Discover. Oncology最新文献

{"title":"Visualization analysis of breast cancer-related ubiquitination modifications over the past two decades.","authors":"Yongxiang Li, Yiyang Wang, Yubo Jing, Youseng Zhu, Xinzhu Huang, JunYi Wang, Elihamu Dilraba, Chenming Guo","doi":"10.1007/s12672-025-02032-1","DOIUrl":"10.1007/s12672-025-02032-1","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitination is a type of post-translational modification, referring to the process in which the small molecular protein ubiquitin covalently binds to target proteins under the catalysis of a series of enzymes. The process of ubiquitination is vital in the onset and progression of breast cancer. The use of the ubiquitin-protease system is expected to be a new way to treat human breast cancer. This research aimed to investigate the evolution patterns, key areas of interest, and future directions of ubiquitination in breast cancer via bibliometric analysis.</p><p><strong>Methods: </strong>Research articles on ubiquitination modifications in breast cancer were sourced from the Web of Science Core Collection database and analyzed via Microsoft Excel 2021, Bibliometrix, VOSviewer, and Citespace software for thorough bibliometrics.</p><p><strong>Results: </strong>From 2005-2024, 1850 English articles published in 405 journals by 1842 institutions/universities from 61 countries were included in the study. Keywords, research fields, co-cited literature and other information were included. Research on ubiquitination modifications has focused on breast cancer, expression, protein, activation, degradation, ubiquitination, phosphorylation, etc. Notably, the keywords that broke out in the past five years have focused on \"triple-negative breast cancer\", \"promotion\", and \"metabolism\". These findings suggest that key areas of current research are metabolism, immunity, survival, and prognosis in triple-negative breast cancer.</p><p><strong>Conclusions: </strong>Our findings indicate that research on triple-negative breast cancer, as well as its immunological and metabolic aspects, is a burgeoning and promising area. Our work offers valuable guidance and fresh perspectives on the relationship between breast cancer and ubiquitin modification.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"431"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751318","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":"Investigation of new autoantibodies in urothelial bladder cancer for biomarker discovery using immunoproteomics.","authors":"Samira Tabaei, Mohammadrasul Zareinejad, Mohammad Reza Haghshenas, Nasser Shakhssalim, Kambiz Gilany, Allan Stensballe, Abbas Ghaderi","doi":"10.1007/s12672-025-02167-1","DOIUrl":"10.1007/s12672-025-02167-1","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated antigens (TAAs) lead to the production of tumor-specific autoantibodies (anti-TAA autoantibodies) by triggering the humoral immune system which can be used as candidate biomarkers. This study aims to investigate TAAs proteins eliciting humoral responses in different stages of urothelial bladder carcinoma (UBC) using an immunoproteomics approach to find novel biomarkers for the clinical management of the disease.</p><p><strong>Methods: </strong>Total proteins were obtained from the newly established UBC cell line, JAM-ICR, and separated by two-dimensional gel electrophoresis (2DE). These proteins were then immobilized using pooled serum samples from healthy individuals, autoimmune and UBC patients at different stages. The immunoreactive spots in UBC patient samples were identified by mass spectrometry and verified with several databases such as GEPIA and Enrichr databases.</p><p><strong>Results: </strong>Through the comparison of the immunoreactivity pattern of serums, we were able to identify eight specific proteins using LC-MS. Patients with muscle invasion showed increased expression of ENO1, VDAC2, AKR1B1, SDF2L1, PRDX6, PSME1, HSPB1 and PHB1 compared to controls. In addition, non-muscle invasive patients showed overexpression of ENO1, VDAC2, AKR1B1, and PRDX6 compared to controls. In addition to their diagnostic function, PRDX6, ENO1, VDAC2, and PHB1 have been demonstrated to possess prognostic capabilities in patients with UBC. Interestingly, these proteins were mainly associated with cellular growth and anti-apoptotic activity.</p><p><strong>Conclusion: </strong>In this study, eight anti-TAA autoantibodies were identified that have the potential to serve as diagnostic and prognostic biomarkers. These could represent a valuable panel of biomarkers for the management of UBC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"436"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751292","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":"Research progress on the signaling pathway mechanism of terpenoids against breast cancer.","authors":"Sheng-Nan Tu, Fen Hu, Juan Zhang, Haifeng Cai, Junquan Yang","doi":"10.1007/s12672-025-01881-0","DOIUrl":"10.1007/s12672-025-01881-0","url":null,"abstract":"<p><p>Breast cancer is the most common malignant tumor in women worldwide. Current treatments include chemotherapy, hormone therapy, radiotherapy and surgery. Terpenoids have great anti-cancer potential due to their anti-inflammatory, antioxidant, anti-tumor, antiviral and other biological activities. They have become the central drug for the prevention and treatment of breast cancer. However, their low bioavailability and stability are urgent issues that need to be addressed. This article aims to sort out the mechanism of action of terpenoids in the treatment of breast cancer. By reviewing different signal transduction pathways, it is hoped that new ideas for the joint action of multiple pathways and multiple targets will be provided, and a theoretical basis will be provided for improving basic research and clinical treatment of breast cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"433"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751313","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":"Assessing the effect of modifiable risk factors on hepatocellular carcinoma: evidence from a bidirectional Mendelian randomization analysis.","authors":"Lijuan Wei, Enci Ding, Dongyan Lu, Zhongying Rui, Jie Shen, Guoju Fan","doi":"10.1007/s12672-025-02177-z","DOIUrl":"10.1007/s12672-025-02177-z","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of hepatocellular carcinoma (HCC) involves a variety of environmental risk factors, some of which have yet to be fully clarified. Using the Mendelian randomization (MR) approach, this study comprehensively investigates the causal effect of genetically predicted modifiable risk factors on HCC.