML) and multiple myeloma). In addition, we address the challenges faced by epigenetic therapies, such as drug toxicity, off-target effects, and drug resistance. One of the rapidly evolving areas of cancer treatment is bringing new cancer treatments, and the use of epidrugs with conventional treatments, immunotherapy, and targeted therapy is an area. Epidrugs, drugs that control epigenetic pathways, have become substances that could be beneficial in cancer treatment. They can repress normal gene expression, reverse drug resistance, and make tumors penetrable to treatments that are already in place. Following instructions by tumor-specific epigenome analysis, personalized epigenetic therapy has the prospect to tailor the treatment schedule and to enhance medical outcome. Overcoming limitations and forming combination strategies to promote efficacy with less toxicity would foster the epigenetic treatment approach for cancer.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253538","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":"Unmasking hidden trends: subsite-specific mortality patterns in colorectal and anal cancers in Spain, 1999-2023.","authors":"Lucía Cayuela, Victoria Achaval, Gema Flox-Benítez, Aurelio Cayuela","doi":"10.1007/s12094-025-04072-z","DOIUrl":"https://doi.org/10.1007/s12094-025-04072-z","url":null,"abstract":"<p><strong>Objective: </strong>To analyse long-term mortality trends in Spain (1999-2023) for four colorectal cancer (CRC) subsites-colon, rectosigmoid junction, rectum, and anus/anal canal-by sex, age, and birth cohort.</p><p><strong>Methods: </strong>This ecological time-trend study used national mortality data from the Spanish National Statistics Institute, classified by ICD-10 codes C18-C21. Age-standardised mortality rates were calculated using the 2013 European Standard Population. Joinpoint regression estimated annual percentage changes, and age-period-cohort models evaluated generational and temporal effects.</p><p><strong>Results: </strong>Colon cancer mortality showed sex-specific patterns: a biphasic trend in men (initial rise, followed by decline) and a steady decrease in women. Rectal cancer mortality declined consistently in women, with a recent downward trend in men after years of stability. Mortality from rectosigmoid junction cancer remained relatively unchanged in both sexes. Anal cancer mortality increased steadily in men and, after an early decline, rose significantly in women, narrowing the sex gap. Mortality increased with age across all subsites, with men showing higher rates overall-except for anal cancer, where younger women's rates matched or surpassed those of men. Cohort analysis revealed generational declines in colon and rectal cancer mortality, contrasting with rising anal cancer risks, likely linked to increased HPV exposure. Period effects indicated notable mortality reductions for colon and rectal cancers but rising trends for anal cancer.</p><p><strong>Conclusions: </strong>While mortality has declined for colon and rectal cancers, stagnation in rectosigmoid junction and rising anal cancer deaths-especially among women-underscore the need for subsite-specific prevention strategies, including HPV-targeted interventions.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245657","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":"Prognostic significance of liver-to-muscle FDG uptake ratio and ınflammatory biomarkers in small cell lung cancer.","authors":"Kadriye Başkurt, Semra Demirtaş Şenlik, Galip Can Uyar, Enes Yeşilbaş, Ömür Berna Çakmak Öksüzoğlu, Osman Sütcüoğlu","doi":"10.1007/s12094-025-04070-1","DOIUrl":"https://doi.org/10.1007/s12094-025-04070-1","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is an aggressive malignancy frequently complicated by systemic inflammation, cachexia, and metabolic dysfunction. While 18F-FDG PET/CT is routinely used for disease staging, its potential to reflect host metabolic status through tissue-specific uptake metrics remains underexplored. We investigated the prognostic significance of the liver-to-rectus femoris mean standardized uptake value ratio (LRF) alongside systemic inflammatory markers in patients with SCLC.</p><p><strong>Methods: </strong>This retrospective study included 155 newly diagnosed SCLC patients who underwent baseline 18F-FDG PET/CT prior to systemic therapy. Quantitative PET/CT metrics-particularly LRF SUVmean-were analyzed in relation to clinical characteristics, inflammatory indices (CRP-to-albumin ratio [CAR], neutrophil-to-lymphocyte ratio [NLR]), and survival outcomes. Kaplan-Meier and multivariate Cox regression analyses were used to assess progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>An elevated LRF ratio (≥ 3.18) was independently associated with shorter PFS (7.52 vs. 10.22 months; p = 0.047) and OS (7.85 vs. 9.40 months; p = 0.021) in extensive-stage SCLC. Similarly, patients with CAR ≥ 0.29 had significantly worse progression-free survival (7.10 vs. 11.50 months; p = 0.001) and overall survival (7.55 vs. 13.74 months; p = 0.008) compared to those with CAR < 0.29. LRF SUVmean positively correlated with CAR and negatively with serum albumin. In contrast, NLR was not significantly associated with survival outcomes.