Oncology Letters最新文献

{"title":"Breaking senescence restriction: MAFK-AREG axis promotes NSCLC cells to resist doxorubicin.","authors":"Ningning Fan, Guanying Liang, Jiayue Shao, Qi Wang, Lu Fu","doi":"10.3892/ol.2026.15646","DOIUrl":"10.3892/ol.2026.15646","url":null,"abstract":"<p><p>Musculoaponeurotic fibrosarcoma oncogene homolog K (MAFK) and amphiregulin (AREG) promote non-small cell lung cancer (NSCLC) progression. However, whether MAFK regulates AREG to mediate the escape of NSCLC cells from doxorubicin (DOX)-induced senescence remains unclear. In the present study, chemotherapy-modulated senescence-related genes were identified through bioinformatics analysis. Human non-small cell lung adenocarcinoma cell lines (A549 and PC-9 cells) were treated with DOX to generate persistent A549 cells (PACs) and persistent PC-9 cells (PPCs). The expression levels of MAFK, AREG and the senescence-associated protein p21 wild-type p53-activated fragment 1 (p21waf1) were evaluated using western blotting and reverse transcription-quantitative PCR. Senescence-associated β-galactosidase staining and colony formation assays were performed to assess cellular senescence and proliferation. The proportions of senescent and proliferating PACs and PPCs were quantified using flow cytometry. A chromatin-immunoprecipitation assay was performed to examine the regulatory association between MAFK and AREG. AREG was associated with cellular senescence, as demonstrated by changes in senescence markers. In A549 and PC-9 cells, DOX treatment upregulated p21waf1 expression, induced senescence, inhibited proliferation and downregulated both MAFK and AREG expression. By contrast, PACs/PPCs exhibited enhanced proliferation alongside elevated MAFK and AREG levels. PACs and PPCs comprised 60-70% senescent cells and 30-40% proliferating cells. MAFK bound directly to the AREG promoter region. In addition, MAFK overexpression reversed the suppressive effect of AREG knockdown on the proliferation of A549 and PC-9 cells. Collectively, MAFK enabled NSCLC cells to escape DOX-induced senescence by upregulating AREG and facilitated cell proliferation upon DOX treatment.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"291"},"PeriodicalIF":2.1,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel prognostic biomarker combining <i>TP53</i> loss-of-function and amplification of different combinations of nine genes in lung squamous cell carcinoma treated with chemotherapy.","authors":"Yuli Li, Ting Hou, Hongjie Liu, Haiwei Du, Li Qiu, Yajing Zhang, Guiping Zhang, Yuan Tang","doi":"10.3892/ol.2026.15644","DOIUrl":"10.3892/ol.2026.15644","url":null,"abstract":"<p><p>Lung squamous cell carcinoma (LUSC) is a prevalent subtype of lung cancer, which is primarily characterized by poor prognosis due to the lack of targeted therapies, while a large proportion of patients show limited response to chemotherapy. The present study aimed to identify predictive chemotherapy biomarkers based on genomic alterations in LUSC. Non-negative matrix factorization clustering was applied to classify patients with LUSC into distinct subgroups based on genomic alterations. Subsequently, chemotherapy efficacy was predicted via exploring gene signatures, and the results were validated using The Cancer Genome Atlas database (TCGA). A total of four distinct clusters were classified. Cluster 1 and <i>TP53</i> loss-of-function (<i>TP53</i> LOF) variations were each independently associated with poor prognosis, irrespective of clinical stage. Based on the molecular characteristics of the initial clusters, the classification was further refined by further incorporating <i>TP53</i> LOF and gene amplification (amp). Patients without <i>TP53</i> LOF, who harbored amplification of at least one of nine specified genes [<i>PIK3 catalytic subunit, cyclin D1, fibroblast growth factor (FGF) 19, FGF3, FGF4, FGF receptor 1, kinase insert domain receptor, KIT proto-oncogene</i> and <i>platelet derived growth factor receptor α</i>] displayed the longest progression-free survival (PFS). By contrast, patients with <i>TP53</i> LOF but lacking amplification of at least one of nine genes [Amp(9G)] exhibited the worst overall survival compared with the other subgroups. Validation in the TCGA database confirmed the prognostic significance of this classification, with Amp(9G) without <i>TP53</i> LOF predicting the most favorable PFS, and <i>TP53</i> LOF without Amp(9G) indicating the least favorable PFS. Therefore, a composite biomarker integrating Amp(9G) and <i>TP53</i> LOF was identified as a prognostic indicator for patients with LUSC treated with first-line chemotherapy. Overall, the results of the present study suggest that the absence of <i>TP53</i> LOF combined with the presence of Amp(9G) could