Translational cancer research最新文献

{"title":"A nomogram integrating multidimensional lymph node indicators with clinicopathological factors predicts overall survival in non-metastatic gastric cancer patients after radical gastrectomy.","authors":"Longjiang Fu, Wenjie Zhu, Jipeng Liu, Jun Huang","doi":"10.21037/tcr-2026-1165","DOIUrl":"10.21037/tcr-2026-1165","url":null,"abstract":"<p><strong>Background: </strong>Non-metastatic gastric cancer patients undergoing radical gastrectomy still show substantial prognostic heterogeneity. The conventional American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, particularly N stage, may be affected by variations in examined lymph node (ELN), resulting in stage migration. We aimed to evaluate the efficacy of a multifactor model incorporating the log odds of positive lymph nodes (LODDS), ELN, and N stage in survival prediction for patients with non-metastatic gastric cancer undergoing radical gastrectomy, and to construct an accurate prognostic prediction model.</p><p><strong>Methods: </strong>Clinicopathological data of patients with non-metastatic gastric cancer who underwent radical gastrectomy between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors for overall survival (OS) were determined using univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox analysis. A nomogram was subsequently established according to these factors. The prognostic performance and clinical utility of the model were evaluated in the training, validation, and overall cohorts using the concordance index (C-index), receiver operating characteristic (ROC) curves, Akaike information criterion (AIC), calibration curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Patients were stratified into different risk groups based on the total nomogram scores, and the discriminatory ability was validated using Kaplan-Meier survival curves.</p><p><strong>Results: </strong>Multivariate Cox analysis revealed that age, race, tumor size, T stage, N stage, ELN, LODDS, and chemotherapy status were independent prognostic factors. The areas under the curves (AUCs) of the nomogram for predicting 1-, 3-, and 5-year OS in the training, validation, and overall cohorts all exceeded 0.76, outperforming the AJCC TNM staging system (all AUCs <0.72). Calibration curves demonstrated close agreement between predicted and observed survival outcomes. DCA, NRI, and IDI analyses further confirmed that the nomogram provided superior clinical net benefit and improved discrimination compared with the TNM staging system. The risk stratification (low-, middle-, and high-risk groups) based on the model scores significantly distinguished different survival outcomes (P<0.001).</p><p><strong>Conclusions: </strong>The nomogram integrating multidimensional factors including LODDS, ELN, and traditional TNM staging is a reliable prognostic tool for patients with non-metastatic gastric cancer after radical gastrectomy. Compared with the conventional TNM staging system, this model exhibits superior predictive accuracy and clinical applicability, assisting clinicians in individualized prognostic assessment and adjuvant treat","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"648"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930961","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":"Predictive value of baseline risk factors and early prostate-specific antigen (PSA) kinetics for achieving deep PSA decline in metastatic hormone-sensitive prostate cancer: implications for treatment intensification.","authors":"Peimin Zhou, Zichuan Han, Yichuan Wang, Rui Yang, Wei Yu","doi":"10.21037/tcr-2026-1132","DOIUrl":"10.21037/tcr-2026-1132","url":null,"abstract":"<p><strong>Background: </strong>Early identification of treatment response is essential for risk-adapted management in metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to explore the predictive value of baseline clinicopathological factors and prostate-specific antigen (PSA) kinetics for deep PSA decline at 6 months in patients with mHSPC.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted involving 364 patients with de novo mHSPC. The primary endpoint was defined as PSA at 6 months ≤0.2 ng/mL. Logistic regression analyses were performed to identify independent predictors, and a nomogram was constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration analysis.</p><p><strong>Results: </strong>Independent predictors of poor PSA response included baseline alkaline phosphatase (ALP) >100 IU/L [odds ratio (OR) =0.363, P=0.02], International Society of Urological Pathology (ISUP) grade group 5 (OR =0.215, P=0.01), perineural invasion (OR =0.345, P=0.006), high disease volume (OR =0.270, P=0.02), and PSA >0.7 ng/mL at 2 months (OR =0.027, P<0.001). A predictive nomogram demonstrated discrimination (AUC = 0.907) and calibration. In a subgroup analysis of patients with PSA >0.7 ng/mL at 2 months, docetaxel addition was associated with a higher likelihood of achieving PSA response (OR =7.810, P=0.01).