Discover. Oncology最新文献

{"title":"Global research trends and emerging hotspots of immune checkpoint inhibitors in gastric cancer from 2015 to 2025.","authors":"Zhongting Lu, Anqi Wang, Xiangnv Meng, Peng He, Tao Li, Jing Chen","doi":"10.1007/s12672-026-05710-w","DOIUrl":"https://doi.org/10.1007/s12672-026-05710-w","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have emerged as an important therapeutic strategy for gastric cancer. However, the rapid expansion of related research has made it challenging to comprehensively understand its developmental patterns and emerging directions. This study aimed to systematically evaluate research trends and hotspots in ICIs for gastric cancer using bibliometric methods.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in the Web of Science Core Collection, covering publications from January 1, 2015, to October 28, 2025. Bibliometric analysis was performed using CiteSpace, VOSviewer, and Scimago Graphica to assess publication trends, collaborative networks, influential authors and journals, co-cited references, and keyword evolution.</p><p><strong>Results: </strong>A total of 1440 publications were included. The overall research output exhibited a sustained growth trend. Global collaboration networks were dominated by a limited number of core countries and institutions. Keyword and reference analyses revealed that major research hotspots evolved from clinical efficacy validation to biomarker-driven precision stratification and, more recently, to tumor microenvironment modulation and combination therapy strategies.</p><p><strong>Conclusions: </strong>This bibliometric analysis provides a structured overview of the research landscape of ICIs in gastric cancer. The findings highlight the progressive shift of research focus toward precision immunotherapy and mechanistic exploration, offering insights that may inform future basic and clinical research.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789504","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 five-gene TAM and MYCN signature predicts prognosis and identifies MTHFD2 as a therapeutic target in neuroblastoma.","authors":"Yanhua Huang, Ziyang Gao, Wenqiang Liang, Zhenchao Su, Yuemei Mo, Huangjian Wu","doi":"10.1007/s12672-026-05456-5","DOIUrl":"10.1007/s12672-026-05456-5","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages (TAMs) are key components of the tumor immune-suppressive microenvironment. However, studies focusing on the modulation of TAM-specific gene signatures to improve neuroblastoma (NB) prognosis are limited. MYCN amplification (MNA) is known to influence the immune landscape in neuroblastoma.</p><p><strong>Methods: </strong>Single-cell sequencing of 19 NB samples and transcriptome data from 498 NB samples were analyzed to identify macrophage-specific genes associated with poor NB prognosis. A risk signature was constructed by integrating differentially expressed genes (DEGs) related to TAMs and MYCN using univariate Cox regression, LASSO regression, and Kaplan-Meier survival analysis. Single-factor and multi-factor Cox regression analyses were conducted to explore the relationship between clinical characteristics and prognosis, and a nomogram was constructed. The impact of downregulating TAM target genes in macrophages was explored using CCK8, EdU incorporation, and Transwell assays.</p><p><strong>Results: </strong>A signature based on five macrophage-related genes associated with NB prognosis (FCGR3A, ATF5, MTHFD2, HMGA1, and LY6E) was successfully established and validated for its strong prognostic predictive performance (AUC: 0.829). A clinically applicable Nomogram incorporating these genes was also developed. CCK-8 assays revealed a time-dependent inhibitory effect on neuroblastoma cell proliferation upon co-culture with MTHFD2-knockdown macrophages. EdU and Transwell assays showed that downregulation of MTHFD2 in macrophages significantly reduced the invasive and migratory capabilities of NB cells, particularly in MYCN-amplified cells.</p><p><strong>Conclusion: </strong>We developed and validated a five-gene signature based on TAM and MYCN-related genes with strong prognostic performance. Downregulation of MTHFD2 in macrophages reduced neuroblastoma cell proliferation, invasion, and migration, particularly in MYCN-amplified cells, highlighting MTHFD2 as a potential therapeutic target in high-risk patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668793","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":"Integrated multi-omic and functional profiling reveals a ZDHHC16-associated palmitoylation-proteostasis state in hepatocellular carcinoma.","authors":"Lihua Zhang, Xiaolei Zhang, Caiqi Liu, Xiaofei Xin, Xinchi Luan, Jialin Song, Wensheng Qiu","doi":"10.1007/s12672-026-05700-y","DOIUrl":"10.1007/s12672-026-05700-y","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.