be associated with improved response to first-line chemotherapy in LUSC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"289"},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of efficacy comparisons between standard- and low-dose Bacillus Calmette-Guerin vaccines in managing non-muscular invasive bladder cancer.","authors":"Xiaoxi Liu, Yige Bao","doi":"10.3892/ol.2026.15643","DOIUrl":"10.3892/ol.2026.15643","url":null,"abstract":"<p><p>Intravesical Bacillus Calmette-Guerin (BCG) is the first-line therapy for non-muscle-invasive bladder cancer (NMIBC), yet its clinical use is limited by high adverse event rates and a global supply shortage. A comparison was conducted to explore the effectiveness of low- vs. standard-dose BCG vaccines in patients diagnosed with NMIBC). The search queries utilized for China National Knowledge Infrastructure and Wanfang databases included the key words 'dose', 'BCG vaccine' and 'bladder cancer/bladder tumour'. Embase, PubMed and Web of Science databases were searched using the key words 'dose', 'Bacillus Calmette-Guerin vaccine' and 'urinary bladder neoplasm' to identify randomized controlled trials published up to December 2024. The relevant data were collected from the included study articles and a meta-analysis was conducted utilizing the Review Manager 5.4 software to evaluate the therapeutic effects of low- and standard-dose BCG vaccines. In total, 13 studies were included in the present meta-analysis after literature search, selection process and quality assessment. The present meta-analysis findings suggested that the recurrence rate in patients receiving low-dose therapy was notably higher compared with that in patients receiving standard-dose therapy [odds ratio (OR)=1.38; 95% CI, 1.10-1.73; P=0.006]. However, the incidence of adverse events was lower compared with that in the standard-dose treatment group (OR=0.39; 95% CI, 0.29-0.52; P<0.00001) and no marked differences in tumour progression, tumour-specific or overall mortalities were detected between the two groups (all P>0.05). The funnel plot revealed no notable publication bias. In conclusion, the present meta-analysis confirmed the effectiveness of low-dose BCG treatment for patients with NMIBC and highlighted its potentially notable advantage in managing adverse events in patients with NMIBC in the future.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"288"},"PeriodicalIF":2.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative evidence for associations between matrix metalloproteinase-1, -3 and -8 variants and cancer risk.","authors":"Suqin Xu, Xianping Liu, Chenglu Huang","doi":"10.3892/ol.2026.15640","DOIUrl":"10.3892/ol.2026.15640","url":null,"abstract":"<p><p>Matrix metalloproteinase (MMP) gene polymorphisms have been implicated in cancer susceptibility; however, the results from previous studies have been inconsistent across populations and tumor types. The present study aimed to systematically evaluate the associations between MMP-1, MMP-3 and MMP-8 polymorphisms and cancer risk through a comprehensive meta-analysis. A total of 36,368 cancer cases and 40,246 controls from eligible studies were included. Pooled odds ratios and 95% confidence intervals were calculated to assess the associations between selected MMP polymorphisms and cancer risk. Venice criteria and false-positive report probability were applied to evaluate the cumulative evidence. Subgroup analyses according to ethnicity, genetic model and cancer type were conducted. Functional annotation was also integrated to explore potential biological mechanisms. In total, three polymorphisms (MMP-3 rs35068180, MMP-3 rs3025058 and MMP-1 rs1799750) were found to be significantly associated with the risk of seven types of cancer. Of these, strong evidence was assigned to two single nucleotide polymorphisms for three cancer risks (four associations), including MMP-3 rs3025058 with esophageal cancer in all populations under the dominant model, MMP-1 rs1799750 with glioblastoma in all populations under the recessive model and MMP-1 rs1799750 with renal cancer in all populations under both the recessive and allelic models. A total of six associations showed moderate evidence, while 14 were classified as weak. Notably, the effect sizes and statistical significance varied by ethnicity, genetic model and cancer type, suggesting context-dependent and population-specific effects. Functional annotation indicated that key variants may affect gene expression and tumor biology via regulation of promoter or enhancer activity. No significant association was observed between MMP-8 polymorphisms and cancer risk. The findings provide new insights into the complexity of gene-environment interactions underlying cancer susceptibility. This comprehensive meta-analysis highlights the complex, context-dependent associations of MMP-1, MMP-3 and MMP-8 polymorphisms with cancer risk. The results of the present study underscore the need for large, multi-ethnic studies and integrated genomic, functional and environmental analyses to clarify the roles of MMP variants in cancer development and to identify high-risk populations for precision prevention.