</p><p><strong>Conclusions: </strong>PSA at 2 months may serve as a useful biomarker for predicting deep PSA response in patients with mHSPC. The proposed nomogram may facilitate early risk stratification and warrants further validation in prospective multicenter studies.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"624"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931012","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":"Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.","authors":"Feng Zhang, Jian Fu, Xuxu Cui, Xutong Gao, Yanxia Kang","doi":"10.21037/tcr-2026-0696","DOIUrl":"10.21037/tcr-2026-0696","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains a leading cause of cancer incidence and mortality globally. Metabolic reprogramming promotes tumor progression and shapes an immunosuppressive tumor microenvironment. Galactose metabolism is involved in multiple malignancies, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop and internally validate a galactose metabolism-related multigene prognostic model for LUAD.</p><p><strong>Methods: </strong>A retrospective prognostic model development and internal validation study was performed using RNA sequencing (RNA-seq) and clinical data from 585 LUAD patients in The Cancer Genome Atlas (TCGA). Differential expression, functional enrichment, univariate and multivariate Cox regression were applied to construct a prognostic gene signature. Internal validation was performed using bootstrap resampling. Model performance was evaluated by time-dependent receiver operating characteristic (ROC), C-index, calibration, and Kaplan-Meier analysis. Associations between the model and immune infiltration, immunotherapy responsiveness, and tumor stemness were also analyzed.</p><p><strong>Results: </strong>A six-gene prognostic model (<i>GALT, GANC, PGM1, GALM, B4GALT1, PGM2</i>) was developed. The model showed good discrimination with 1-, 3-, and 5-year area under the curve (AUC) values of 0.719, 0.693, and 0.684, respectively. The low-risk group exhibited significantly longer survival, increased antitumor immune infiltration (CD8+ T cells, M1 macrophages, activated CD4+ memory T cells), higher expression of T cell proliferation-related genes, lower immune checkpoint expression, better predicted immunotherapy response, and lower tumor stemness compared with the high-risk group.</p><p><strong>Conclusions: </strong>We developed and internally validated a six-gene prognostic model for LUAD based on galactose metabolism. The model shows moderate prognostic performance and is associated with antitumor immunity and tumor stemness. It may be used for prognostic risk stratification and to guide personalized immunotherapy in LUAD.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"586"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931014","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":"Association between the systemic immune-inflammation index and overall survival in patients with leukemia: a multicenter cohort study.","authors":"Yiyang Chen, Muchen Ren, Sihui Liu, Tianyi Wang, Heyang Zhang, Junju He, Hanping Shi","doi":"10.21037/tcr-2026-1196","DOIUrl":"10.21037/tcr-2026-1196","url":null,"abstract":"<p><strong>Background: </strong>The systemic immune-inflammation index (SII; platelet × neutrophil/lymphocyte) is a well-established prognostic marker in solid tumors, but its clinical significance in leukemia remains unclear, where peripheral blood cytopenias may primarily reflect bone marrow failure rather than conventional cancer-related inflammation. This study aimed to evaluate the association between pretreatment SII and overall survival (OS) in patients with leukemia and to assess its prognostic relevance in a multicenter cohort.</p><p><strong>Methods: </strong>We retrospectively analyzed 609 leukemia patients from a multicenter registry, split into training (n=427) and validation (n=182) cohorts. Baseline SII was calculated before therapy. A data-derived SII threshold was identified in the training cohort using maximally selected rank statistics. OS was assessed using Kaplan-Meier curves, Cox regression, and restricted cubic splines (RCS). A nomogram was constructed based on the multivariable Cox model and internally evaluated using bootstrap calibration for 1- and 3-year survival.</p><p><strong>Results: </strong>An SII cutoff of 173.56 significantly separated survival (log-rank P<0.001). After adjustment for the demographic, comorbidity, and treatment variables available in the registry, higher SII (≥173.56) remained associated with a lower hazard of death [hazard ratio (HR) =0.41; 95% confidence interval (CI): 0.31-0.55; P<0.001]. Spline analyses suggested a nonlinear inverse association between SII and mortality. The nomogram showed acceptable internal calibration in both cohorts.</p><p><strong>Conclusions: </strong>Higher baseline SII was consistently associated with better OS in this multicenter leukemia cohort. This association may reflect differences in underlying disease burden and preserved hematopoietic function, rather than an independent biological effect of SII. Because leukemia subtype, disease status, and cytogenetic and molecular risk were unavailable, whether SII adds prognostic value beyond established leukemia risk factors remains uncertain. These findings support further evaluation of SII in well-characterized, subtype-specific cohorts.