</p><p><strong>Methods: </strong>Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.</p><p><strong>Results: </strong>ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank P = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.</p><p><strong>Conclusions: </strong>Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976083","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":"Novel curcumin derivative DMC-GF suppresses glioblastoma growth by targeting MAPK1 and TRIM21 to modulates STAT3/AKT phosphorylation.","authors":"Ming Xia, Lei Shi, Xue-Tao Li, Yu-Lun Huang, Zhi-Min Wang","doi":"10.1007/s12672-026-05204-9","DOIUrl":"https://doi.org/10.1007/s12672-026-05204-9","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains a therapeutic challenge with a poor prognosis, necessitating novel treatment strategies. This study investigated the anti-tumor efficacy of a novel demethoxycurcumin derivative, DMC-GF, against GBM. Both in vitro assays and an orthotopic xenograft model demonstrated that DMC-GF significantly suppressed GBM cell proliferation, induced apoptosis, and potently inhibited tumor growth in vivo. Mechanistically, DMC-GF was found to target MAPK1 and interact with TRIM21, thereby modulating the phosphorylation of the STAT3/AKT signaling axis and triggering the mitochondrial apoptotic pathway. Furthermore, integrated metabolomic and transcriptomic analyses identified the regulation of mitochondrial oxidative phosphorylation as a central event in the therapeutic mechanism of DMC-GF. In conclusion, DMC-GF exerts its anti-glioblastoma effects primarily by inducing mitochondrial apoptosis via suppression of the phosphorylated STAT3/AKT pathway, positioning it as a promising therapeutic candidate.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788741","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":"ATR inhibition enhances radiosensitivity in p53-deficient colorectal cancer cells.","authors":"Na Shen, Rui Zong, Jie Li, Xuemei Liu","doi":"10.1007/s12672-026-05692-9","DOIUrl":"10.1007/s12672-026-05692-9","url":null,"abstract":"<p><p>Radiosensitizers that improve tumor-cell responses to radiation without increasing normal-tissue toxicity are needed in colorectal cancer (CRC). We investigated whether inhibition of ataxia telangiectasia and Rad3-related (ATR) kinase by VE-822 (berzosertib) enhances radiation response and whether p53 status is associated with the magnitude of response. HCT116 (p53 wild type), HT29 (p53 mutant), and HCT116 cells with siRNA-mediated p53 knockdown (HCT116 KD) were treated with VE-822 with or without ionizing radiation (RT). Short-term cell viability and long-term clonogenic survival were evaluated. DNA-damage signaling and ATR-pathway activity were assessed by analysis of γH2AX and phosphorylated CHK1, whereas flow cytometry was used to examine cell-cycle distribution, mitotic entry, and apoptosis. VE-822 IC50 values were 80.8 nM for HCT116, 33.6 nM for HT29, and 19.6 nM for HCT116 KD cells. A low concentration of VE-822 (20 nM, administered 1 h before RT) had minimal effects in HCT116 cells but reduced viability and clonogenic survival in HCT116 KD cells, particularly when combined with RT. VE-822 reduced pCHK1 and was associated with sustained γH2AX signaling, with more pronounced effects in HCT116 KD cells. At 24 h after RT, HCT116 cells predominantly accumulated in G1 with modest apoptosis, whereas HCT116 KD cells showed greater G2/M accumulation and apoptosis after VE-822 plus RT. Increased phospho-Histone H3 positivity after combined treatment was consistent with increased mitotic entry. These in vitro findings suggest that impaired p53 function is associated with increased sensitivity to combined ATR inhibition and irradiation and support further evaluation of p53 status as a candidate response biomarker.