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"286"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 inhibitors combined with tyrosine kinase inhibitor-associated hypothyroidism is a predictive factor for antitumor effectiveness in male patients with hepatocellular carcinoma.","authors":"Bailu Cao, Min Ai, Ping Huang, Huan Zhong","doi":"10.3892/ol.2026.15641","DOIUrl":"10.3892/ol.2026.15641","url":null,"abstract":"<p><p>Tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors are well-established first-line systemic therapies for hepatocellular carcinoma (HCC), with hypothyroidism as a prominent immune-related adverse event. However, the female sex is a known risk factor for thyroid dysfunction associated with TKIs. The present study aimed to determine whether PD-1 inhibitor plus TKIs-induced hypothyroidism predicts treatment efficacy in male patients with HCC. A retrospective cohort study enrolled 77 male patients with confirmed HCC who received PD-1 inhibitor-TKIs combination therapy at Nanjing Second Hospital (Nanjing, China). According to the evaluation of thyroid function, patients were divided into normal thyroid function and hypothyroidism groups, based on serial thyroid function evaluations. The primary endpoint of the present study was progression-free survival (PFS). Baseline serum thyroid-stimulating hormone (TSH) and thyroglobulin antibody (TgAb) levels were significantly higher in the hypothyroidism group compared with the group with normal thyroid function [TSH, 4.2 mIU/l; 95% confidence interval (CI), 2.0-4.6 mIU/l vs. 1.7 mIU/l (95% CI, 1.2-3.1 mIU/l); P<0.001; TgAb, 12.4 IU/ml (95% CI, 2.1-18.2 IU/ml) vs. 1.4 IU/ml (95% CI, 0.8-5.0 IU/ml); P=0.007]. The group with hypothyroidism had a median PFS of 8.0 months, which was longer compared with the group with normal thyroid function (6.1 months; P<0.001). Cox regression analysis demonstrated that PD-1 inhibitors plus TKIs-induced hypothyroidism [hazard ratio (HR)=0.320; 95% CI, 0.160-0.641; P=0.001] and baseline serum α-fetoprotein >200 ng/ml (HR=2.354; 95% CI, 1.277-4.340; P=0.008) were independent prognostic factors of PFS in male patients with HCC. In conclusion, <i>de novo</i> hypothyroidism during PD-1 inhibitors combined with TKIs is associated with prolonged PFS in male patients with HCC.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"285"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of ct-DNA and mutational status in liquid biopsy of patients with metastatic colorectal cancer.","authors":"George Zarkavelis, Melina Yerolatsite, Panagiotis Ntellas, Aikaterini Tsantikidi, Irene Papadopoulou, Nanteznta Torounidou, Katerina Dadouli, George Nasioulas, Eleftherios Kampletsas, George Pentheroudakis","doi":"10.3892/ol.2026.15637","DOIUrl":"10.3892/ol.2026.15637","url":null,"abstract":"<p><p>Liquid biopsy has become an increasingly important tool in clinical oncology due to the utility of circulating tumor DNA (ct-DNA). Plasma ct-DNA levels reflect the tumor burden of patients and provide valuable information for personalized treatment strategies. Colorectal cancer (CRC) is among the most frequently diagnosed malignancies worldwide and remains a leading cause of cancer-related mortality. The implementation of personalized therapy can notably improve clinical outcomes in these patients. The present study aimed to evaluate ct-DNA in patients with metastatic CRC undergoing therapy at the Department of Medical Oncology, University Hospital of Ioannina (Ioannina, Greece), using next-generation sequencing (NGS) to identify tumor mutations in both tissue and cell-free plasma DNA. A total of 45 patients newly diagnosed with metastatic CRC were enrolled in the current study. ct-DNA evaluation was performed at diagnosis, and both tissue and plasma samples were analyzed using NGS to assess the mutational profile. The most frequent mutation identified was in <i>KRAS</i>. A high level of concordance was observed between tissue and plasma samples regarding ct-DNA detection and mutational status. Sequential ct-DNA analysis during therapy revealed dynamic changes in mutation profiles over the course of treatment. In conclusion, liquid biopsy offers marked clinical value as a minimally invasive tool for personalized therapy in metastatic CRC. NGS-based liquid biopsy enables real-time evaluation of ct-DNA and mutation status during treatment, supporting therapeutic decision-making and disease monitoring.