Translational cancer research最新文献

{"title":"Overexpression of TCF7L2 promotes the viability and migration of MHCC-97H human hepatocellular carcinoma cells by upregulating MT-ND4L.","authors":"Rong Chen, Weijie Liu, Zilong Yang, Wei Hao, Ben Chen, Shuaixing Zhao, Longyi Zheng, Jin Lu","doi":"10.21037/tcr-2026-0562","DOIUrl":"10.21037/tcr-2026-0562","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive cancer with high metabolic adaptability. TCF7L2, a transcription factor implicated in type 2 diabetes and cancer, is overexpressed in HCC. However, its specific role in HCC metabolic reprogramming is not well defined. We aimed to elucidate the previously unrecognized molecular mechanisms through which TCF7L2 impacts HCC progression.</p><p><strong>Methods: </strong>To investigate the function of TCF7L2, a stable MHCC-97H cell line with TCF7L2 overexpression was established via lentiviral transduction. Cell viability and migration were assessed by Cell Counting Kit-8 (CCK-8) and Transwell assays. Transcriptomic profiling [RNA sequencing (RNA-seq)] was performed to identify differentially expressed genes (DEGs). Functional enrichment analysis [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA)] and bioinformatics promoter analysis (the JASPAR CORE database) were conducted. Clinical correlations, survival analysis, and tumor microenvironment (TME) interrogation were performed using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and single-cell datasets [Human Protein Atlas (HPA), CellChat]. Drug sensitivity was predicted via the Genomics of Drug Sensitivity in Cancer (GDSC) database.</p><p><strong>Results: </strong>TCF7L2 overexpression significantly promoted HCC cell proliferation and migration. Transcriptomic analysis revealed that TCF7L2 drives a profound metabolic shift, with key enrichments in lipid homeostasis, fatty acid β-oxidation, and the PI3K/Akt pathway. Mechanistically, TCF7L2 directly binds to the promoter of <i>CPT1A</i>, the rate-limiting enzyme of fatty acid oxidation, and indirectly upregulates the mitochondrial gene MT-ND4Lvia a strong positive correlation with the mitochondrial transcription factor <i>TFAM</i>. In clinical cohorts, TCF7L2 was overexpressed in HCC and its expression correlated positively with MT-ND4L, MKI67, and SNAI1, and served as a predictor of poor overall survival (OS). Furthermore, TCF7L2-high tumors were enriched in hepatic progenitor cell (HPC)-like niches, mediated by enhanced ANGPTL4 signaling. High TCF7L2 expression predicted increased sensitivity to PI3K/mTOR pathway inhibitors.</p><p><strong>Conclusions: </strong>TCF7L2 acts as a master metabolic regulator in HCC, coordinating lipid catabolism and mitochondrial biogenesis to drive aggressive tumor behavior. It further remodels the TME towards an HPC-like state and predicts sensitivity to metabolic-targeted therapies. These findings identify TCF7L2 as a key prognostic biomarker and a promising therapeutic target.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"575"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930990","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":"Residual disease in HER2-positive early breast cancer: are we escalating the RIGHT patients to T-DM1 or T-DXd?","authors":"Wiebren Tjalma, Konstantinos Papadimitriou","doi":"10.21037/tcr-2026-1303","DOIUrl":"10.21037/tcr-2026-1303","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"660"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931114","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":"Reduced Arpc1b expression in astrocytes is associated with cytoskeletal remodeling, ALDOA redistribution, glycolysis, and neuroinflammation in a mouse model of bone cancer pain.","authors":"Ying Liang, Jiacheng Yu, Mei Li, Yinan Jin, Yue Yao, Kunyu Han, Yulin Huang, Rui Xu, Yanting Mao, Zhengliang Ma","doi":"10.21037/tcr-2026-0836","DOIUrl":"10.21037/tcr-2026-0836","url":null,"abstract":"<p><strong>Background: </strong>Bone cancer pain (BCP) frequently develops following cancerous lesions in the bone, severely affecting patients' daily activities and long-term quality of life. However, effective therapeutic options remain limited. Therefore, it is essential to explore its underlying mechanisms to identify new therapeutic targets.</p><p><strong>Methods: </strong>A mouse model of BCP was established to investigate pain development using the von Frey test. Immunofluorescence staining and Western blotting were performed to detect neuroinflammation and astrocyte activation. Transcriptome sequencing and targeted metabolomics were conducted to identify significantly altered genes and pathways in BCP mice, and the results were validated by Western blotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Small interfering RNA was used to examine the relationship between Arpc1b and ALDOA using the aforementioned methods.