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864016","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":"Pan-cancer analysis identifies ODF2 as a dual prognostic and predictive biomarker for immunotherapy.","authors":"Wei Guo, Ling Ran, Xiangyang Shao, Yuan Tian, Ranran Shi","doi":"10.1007/s12672-026-05694-7","DOIUrl":"10.1007/s12672-026-05694-7","url":null,"abstract":"<p><strong>Background: </strong>Transforming immunologically \"cold\" tumors into inflamed \"hot\" remains a primary hurdle in cancer immunotherapy. Cancer-testis antigens (CTAs) represent highly promising targets for next-generation therapeutic cancer vaccines and adoptive cell therapies. However, the systemic immunogenomic landscape and prognostic significance of Outer Dense Fiber 2 (ODF2), an emerging CTA, across human malignancies remain largely unexplored. This study comprehensively decodes the pan-cancer immunological and prognostic characteristics of ODF2 to evaluate its broad-spectrum clinical utility.</p><p><strong>Methods: </strong>Multi-omics and clinical data from the TCGA, GTEx, and HPA databases were analyzed to assess the prognostic value of ODF2. Gene Set Enrichment Analysis (GSEA) was performed to identify associated biological pathways. The correlation between ODF2 expression, immune cell infiltration, and immune checkpoints was evaluated using multiple deconvolution algorithms. The predictive value of ODF2 for immune checkpoint blockade (ICB) therapy was assessed using independent clinical cohorts from the BEST database.</p><p><strong>Results: </strong>ODF2 is significantly upregulated across multiple solid tumors and correlates with poor clinical outcomes. GSEA revealed that high ODF2 expression is strongly enriched in cell cycle and oncogenic pathways. Furthermore, ODF2 expression exhibits positive correlation with immunosuppressive cell populations and major inhibitory immune checkpoints, while inversely correlating with infiltrating CD8⁺ T cells. ROC analyses demonstrated that ODF2 expression reliably predicts clinical responsiveness to anti-PD-1 and anti-CTLA-4 therapies in diverse clinical cohorts.</p><p><strong>Conclusions: </strong>ODF2 is strongly associated with an immunosuppressive TME and serves as a predictive biomarker for ICB efficacy. Rather than definitively validating it as a universal target, these findings provide a theoretical rationale for investigating ODF2 as a potential candidate for next-generation peptide vaccines and adoptive T-cell therapies to overcome ICB resistance.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886726","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":"High expression of CD74 is associated with poor prognosis and tumor immune infiltration in Acute Myeloid Leukemia.","authors":"Yixi Chen, Zihan Zhang, Ruotong Li, Shun Ding, Xinbao Hao, Yinglian Pan","doi":"10.1007/s12672-026-05640-7","DOIUrl":"10.1007/s12672-026-05640-7","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the expression patterns of the CD74 gene in Acute Myeloid Leukemia (LAML), its clinical prognostic significance, and its association with the tumor microenvironment (TME).</p><p><strong>Methods: </strong>Data from public databases, including TCGA and GTEx, were integrated to analyze the differences in CD74 expression between LAML tissues and normal controls; perform subgroup analysis based on clinical and pathological characteristics; evaluate its prognostic value using survival analysis and ROC curves; elucidate its potential immune regulatory mechanisms through the CIBERSORT algorithm and functional enrichment analysis.</p><p><strong>Results: </strong>CD74 was significantly overexpressed in LAML tissues, with higher expression observed in the monocyte-derived subtypes (M4-M7) and in patients with high white blood cell counts (P < 0.05). High CD74 expression is significantly associated with poor overall survival in patients with LAML(P < 0.01). Immunohistochemical analysis revealed that CD74 expression was positively correlated with the abundance of memory B cells, monocytes, and M2 macrophages, and was primarily enriched in antigen-presenting and immune response pathways.</p><p><strong>Conclusion: </strong>High CD74 expression is associated with poor prognosis in patients with LAML and may promote disease progression by reshaping the immune microenvironment; it holds promise as a new prognostic marker and immunotherapy target.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886682","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":"Construction of a risk model based on folate metabolism-related genes to predict prognosis and immunological characteristics of stomach adenocarcinoma.","authors":"Liu He, Lilei Zhuang, Shenbao Wu","doi":"10.1007/s12672-026-05648-z","DOIUrl":"10.1007/s12672-026-05648-z","url":null,"abstract":"<p><strong>Background: </strong>Given the substantial disease burden of stomach adenocarcinoma (STAD)-the dominant and lethal subtype of gastric cancer-and the pivotal role of folate metabolism reprogramming in malignancy and treatment response, this study aimed to construct a prognostic model utilizing folate metabolism-related genes (FMRGs). Such a model is urgently required to supplement traditional TNM staging and to guide personalized precision medicine.