</p><p><strong>Conclusion: </strong>The LRF SUVmean ratio represents a novel, noninvasive PET/CT-derived biomarker that reflects host metabolic frailty and correlates with systemic inflammation. Integration of metabolic imaging parameters such as LRF with established laboratory markers may improve prognostic stratification in SCLC and guide supportive care strategies.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240190","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":"Targeting the NF-κB pathway represents a potential strategy to attenuate HGF-induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.","authors":"Demin Jiao, Yu Chen, Xiang Liu, Wei Xu, Xiali Tang, Jun Chen, Li Yan, Qingyong Chen","doi":"10.1007/s12094-025-04067-w","DOIUrl":"https://doi.org/10.1007/s12094-025-04067-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the role of hepatocyte growth factor (HGF) overexpression in mediating resistance to KRAS G12C inhibitors in lung adenocarcinoma and to explore potential combination therapies to attenuate this resistance.</p><p><strong>Methods: </strong>Lentiviral transfection was used to establish HGF-overexpressing lung adenocarcinoma cell lines harboring the KRAS G12C mutation (H23 and H358). Cells were treated with KRAS G12C inhibitors either as monotherapy or in combination with inhibitors targeting the NF-κB, MEK/ERK, or PI3K/AKT/mTOR pathways. Drug sensitivity was assessed using pharmacological assays, and underlying mechanisms were evaluated through Western blot analysis.</p><p><strong>Results: </strong>HGF-induced resistance to KRAS G12C inhibitors varied significantly between the two cell lines. H23 cells overexpressing HGF exhibited only mild resistance, which could be reversed using MEK, mTOR, NF-κB, or MET inhibitors. In contrast, H358 cells developed strong resistance following HGF overexpression. Inhibitors of the NF-κB pathway were especially effective in counteracting this resistance, likely by modulating crosstalk among multiple KRAS downstream signaling pathways.</p><p><strong>Conclusion: </strong>These results indicate that targeting the NF-κB pathway may represent a promising therapeutic strategy to attenuate HGF- induced resistance to KRAS G12C inhibitors in lung adenocarcinoma.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233911","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":"Global regulatory variability in small-molecule inhibitor approvals: Differences in timelines, dosing, and pediatric indications across FDA, EMA, and PMDA.","authors":"Antía Gómez-Fernández, Alba Rubio-San-Simón, Sae Ishimaru, Jen-Hao Wu, C Michel Zwaan, Alwin D R Huitema, Francisco Bautista","doi":"10.1007/s12094-025-04066-x","DOIUrl":"https://doi.org/10.1007/s12094-025-04066-x","url":null,"abstract":"<p><strong>Purpose: </strong>Small-molecule inhibitors have transformed oncology in recent years. This study compared regulatory approvals of these agents across the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), focusing on timelines, dosing recommendations, and pediatric labelling.</p><p><strong>Methods: </strong>A review of regulatory databases was conducted to identify small-molecule inhibitors approved for adult malignancies. Drug labels were compared to determine dosing concordance (Fully, Partially, or Non-Concordant), approval dates, and pediatric indications. Data extraction involved two independent reviewers.</p><p><strong>Results: </strong>Fifty-five inhibitors were approved by all three agencies. Adult dosing was Fully Concordant in 49 (89%), partially in 4 (7%), and Non-Concordant in 2 (4%). The median approval gap was 25 months (range: 1-88). FDA granted first approval for 85.5% of agents, followed by PMDA (12.7%) and EMA (1.8%). Among these 55 drugs, only 15 had pediatric indications (27%), 7 of them (46.7%) approved across all three regions. No complete divergence in pediatric dosing was observed, although minimum age thresholds varied.</p><p><strong>Discussion: </strong>Despite strong alignment in adult dosing, regulatory disparities in approval timelines and pediatric labelling persist, risking delays in therapy availability. More harmonized multinational trials and regulatory alignment could facilitate timely approvals while allowing for population-specific considerations in dosing and safety.