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"594"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931073","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":"Context-dependent roles of HtrA2/Omi in ovarian cancer: mitochondrial apoptotic function linking platinum sensitivity and acquired chemoresistance-a narrative review.","authors":"Yao Wu, Yu Gu, Xuemei Wang, Hongjing Cheng","doi":"10.21037/tcr-2026-1129","DOIUrl":"10.21037/tcr-2026-1129","url":null,"abstract":"<p><strong>Background and objective: </strong>Epithelial ovarian cancer often responds to platinum therapy but frequently relapses with acquired chemoresistance. HtrA2/Omi is a mitochondrial serine protease that can promote apoptosis after cytosolic release. This narrative review synthesizes ovarian-cancer-specific and mechanistic evidence and asks whether HtrA2/Omi is better understood as a static expression marker or as a stress-activated apoptotic effector linked to platinum response.</p><p><strong>Methods: </strong>PubMed, Web of Science, Scopus, and reference lists were searched through April 30, 2026 and updated through June 25, 2026 using terms related to HtrA2/Omi, PRSS25, ovarian cancer, platinum resistance, apoptosis, X-linked inhibitor of apoptosis protein (XIAP), mitochondrial release, cytosolic release and invasion. A structured narrative approach was used because the ovarian HtrA2/Omi literature is limited, heterogeneous, and unsuitable for pooled quantitative synthesis.</p><p><strong>Key content and findings: </strong>This review proposes a two-layer model. Baseline HtrA2/Omi abundance is context dependent and varies with histotype, assay platform, treatment state, and compartment resolution. In contrast, under platinum or mitochondrial stress, cytosolic HtrA2/Omi release more consistently supports XIAP relief, caspase activation, apoptosis, and platinum sensitivity. Persistent post-treatment HtrA2/Omi loss may mark an apoptosis-deficient resistant state.</p><p><strong>Conclusions: </strong>HtrA2/Omi should not be framed as a simple oncogene or tumor suppressor in ovarian cancer. Its clearest value is as a candidate response-linked, compartment-aware marker of platinum-induced apoptotic competence. Clinical use requires longitudinal, histotype-stratified and microenvironment-aware validation before treatment selection.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"654"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930865","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":"The risk factors and patterns for distant metastasis in early-stage cervical adenocarcinoma patients receiving radical surgery and adjuvant radiotherapy: the ATTRACT study.","authors":"Jia-Wei Zhu, Xi-Lin Yang, Yun-Can Zhou, Yan You, Peng Peng, Hong-Nan Zhen, Xi Wang, Xin Lian, Jun-Fang Yan, Fu-Quan Zhang","doi":"10.21037/tcr-2026-1079","DOIUrl":"10.21037/tcr-2026-1079","url":null,"abstract":"<p><strong>Background: </strong>Cervical adenocarcinoma (ADC) accounts for 15-25% of cervical cancer cases and carries a higher risk of distant metastasis (DM) and a poorer prognosis than squamous cell carcinoma (SCC). However, the DM patterns and risk factors in ADC patients receiving radical surgery and postoperative radiotherapy (PORT) remain insufficiently characterized. This study aimed to explore the DM pattern and risk factors associated with DM in ADC patients receiving radical surgery and postoperative radiotherapy.</p><p><strong>Methods: </strong>Patients with pathologically confirmed ADC after radical surgery were selected. The DM pattern was described using a metastatic organ distribution map. Survival outcomes were estimated using the Kaplan-Meier method, and intergroup differences were compared using the log-rank test. Risk factors for DM were identified through Cox regression analysis. A restricted cubic spline (RCS) curve was used to evaluate the association between the odds ratio (OR) for DM and cumulative platinum dose throughout treatment.</p><p><strong>Results: </strong>The most prevalent DM organ was the lung (51.1%), followed by liver (26.7%) and bone (24.4%). No significant difference regarding 5-year overall survival (OS) was observed between patients with single-site DM and those with multiple-site DM (44.2% <i>vs</i>. 44.9%; P>0.99). Similarly, patients without synchronous loco-regional failure (LRR) did not outperform those with synchronous LRR (49.6% <i>vs</i>. 44.4%; P=0.21). Lymph node metastasis (LNM) and depth of myometrial invasion (DOI) ≥1/2 were independent risk factors for DM. Three risk subgroups with distinct 5-year distant metastasis-free survival (DMFS) were constructed, including high-risk (LNM+ and DOI ≥1/2), middle-risk (LNM+ and DOI <1/2; LNM- and DOI ≥1/2), and low-risk subgroup (LNM- and DOI <1/2). Furthermore, cumulative platinum doses of 50 to 150 mg/m² were associated with a lower OR for DM, though this association did not reach statistical significance (P=0.02).