</p><p><strong>Results: </strong>Neuroinflammation in the spinal cord of BCP mice was accompanied by activation of C3-positive reactive astrocytes. Sequencing analysis revealed that Arpc1b and glycolysis were associated with C3-positive astrocyte activation. Further experiments demonstrated that BCP-induced neuroinflammation downregulated Arpc1b and increased the expression of glycolytic enzymes in spinal cord astrocytes. Additionally, increased soluble ALDOA appeared to contribute to BCP-induced glycolysis in astrocytes, while Arpc1b-mediated cytoskeletal remodeling increased free ALDOA levels.</p><p><strong>Conclusions: </strong>The significant reduction of Arpc1b in C3-positive astrocytes within the spinal cord of BCP mice mediates cytoskeletal remodeling, causing dissociation of ALDOA from F-actin. This process promotes excessive glycolysis in astrocytes and persistent neuroinflammation, which may underlie BCP.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"637"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931125","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":"STC1 is associated with tumor progression and suppressive niches in laryngeal squamous cell carcinoma.","authors":"Xiaoxue Chen, Wenjing Li, Yiyao Liu, Lei Zhang, Zhigang Zhao, Yue Wang, Linli Tian","doi":"10.21037/tcr-2026-1080","DOIUrl":"10.21037/tcr-2026-1080","url":null,"abstract":"<p><strong>Background: </strong>Laryngeal squamous cell carcinoma (LSCC) exhibits high recurrence and therapy resistance. We aimed to investigate the undefined role of Stanniocalcin-1 (STC1) in LSCC pathogenesis.</p><p><strong>Methods: </strong>The single-cell RNA sequencing (RNA-seq) data and the clinical information of LSCC patients were acquired from the public database. Prognostic differences and diagnostic efficiency of STC1 were assessed. The gene correlation was investigated by Spearman method. Enrichment analysis was performed using clusterProfiler, and immune infiltration was assessed with CIBERSORT. Finally, we analyzed the distribution of specific STC1 expression in cell types using single-cell RNA sequencing (scRNA-seq) analysis, and cell communication for ligand-receptor interactions between STC1⁺ cells and T cell subsets.</p><p><strong>Results: </strong>The upregulated STC1 was linked to tumor metastasis and disease stage in LSCC. It correlated with genes involved in extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance. High STC1 expression was linked to an immunosuppressive microenvironment, with increased M0 macrophages and reduced CD8⁺ T cells, and was positively correlated with the immune checkpoints [programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3)]. Single-cell analysis localized STC1 to epithelial cells, with STC1⁺ epithelial cells showing enriched endoplasmic reticulum (ER) stress, inflammatory signaling, and EMT during carcinogenesis. Cell-cell communication analysis revealed that STC1⁺ epithelial cells engage T cell subsets through more ligand-receptor pairs in the transforming growth factor-beta (TGF-β) and B- and T-lymphocyte attenuator (BTLA) pathways compared to STC1^- epithelial cells.</p><p><strong>Conclusions: </strong>These findings indicate STC1 is strongly correlated with signatures of immune evasion and malignant progression in LSCC, suggesting that targeting STC1 may reprogram the immunosuppressive microenvironment and improve therapeutic outcomes.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"608"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931170","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":"Radiation biomarkers in body fluids: translational perspectives for precision radiotherapy-a narrative review.","authors":"Satoru Monzen, Akihito Kotani, Atsushi Muro, Boyang Zuo, Yasuyo Fukushi, Riki Sakamoto, Andrzej Wojcik, Yasushi Mariya","doi":"10.21037/tcr-2026-0096","DOIUrl":"10.21037/tcr-2026-0096","url":null,"abstract":"<p><strong>Background and objective: </strong>Radiotherapy and radionuclide therapy are essential components of modern cancer treatment. Despite substantial advances in radiation delivery and treatment planning, considerable interindividual variability remains in therapeutic response and radiation-induced toxicity. Conventional monitoring approaches, including imaging and routine laboratory tests, often provide limited insight into early or systemic biological responses. Body fluid-based biomarkers may provide accessible molecular readouts of radiation-induced damage, host response, and treatment-related toxicity. This narrative review summarizes radiation biomarkers detectable in body fluids, with emphasis on oxidative stress and cellular damage markers, circulating RNAs and extracellular vesicles, and metabolomic and lipidomic signatures relevant to precision radiation medicine.