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226334","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":"Diagnostic imaging modalities to detect regional nodal involvement in oral squamous cell carcinoma: a systematic review and meta-analysis.","authors":"Maria Garcia-Iruretagoyena, Alejandra Outeiriño-Fernández, Maria Sobrido-Prieto, Amaia Bilbao-González, Alicia González-Mourelle","doi":"10.1007/s12094-025-04059-w","DOIUrl":"https://doi.org/10.1007/s12094-025-04059-w","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the most effective diagnostic imaging modality including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET/CT), and ultrasound (US) for the identification of regional lymph node involvement in patients with oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>A search was performed to identify qualified studies using PubMed, Scopus, and Web of Science electronic databases from January 2013 to December 2023. The outcome assessed was the diagnostic performance of different imaging techniques in the detection of cervical lymph node metastasis in OSCC, with lymph node yield in neck dissection specimens as the gold standard for validation. Summary estimates for diagnostic performance were sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs). Differences in sensitivities, specificities, and DOR were tested using a bivariate random effects model.</p><p><strong>Results: </strong>Twelve observational studies including PET/CT, MRI, and CT alone or combined in OSCC patients were included in the meta-analysis. Data from a single study based on US were insufficient to assess the value of this imaging modality. The pooled estimates of sensitivity were 0.87 for PET/CT, 0.70 for MRI, and 0.66 for CT. The corresponding pooled specificities were 0.79, 0.79, and 0.81, respectively. The DOR was 24.85 for PET/CT, 8.60 for MRI, and 8.59 for CT.</p><p><strong>Conclusion: </strong>PET/CT may be recommended in clinical practice for detecting cervical metastatic disease in OSCC patients as this technique showed the most favorable diagnostic performance as compared with MRI and CT.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226268","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":"Personalized recurrence risk prediction in early-stage breast cancer through an integrative mathematical model based on MammaPrint®, radiotherapy, phenotype, and clinicopathological factors.","authors":"J Sánchez Mazón, A de Juan Ferré, J M López Vega, C López López","doi":"10.1007/s12094-025-04065-y","DOIUrl":"https://doi.org/10.1007/s12094-025-04065-y","url":null,"abstract":"<p><strong>Purpose: </strong>To build a mathematical model with predictive capacity for the risk of recurrence in patients with early-stage breast cancer, based on four variables: the result of the MammaPrint®(MMP) test, postoperative radiotherapy (RT), tumor phenotype, and clinicopathological criteria. To estimate overall survival functions stratified by the dose of radiotherapy received.</p><p><strong>Methods: </strong>A retrospective cohort of 156 patients with early-stage breast cancer was analyzed. Patients were classified according to their MammaPrint®genomic risk (ultralow, low, or high). Multivariate logistic regression using Firth's method was employed to evaluate the risk of recurrence, adjusting for biologically effective dose (BED), molecular subtype, their MammaPrint®classification and clinico-pathologic features. Receiver operating characteristic (ROC) analysis was used to assess model discrimination. The Kaplan-Meier method was used to estimate overall survival (OS) functions. To assess statistically significant differences in survival between patient groups, the log-rank test was applied.</p><p><strong>Results: </strong>The predictive model, incorporating BED, genomic risk, molecular phenotype, and clinico-pathological classification, showed good calibration and discrimination (AUC: 0.755). The evaluation of OS according to the different BED levels provides clearer results regarding the clinical benefit of radiotherapy. This study reports statistically significant differences when comparing the group without radiotherapy (BED = 0 Gy) to the low-dose group (BED < 60 Gy), with a p-value of 0.0475.</p><p><strong>Conclusion: </strong>The predictive model fitted using Firth's penalized logistic regression demonstrated an adequate discriminative ability (AUC = 0.755). MMP was the variable with the greatest weight, followed by RT. These variables allow for a more accurate prediction of recurrence risk than traditional clinicopathological factors, supporting their value in the personalization of treatment. This study reports statistically significant differences when comparing the group without radiotherapy (BED = 0 Gy) to the low-dose group (BED < 60 Gy), with a p-value of 0.0475.