</p><p><strong>Conclusions: </strong>The most common DM site for ADC patients after surgery and adjuvant radiotherapy was the lung. The risk factors for DM in those patients were LNM and DOI ≥1/2. Additionally, the prevention of DM could not be simply achieved by increasing the platinum dose during the primary treatment period.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"582"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930932","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":"Long-term safety and efficacy of BCMA-directed CAR T-cell therapies in multiple myeloma: comparative insights from Cilta-cel, Ide-cel, Anito-cel, and FCARH143.","authors":"Bryanna Reinhardt, Phyu Thin Naing, Muhamed Baljevic","doi":"10.21037/tcr-2026-0438","DOIUrl":"10.21037/tcr-2026-0438","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"663"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931098","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":"RECQL correlates with immune infiltration and serves as a prognostic biomarker and therapeutic predictor in gastric cancer.","authors":"Tana Lin, Lu Wang, Xin Wang, Haiqing Hu, Ying Li","doi":"10.21037/tcr-2026-0411","DOIUrl":"10.21037/tcr-2026-0411","url":null,"abstract":"<p><strong>Background: </strong>RecQ-like helicase (RECQL), a member of the RecQ-like DNA helicase family, plays a crucial role in maintaining genomic stability. However, its relevance in gastric cancer (GC) has not been fully investigated. This study aimed to explore the clinical significance, biological functions, and potential role of RECQL in the tumor immune microenvironment of GC through comprehensive bioinformatics analyses and <i>in vitro</i> experiments.</p><p><strong>Methods: </strong>Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) regression were performed using public datasets [The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE150290] to identify key genes associated with GC progression. Subsequently, key pathways were identified through functional enrichment analysis, while immune infiltration and spatial transcriptomic analyses were conducted to characterize RECQL expression and its association with the tumor immune microenvironment. Finally, the effects of RECQL knockdown on the biological function of GC cells were assessed through Cell Counting Kit-8 (CCK-8), colony formation, scratch, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays.</p><p><strong>Results: </strong>RECQL was significantly upregulated in GC tissues and correlated with advanced clinical stage and poor prognosis. Gene set enrichment analysis (GSEA) revealed a strong association between high RECQL expression and DNA repair pathway. Immune infiltration analysis indicated significant enrichment of M2 macrophages in the high-RECQL group, along with upregulation of immune checkpoint molecules including PDCD1, CTLA4, and CD274. Spatial transcriptomics further demonstrated co-localization of RECQL with myeloid cell-enriched regions in tumor parenchymal areas. Furthermore, <i>in vitro</i> experimental results indicated that RECQL was highly expressed in GC cell lines, and its knockdown effectively inhibited the viability, proliferation, and migration capabilities of HGC-27 cells, while enhancing their apoptosis.</p><p><strong>Conclusions: </strong>RECQL serves as a promising biomarker and potential therapeutic target in GC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"614"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931111","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":"Genetic insights into lung squamous cell carcinoma: how <i>TP53</i> and <i>CSMD3</i> co-mutations shape prognosis and immune response.","authors":"Dongmei Han, Caihong Wu, Dan Wang, Yinan Dong, Hao Jin","doi":"10.21037/tcr-2026-1534","DOIUrl":"10.21037/tcr-2026-1534","url":null,"abstract":"<p><strong>Background: </strong>Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of lung cancer cases and is often associated with smoking and various environmental factors. The prognostic and immunologic implications of <i>TP53</i> and <i>CSMD3</i> co-mutations in LUSC remain poorly understood. This study aimed to investigate the role of <i>TP53</i>/<i>CSMD3</i> co-mutations in LUSC using comprehensive bioinformatics analyses.</p><p><strong>Methods: </strong>Data from 487 LUSC patients were obtained from The Cancer Genome Atlas (TCGA) database, with external validation performed using the combined cohort. Patients were stratified into <i>TP53</i>/<i>CSMD3</i> co-mutation, single-mutation, and wild-type (WT) groups. Prognostic analysis was conducted using Kaplan-Meier survival curves. Tumor mutational burden (TMB) was calculated, and immune cell infiltration was assessed using multiple algorithms. Differentially expressed genes (DEGs) between co-mutated and WT groups were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A nomogram incorporating mutation status, gender, age, and tumor stage (T stage) was developed for individualized prognostic prediction.