</p><p><strong>Methods: </strong>A targeted literature search was conducted using PubMed/MEDLINE and Web of Science. Priority was given to primary experimental and clinical studies reporting specific molecular findings, longitudinal biomarker changes, or associations with treatment response and radiation-induced toxicity.</p><p><strong>Key content and findings: </strong>Ionizing radiation induces oxidative stress, DNA damage, inflammatory signaling, metabolic reprogramming, and intercellular communication, generating measurable signals in blood, plasma, serum, and urine. Oxidative DNA damage products such as 8-hydroxy-2'-deoxyguanosine and γ-H2AX-related responses may reflect cellular injury and toxicity risk. Circulating microRNAs and extracellular vesicle-associated cargo may capture transcriptional responses, bystander signaling, and treatment-related systemic changes. Metabolomic and lipidomic studies have identified multimetabolite signatures associated with radiation exposure and normal tissue toxicity. However, most candidate biomarkers remain exploratory, and clinical implementation is limited by variability in sampling, analytical platforms, normalization, and external validation.</p><p><strong>Conclusions: </strong>Integrated longitudinal assessment of complementary biomarker classes, together with clinical and dosimetric information, may improve toxicity monitoring and treatment personalization. Prospective validation and methodological standardization are required before these biomarkers can support routine treatment adaptation.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"658"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931174","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":"Updating the standard model of care for oropharyngeal cancers-are we there yet?","authors":"Sneha Sethi","doi":"10.21037/tcr-2026-1421","DOIUrl":"10.21037/tcr-2026-1421","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"664"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931083","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":"Drug-tolerant persister cells use conserved adaptive transcriptional programs.","authors":"Yu-Chi Chen, Gavin P Robertson","doi":"10.21037/tcr-2026-1168","DOIUrl":"10.21037/tcr-2026-1168","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"662"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931002","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":"Cancer associated fibroblasts: heterogenous modifiers of treatment response.","authors":"Radhika Aiyappa-Maudsley, Thomas A Hughes","doi":"10.21037/tcr-2026-1122","DOIUrl":"10.21037/tcr-2026-1122","url":null,"abstract":"","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"670"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931105","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":"PDZ-binding kinase promotes ovarian cancer cell proliferation and invasion via <i>CCNB1</i> regulation.","authors":"Guzhanuer Awuti, Jiapo Wang, Yun Lu, Haonan Jiang, Xiaoqing Guo","doi":"10.21037/tcr-2026-1337","DOIUrl":"10.21037/tcr-2026-1337","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ovarian cancer is one of the most lethal gynecological malignancies, characterized by late diagnosis, frequent recurrence, and high mortality. PDZ-binding kinase (PBK), a serine/threonine kinase of the mitogen-activated protein kinase kinase (MAPKK) family, has been implicated in the tumorigenesis of multiple cancers, yet its role in ovarian cancer remains incompletely characterized. This study aimed to investigate the effect of PBK on the proliferation and invasion of ovarian cancer cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The expression of &lt;i&gt;PBK&lt;/i&gt; and cyclin B1 (&lt;i&gt;CCNB1&lt;/i&gt;) in normal ovarian tissues and ovarian cancer tissues was analyzed using online databases including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Kaplan-Meier Plotter. Clinical tissue specimens were collected to detect the expression of PBK and &lt;i&gt;CCNB1&lt;/i&gt; by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was performed to detect PBK messenger RNA (mRNA) expression levels in clinical specimens and cell lines. Western blot was used to detect PBK protein expression in ovarian cancer cell lines. ES2 and A2780 cells with higher PBK expression were selected to construct &lt;i&gt;PBK&lt;/i&gt; knockdown cell lines using lentiviral interference vectors. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were performed to explore the effect of &lt;i&gt;PBK&lt;/i&gt; knockdown on cell proliferation. Transwell assay was used to investigate the effect on cell invasion. The Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analyze &lt;i&gt;PBK&lt;/i&gt;-related pathways and predict &lt;i&gt;CCNB1&lt;/i&gt; as the gene most closely related to &lt;i&gt;PBK&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;PBK was significantly overexpressed in ovarian cancer tissues and cell lines compared with normal controls, and high &lt;i&gt;PBK&lt;/i&gt; expression was associated with poor overall survival (OS) and progression-free survival (PFS). Knockdown of &lt;i&gt;PBK&lt;/i&gt; expression inhibited the proliferation, colony formation, and invasion of ovarian cancer cells. Bioinformatics analysis revealed that &lt;i&gt;CCNB1&lt;/i&gt; was significantly overexpressed in ovarian cancer and high &lt;i&gt;CCNB1&lt;/i&gt; expression was associated with poor OS. &lt;i&gt;CCNB1&lt;/i&gt; was also significantly highly expressed in ovarian cancer tissues as validated by immunohistochemistry and was associated with lymph node metastasis. &lt;i&gt;PBK&lt;/i&gt; and &lt;i&gt;CCNB1&lt;/i&gt; expression showed a significant positive correlation in TCGA ovarian cancer datasets. Knockdown of PBK inhibited CCNB1 expression in ovarian cancer cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;PBK promotes ovarian cancer cell proliferation and invasion. PBK knockdown leads to &lt;i&gt;CCNB1&lt;/i&gt; downregulation. These findings suggest that &lt;i&gt;CCNB1&lt;/i&gt; contributes to PBK-mediated oncogenic effects and identify the &lt;i&gt;PBK-CCNB1&lt;/i&gt; axis as a pot","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"571"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930901","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 machine learning-derived intratumoral heterogeneity-related signature predicts the prognosis for and therapeutic response in patients with skin cutaneous melanoma.","authors":"Feng Ding, Wei Tian, Sarina Bai, Hongmei Jia, Ziying Zhang, Yuchen Jia, Fangxin Zhao, Xingxia Hao, Bing Yi, Lili Niu, Shaojie Zhang","doi":"10.21037/tcr-2026-0801","DOIUrl":"10.21037/tcr-2026-0801","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers for predicting prognosis and therapeutic response in skin cutaneous melanoma (SKCM) remain limited. This study aimed to develop an intratumoral heterogeneity (ITH)-related prognostic signature for SKCM using integrative machine learning.</p><p><strong>Methods: </strong>RNA sequencing (RNA-seq) data from 472 SKCM patients in The Cancer Genome Atlas (TCGA) and 214 patients in the GSE65904 cohort were analyzed. ITH scores were calculated using the DEPTH2 algorithm. Differentially expressed genes (DEGs) were identified between high- and low-ITH groups [|log₂fold change (FC)| ≥1, false discovery rate (FDR) <0.05]. Based on 38 prognostic DEGs identified by univariate Cox regression, we employed an integrative framework of 101 machine learning algorithm combinations to construct prognostic models in the TCGA training cohort. The model with the highest average concordance index (C-index) was validated in the GSE65904 cohort and selected as the prognostic ITH-related signature (PIRS). Associations of the PIRS risk score with tumor mutational burden (TMB), immune cell infiltration, immune checkpoint gene expression, and drug sensitivity were systematically evaluated. Model performance was assessed using receiver operating characteristic (ROC) curves and Cox regression analyses.</p><p><strong>Results: </strong>A 38-gene PIRS was constructed using the plsRcox algorithm. Patients with high PIRS risk scores exhibited significantly poorer overall survival (OS) in both the TCGA and Gene Expression Omnibus (GEO) cohorts. The PIRS was identified as an independent prognostic factor, with area under the curve (AUC) values of 0.779, 0.734, and 0.756 for 1-, 3-, and 5-year survival, respectively. High-risk samples displayed significantly lower TMB (P<0.05), reduced immune and stromal cell infiltration (P<0.001), downregulated immune function, and decreased expression of immune checkpoint genes. Additionally, high- and low-PIRS risk score groups exhibited distinct sensitivity patterns to different classes of targeted agents.</p><p><strong>Conclusions: </strong>The machine learning-derived PIRS robustly predicts prognosis in SKCM patients. Its clinical application is promising for optimizing patient risk stratification and treatment decisions, though further prospective validation is warranted.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"15 8","pages":"604"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930947","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}