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214295","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":"Macrophage-derived dendritic cells enhance antitumor immunity in a mouse model of head and neck squamous cell carcinoma.","authors":"Chubo Xie, Fanqin Wei, Tianrun Liu, Xiaochen Li, Kaiting Chen, Weiping Wen, Wei Sun","doi":"10.1007/s12094-025-03889-y","DOIUrl":"10.1007/s12094-025-03889-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the therapeutic potential of bone marrow macrophages-derived dendritic cells (BMΦDCs) in enhancing antitumor immunity against head and neck squamous cell carcinoma (HNSCC), focusing on their effects in inhibiting tumor growth, reducing metastasis, and modulating the tumor microenvironment.</p><p><strong>Methods: </strong>BMΦDCs were generated by culturing bone marrow cells with macrophage colony-stimulating factor (M-CSF) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). MTCQ-1 tumor lysates were used for antigen loading. The phenotypic characteristics of BMΦDCs were analyzed using flow cytometry. In vivo antitumor efficacy was assessed in subcutaneous and lung metastasis models in immunocompetent C57BL/6 mice. Tumor growth was monitored, and tumor tissues were collected for histological analysis using hematoxylin and eosin (H&E), Masson's trichrome, and anti-CD8 staining.</p><p><strong>Results: </strong>BMΦDCs displayed higher maturation marker expression (CD40, CD86) compared to traditional BMDCs. In the subcutaneous tumor model, BMΦDCs significantly inhibited tumor growth and enhanced cytotoxic T lymphocyte (CTL) activity. In the lung metastasis model, BMΦDCs effectively reduced metastatic burden. Histological analysis revealed increased CD8⁺ T cell infiltration and reduced tumor fibrosis in BMΦDC-treated mice. No significant toxicity or organ damage was observed.</p><p><strong>Conclusions: </strong>BMΦDCs are a promising immunotherapeutic approach for HNSCC, demonstrating superior antitumor efficacy, enhanced immune responses, and excellent biosafety. These findings highlight the potential of BMΦDCs in advancing cancer immunotherapy.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3938-3948"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057409","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":"Dysfunctional mismatch repair in patients with early triple-negative breast cancer.","authors":"María Muñiz-Castrillo, Noel Blaya Boluda, Esmeralda García-Torralba, Paula Jiménez-Fonseca, Carmen González Del Rey, Milagros Balbín, Ginés Luengo-Gil, Francisco Ayala de la Peña, Emilio Esteban González, Alberto Carmona-Bayonas","doi":"10.1007/s12094-025-03933-x","DOIUrl":"10.1007/s12094-025-03933-x","url":null,"abstract":"<p><strong>Background: </strong>While mismatch repair (MMR) deficiency is well-characterized in several cancers, its role in triple-negative breast cancer (TNBC) remains unclear. We comprehensively assessed MMR in early-stage TNBC, examining its prevalence, clinical correlations, prognostic value, relationship with microsatellite instability (MSI), and patterns of intratumoral heterogeneity.</p><p><strong>Methods: </strong>Two early-stage TNBC cohorts were investigated for germline mutations using next-generation sequencing, protein expression by immunohistochemistry, and MSI status through molecular detection. Associations with clinicopathological characteristics and survival were examined. Results were validated using The Cancer Genome Atlas (TCGA) data.</p><p><strong>Results: </strong>Among 259 patients, MMR deficiency was observed in 8.2%, all showing PMS2 loss, while 2 germline PMS2 mutations (2.7%) were detected. At the somatic level, 35.8% showed heterogeneous MMR expression, more frequently in earlier stages (IA-IIA 41.4% vs. IIB-III 22.4%, p = 0.04) and smaller tumors (cT1-2 39.1% vs. cT3-4 18.5%, p = 0.01). MMR status showed no significant associations with other clinicopathological variables or survival. No MSI was detected in MMR-deficient cases. The 5-year recurrence rate was 16.0% (95% CI 10.0-24.0) for MMR-intact, 20.0% (95% CI 4.5-43.0) for MMR-deficient, and 17.9% (95% CI 9.8-28.1) for heterogeneous tumors (p = 0.75). Pathological complete response to neoadjuvant chemotherapy was similar across MMR status groups. These findings were consistent with analyses using TCGA data.</p><p><strong>Conclusion: </strong>MMR system shows a low rate of alterations in TNBC, with its deficiency being infrequent and not correlated with MSI. Although MMR system isolated evaluation may not be justified in early-stage TNBC due to its limited clinical impact, its inclusion in multigene panels should be further considered.</p>","PeriodicalId":50685,"journal":{"name":"Clinical & Translational Oncology","volume":" ","pages":"3924-3937"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038004","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}