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"283"},"PeriodicalIF":2.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13177284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy retreatment with serplulimab vs. chemotherapy in extensive-stage advanced small cell lung cancer.","authors":"Xinhang Gu, Xue Wu, Jiaxiao Geng, Yan Wang, Chengxin Liu","doi":"10.3892/ol.2026.15638","DOIUrl":"10.3892/ol.2026.15638","url":null,"abstract":"<p><p>The present study compared the effectiveness and safety of immunotherapy retreatment with serplulimab vs. chemotherapy in extensive-stage small cell lung cancer (ES-SCLC). This real-world retrospective cohort study included patients with ES-SCLC who experienced failed first-line immunotherapy and received second-line immunotherapy retreatment (serplulimab) or chemotherapy. There were 67 and 93 patients in the serplulimab and chemotherapy groups, respectively. Progression-free survival (PFS) time was prolonged with the administration of serplulimab compared with chemotherapy [median, 7.65 vs. 5.25 months; hazard ratio (HR), 0.601; 95% confidence interval (CI), 0.426-0.848; P=0.003]; the results were similar after confounder adjustment in the multivariable Cox regression analysis (HR, 0.572; 95% CI, 0.395-0.828; P=0.003). The median overall survival (OS) time was 15.56 vs. 13.48 months (HR, 0.680; 95% CI, 0.478-0.966; P=0.031). Multivariable Cox regression analysis showed that serplulimab was also an independent protective factor for OS compared with chemotherapy (HR, 0.158; 95% CI, 0.096-0.261; P<0.001). The incidence of grade ≥3 adverse events was 29.9 and 34.4% with serplulimab and chemotherapy, respectively (P=0.760). In conclusion, immunotherapy retreatment with serplulimab is associated with prolonged PFS and OS times compared with chemotherapy in ES-SCLC, with a similar safety profile.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"282"},"PeriodicalIF":2.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13177285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing elucidates the distinct mutational landscape of SMARCA4-deficient lung cancer.","authors":"Feicheng Yang, Yuzhong Yang, Zhihong Chen, Yanchun Li, Yinghui Song","doi":"10.3892/ol.2026.15636","DOIUrl":"10.3892/ol.2026.15636","url":null,"abstract":"<p><p>Lung cancer with SMARCA4 deficiency has a high degree of malignancy and a low degree of differentiation. It is a newly discovered type of tumor closely related to gene mutations. The present study aimed to clarify the molecular mutation characteristics of <i>SMARCA4</i>-deficient lung cancer using next-generation sequencing (NGS). NGS sequencing was conducted to analyze the gene expression profile of 15 patients with <i>SMARCA4-</i>deficient lung cancer, with positive or negative EGFR expression, and the association between gene mutation sites and <i>SMARCA4</i> expression was analyzed. The pathological characteristics of <i>SMARCA4</i>-deficient lung cancer were analyzed using immunohistochemistry. The likelihood of positivity for the programmed cell death 1 ligand 1 protein was low, and there were no instances of positivity for anaplastic lymphoma kinase protein expression. Approximately 50% of Ki67-positive expression regions were present. The BOI-related E3 ubiquitin-protein ligase 1 protein encoded by the <i>SMARCA4</i> gene was not expressed; however, the INI1 protein encoded by <i>SMARCB1</i> was partially positive (6/15), which showed that the expression of INI1 was not affected by <i>SMARCA4</i>. The <i>SMARCA4</i> mutation types included c.2729C>T (p.T910M), c.3634_3636del (p.E1212del), c.3574C>T (p.R1192C), and c.3733G>A (p.A1245T). <i>NQO1</i> and <i>TP53</i> mutations were detected in nine patients, <i>XRCC1</i> mutation was detected in seven patients, <i>DPYD</i> mutation was detected in six patients and <i>TYMS</i> mutation was detected in five patients. The mutated genes were more resistant to the EGFR tyrosine kinase inhibitor. In conclusion, patients with <i>SMARCA4</i>-deficient lung cancer have distinct immunohistochemical characteristics, and <i>SMARCA4</i> has been implicated in the incidence and progression of tumors through different mutation mechanisms.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"281"},"PeriodicalIF":2.