</p><p><strong>Methods: </strong>Interrogation of TCGA and GEO transcriptomic profiles enabled the identification of differentially expressed FMRGs. These genes subsequently facilitated the construction of a prognostic signature via LASSO-Cox regression, which was then subjected to external validation. We further evaluated the clinical relevance of this risk signature by exploring its correlations with the tumor immune microenvironment, immunotherapy efficacy, and drug sensitivity, employing CIBERSORT and ssGSEA analytical frameworks.</p><p><strong>Results: </strong>A five-gene prognostic model established from 220 FMRGs demonstrated moderate prognostic performance in identifying high-risk stomach adenocarcinoma patients with poorer survival. The high-risk group exhibited immunosuppressive microenvironments with stromal activation, while the low-risk group demonstrated \"hot\" tumor phenotypes characterized by higher immunogenicity and superior responses to immunotherapy and chemotherapy. Consequently, this model serves as a robust independent prognostic indicator.</p><p><strong>Conclusion: </strong>This five-gene folate metabolism signature shows moderate prognostic value in STAD and may help inform future investigations of the tumor immune microenvironment and therapeutic stratification.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590749","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":"Correction: Moesin silencing enhances the radiosensitivity of glioblastoma by inhibiting DNA damage repair via CD44/AKT1 signaling pathway.","authors":"Xin Ding, Yan Wang, Zhiying Shao, Xin Wen, Bo Wang, Gongzhen Liu, Chang Xu, Luyijie Chai, Hui Qiu, Longzhen Zhang","doi":"10.1007/s12672-026-05577-x","DOIUrl":"10.1007/s12672-026-05577-x","url":null,"abstract":"","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590780","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":"Identification of disulfidptosis-related molecular subtypes in pleural mesothelioma demonstrates a correlation with the immune infiltration, prognosis and therapy efficacy.","authors":"Jing Ding, Xuefeng Huang, Wenxiu Yao, Tongyu Lin","doi":"10.1007/s12672-026-05557-1","DOIUrl":"10.1007/s12672-026-05557-1","url":null,"abstract":"<p><strong>Background: </strong>Pleural mesothelioma (PM) is a rare and aggressive malignancy with increasing incidence, high mortality, and limited treatment options. Disulfidptosis, a newly identified form of regulated cell death, may play an important role in cancer, but its relevance in PM remains unclear.</p><p><strong>Methods: </strong>Transcriptomic and clinical data of PM were obtained from public databases. PM was classified into molecular subtypes based on disulfidptosis-related genes (DRGs). We then compared prognosis, tumor microenvironment, metabolic features, predicted response to immune checkpoint blockade, and chemotherapy sensitivity between subtypes. In addition, a prognostic signature was established, and key genes were identified using random survival forest analysis.</p><p><strong>Results: </strong>Two novel DRG-defined molecular subtypes were identified in PM. The DRGs-high subtype (Cluster 2) was associated with significantly worse overall survival, an immunosuppressive microenvironment dominated by M2 macrophages, and a lower predicted likelihood of response to immune checkpoint blockade. In contrast, the DRGs-low subtype (Cluster 1) showed metabolic reprogramming toward glycolysis and fatty acid oxidation, increased NK cell infiltration, and reduced sensitivity to chemotherapy. An 11-gene prognostic signature demonstrated predictive performance, with an AUC of 0.95 for 5-year survival (95%CI 0.881-1.013). Random survival forest analysis identified LMNB2 and CDCA2 as key genes, both of which were highly expressed in tumor tissues.</p><p><strong>Conclusions: </strong>PM can be classified into two DRG-defined molecular subtypes with distinct prognostic, immune, and metabolic features. These findings provide insights into PM heterogeneity and may support future studies on therapeutic stratification. The prognostic signature remains exploratory and requires validation in independent external cohorts before clinical application.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789475","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}