</p><p><strong>Results: </strong>The <i>TP53</i>/<i>CSMD3</i> co-mutated group exhibited significantly better overall survival (OS) compared to single-mutation and WT groups. TMB scores were markedly higher in co-mutated patients, suggesting potential sensitivity to immune checkpoint inhibitors. Immune infiltration analysis revealed distinct profiles, including elevated CD8 T cells and reduced immunosuppressive components, in the co-mutation group. A total of 403 DEGs were identified between co-mutated and WT groups, with significant enrichment in immune-related pathways. Mechanistically, the co-mutation was associated with distinct downregulation of complement negative regulators (<i>CFH</i>/<i>CFI</i>), indicating complement hyperactivation independent of TMB. The constructed nomogram provided accurate individualized prognostic assessments.</p><p><strong>Conclusions: </strong>The co-mutation of <i>TP53</i> and <i>CSMD3</i> identifies a distinct <i>LUSC</i> subtype with favorable survival, marked by high TMB and an immune-activated microenvironment. Beyond TMB-driven neoantigen generation, the significant downregulation of complement negative regulators (<i>CFH</i>/<i>CFI</i>) reveals an independent complement hyperactivation pathway associated with <i>CSMD3</i> loss. The constructed nomogram provides accurate individualized survival prediction. These findings establish <i>TP53</i>/<i>CSMD3</i> co-mutation as a promising prognostic biomarker and offer mechanistic insights for personalized immunotherapy strategies. Future prospective cohorts are warranted to validate its predictive value.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"576"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931140","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":"SERPINE1-centric inflammatory signature associates with treatment resistance and survival in laryngeal squamous cell carcinoma.","authors":"Jin Peng, Weiquan Ding, Qingxuan Niu, Wuguo Deng, Fei Lin, Ankui Yang","doi":"10.21037/tcr-2026-1190","DOIUrl":"10.21037/tcr-2026-1190","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Laryngeal squamous cell carcinoma (LSCC) prognosis remains poor despite treatment advances. More accurate prognostic assessment models can help guide individualized treatment and improve prognosis. Chronic inflammation contributes to tumorigenesis, yet inflammatory response-related genes (IRGs) in LSCC prognosis are underexplored. This study aimed to construct an IRG prognostic signature for LSCC and further dissect core IRG-mediated mechanisms of immune escape and chemoresistance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptional profiles and clinical data from LSCC patients were retrieved from The Cancer Genome Atlas (TCGA). IRGs were sourced from Gene Set Enrichment Analysis (GSEA) hallmark gene set. We identified differentially expressed IRGs linked to survival outcomes in LSCC. Key IRGs were subsequently selected using least absolute shrinkage and selection operator (LASSO) Cox regression analysis to establish an inflammatory risk score model. This model underwent internal validation within the TCGA cohort and external validation using independent Gene Expression Omnibus (GEO) datasets. We further assessed the model's association with the tumor immune microenvironment and the impact of IRGs on chemotherapy response. Finally, the functional roles of interested signature IRG were experimentally validated in LSCC cell lines.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Four significant IRGs (&lt;i&gt;AQP9&lt;/i&gt;, &lt;i&gt;ITGA5&lt;/i&gt;, &lt;i&gt;LCK&lt;/i&gt;, &lt;i&gt;SERPINE1&lt;/i&gt;) were identified to build the risk score model. The model stratified LSCC patients into distinct prognostic groups: TCGA cohort: 5-year area under the curve (AUC) =0.836, P&lt;0.001; GSE25727 cohort: 5-year AUC =0.706, P=0.02; GSE27020 cohort: 5-year AUC =0.798, P&lt;0.01. Multivariate analysis confirmed the risk score as an independent prognostic factor (P&lt;0.05). High-risk patients showed reduced immune cell infiltration (CD8+ T cells, dendritic cells) and suppressed immune pathways. Multi-algorithm immune analysis further revealed defective antigen presentation and reduced anti-tumor immune infiltration in high-risk LSCC, promoting tumor immune escape. GSEA/Gene Ontology (GO) enrichment combined with drug sensitivity prediction further revealed that high-risk tumors activate invasive signaling and acquire broad chemoresistance alongside impaired anti-tumor immunity. SERPINE1 might be associated with chemotherapy resistance and exhibited the highest alteration frequency (predominantly amplification) and overexpression in LSCC tissues. Its knockdown significantly suppressed proliferation, migration, invasion and chemoresistance in LSCC cells. Immunohistochemistry (IHC) confirmed tumor SERPINE1 overexpression (P=0.002 vs. normal tissues), correlating with poor survival (P&lt;0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The 4-IRG risk signature is a reliable prognostic indicator reflecting immune dysfunction in LSCC. SERPINE1 is validated as a therapeutic target and biomarker, enriching our underst","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"584"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931158","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}