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational landscape in the precancerous stages of sporadic colorectal cancer.","authors":"Anna Valickova, Marketa Urbanova, Josef Horak, Jiri Jungwirth, Jan Kral, Tomas Hucl, Veronika Makajevova, Sandra Summerova, Pavel Kohout, Radoslav Matej, Pavel Vodicka, Veronika Vymetalkova","doi":"10.3892/ol.2026.15634","DOIUrl":"10.3892/ol.2026.15634","url":null,"abstract":"<p><p>Colorectal adenoma (CRA) is a precancerous lesion that can progress to colorectal carcinoma (CRC); however, its malignant potential varies considerably. The present study aimed to characterize the putatively pathogenic variants (PPVs) of CRA and to assess their potential clinical relevance in identifying lesions with an increased risk of progression at precancerous stages. PPVs in a panel of 176 cancer-associated genes were analyzed in 67 CRA samples and matched adjacent normal mucosa using next-generation sequencing. The panel included genes involved in DNA repair pathways, cell cycle regulation and the genes directly associated with CRC development. PPVs in CRA tissue were identified in 44 patients. The most frequently mutated genes were found to be <i>APC, KRAS, FBXW7, BRAF</i> and <i>MAP2K4</i>, with <i>APC</i> mutations being the most prevalent. A higher frequency of PPVs was observed in CRA with high-grade dysplasia and tubulo-villous features. Notably, among the entire sample set, there were 10 hyperplastic polyps, which are generally considered low risk; however, three carried PPVs, specifically one polyp carried <i>APC, MAP2K4</i> and <i>FEN1</i> mutations, another polyp carried <i>BRAF</i> and <i>POLQ</i> mutation, and a third carried a <i>MAP2K4</i> mutation. These findings suggested that mutational profiling may provide additional molecular information beyond histopathological assessment and could support improved risk stratification of colorectal lesions in early, precancerous stages. Such molecular characterization may be of value for identifying subsets of patients who could benefit from closer clinical surveillance.</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"279"},"PeriodicalIF":2.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the efficacy of immune checkpoint inhibitors with and without microwave ablation in advanced hepatocellular carcinoma in real-world clinical practice: A retrospective cohort study.","authors":"Chun Wei, Sizhong Chen, Li Ding, Ting Zhou, Fan Huang, Yong Wang, Ou Jiang, Yu Liu","doi":"10.3892/ol.2026.15633","DOIUrl":"10.3892/ol.2026.15633","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) are widely used in the treatment of hepatocellular carcinoma (HCC). Microwave ablation (MWA), a form of thermal ablation, may elicit systemic immune responses and could potentially augment the clinical activity of ICIs, particularly in advanced disease. The present study retrospectively assessed 52 eligible patients with limited progression or oligometastatic disease treated between January 2022 and January 2024 with either ICIs alone or ICIs plus MWA. A total of 21 patients received the combination regimen (predominantly programmed cell death protein 1 inhibitors), and 31 received ICI monotherapy. The recorded baseline characteristics did not suggest notable between-group imbalances; however, key tumor burden descriptors were incompletely captured, and residual confounding cannot be excluded. The objective response rate (ORR) and disease control rate (DCR) were 9.7 and 51.6% with ICIs alone, respectively, vs. 28.6 and 81.0% with ICIs plus MWA. The DCR was higher in the combination group (P=0.031), whereas the between-group difference in ORR was not statistically significant (P=0.133) compared with the monotherapy group. Median overall survival (OS) was 11.0 months with monotherapy and 16.8 months with combination therapy (log-rank P=0.008). In the multivariable Cox analysis, the combination therapy was associated with improved OS (adjusted HR=0.176; 95% CI, 0.048-0.642; Wald P=0.008); however, given the small sample size and limited number of OS events, this adjusted HR may be imprecise and sensitive to model specification and should be interpreted as exploratory. The median progression-free survival (PFS) was 4.0 vs. 9.0 months (log-rank P<0.001), consistent with the multivariable model (adjusted HR=0.270; 95% CI, 0.122-0.595; Wald P=0.001). There was not a clear unexpected safety pattern observed, but safety comparisons were descriptive only and underpowered. In the present retrospective cohort of selected patients with advanced HCC and limited progression/oligometastatic disease, ICIs plus MWA was associated with longer PFS and OS compared with ICIs alone. The interpretation is limited by the small sample size, potential residual confounding and model instability. The direction of benefit was consistent across Kaplan-Meier and Cox analyses, although the adjusted OS effect estimate may be imprecise. The present study was registered on ClinicalTrials.gov on 03 September 2024 (trial no. NCT06581497).</p>","PeriodicalId":19503,"journal":{"name":"Oncology Letters","volume":"32 1","pages":"278"},"PeriodicalIF":2.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}