</p><p><strong>Methods: </strong>Genetic variants related to the 50 risk factors that had been identified in previous research were derived from genome-wide association studies. Summary statistics for the discovery cohort and validation cohort of HCC were sourced from the FinnGen consortium and the UK Biobank, respectively. Bidirectional MR analysis and sensitivity analysis were performed to establish causative risk factors for HCC.</p><p><strong>Results: </strong>Through the inverse variance weighted method, the results of the discovery cohort indicated that waist circumference, nonalcoholic fatty liver disease (NAFLD), alanine aminotransferase (ALT) levels, and aspartate aminotransferase (AST) levels were significantly linked to HCC occurrence risk. Furthermore, body fat percentage, glycated hemoglobin (HbA1c), obesity class 1-3, waist-to-hip ratio, iron, ferritin, transferrin saturation, and urate had suggestive associations with HCC. The validation cohort further confirmed that NAFLD and ALT levels were strongly related to HCC. Reverse MR indicated that genetic susceptibility to HCC was connected to NAFLD and transferrin saturation. Sensitivity analyses showed that most of the findings were robust.</p><p><strong>Conclusion: </strong>This MR study delivers evidence of the complex causal relationship between modifiable risk factors and HCC. These findings offer new insights into potential prevention and treatment strategies for HCC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"437"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751146","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":"Exploring the association between 91 circulating inflammatory proteins and the risk of carcinoid syndrome: a Mendelian randomization analysis.","authors":"Jingzhi Wang, Simin Peng","doi":"10.1007/s12672-025-02147-5","DOIUrl":"10.1007/s12672-025-02147-5","url":null,"abstract":"<p><p>This study aims to explore the potential correlation between circulating inflammatory proteins and carcinoid syndrome (CS). Using summary data from genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) analysis with two samples, treating 91 circulating inflammatory proteins as exposure factors and CS as the outcome. Based on genetic loci closely associated with circulating inflammatory proteins selected as instrumental variables, we primarily employed the inverse-variance weighted (IVW) method for analysis, combined with the weighted median method (WM), simple median method (SM), weighted mode estimation (WME), and MR-Egger regression for comprehensive analysis. Initial IVW results revealed significant causal effects of six circulating inflammatory proteins on CS. Specifically, Interleukin-17C levels were negatively correlated with CS risk, indicating a protective effect; whereas beta-nerve growth factor, C-C motif chemokine 20, Natural killer cell receptor 2B4, C-X-C motif chemokine 5, and Leukemia inhibitory factor levels were positively correlated with CS risk, suggesting detrimental effects. In heterogeneity tests, the selected single-nucleotide polymorphisms (SNPs) did not show heterogeneity, and analysis using Egger intercept and MR-PRESSO test did not detect pleiotropy of SNPs, thus validating the reliability of the study. Furthermore, sensitivity analysis using the leave-one-out method further confirmed the robustness of the results. In summary, this study identified significant causal relationships between six inflammatory proteins-Interleukin-17C, beta-nerve growth factor, C-C motif chemokine 20, Natural killer cell receptor 2B4, C-X-C motif chemokine 5, and Leukemia inhibitory factor-and CS risk through MR analysis. This finding not only emphasizes the important role of inflammation in the pathogenesis of CS but also suggests the potential value of inflammatory proteins as targets for early diagnosis and therapeutic interventions.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"434"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751195","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":"Anticancer activity of Stemona tuberosa (wild asparagus) against type-II human lung adenocarcinoma (A549) cells and identification of SRC inhibitor using integrated network pharmacology and molecular dynamic simulation.","authors":"C Lalmuansangi, Lalfakawmi, Fanai Nghakliana, Hmingremhlua Sailo, Lalchhandami Tochhawng, Amit Kumar Trivedi, Kiran R Kharat, Balachandar Vellingiri, Nachimuthu Senthil Kumar, Zothan Siama","doi":"10.1007/s12672-025-02138-6","DOIUrl":"10.1007/s12672-025-02138-6","url":null,"abstract":"<p><p>Stemona tuberosa is widely recognized for its traditional applications as an anti-cancer agent. This study aimed to assess the anti-cancer properties of S. tuberosa in human lung adenocarcinoma A549 cells. Among the various solvent extracts of S. tuberosa, the methanolic extract showed the highest toxicity against A549 cells. The S. tuberosa extract elicited cytotoxic effects and suppressed colony formation in A549 cells in a dose-dependent manner. S. tuberosa activity was further supported by AO/EtBr staining, increased caspase 3/6 activity, upregulation of pro-apoptotic genes, DNA damage, and elevated lipid peroxidation, with decreasing antioxidant levels. LC-MS analysis identified 80 predominant secondary metabolites in the methanolic extracts of S. tuberosa. A network pharmacology study identified SRC as the primary target of compounds identified from S. tuberosa. SRC protein is crucial for advancing lung cancer because of its function in cell proliferation, survival, and metastasis. Among the various compounds identified from S. tuberosa extract, 4-Azatricyclo [4.3.1.13,8] undecan-5-one (ADE) (- 10.88 kcal/mol) and Dihydro-normorphine, 3-desoxy- (DNY) (- 10.83 kcal/mol) exhibited notable binding affinities for SRC. Further analysis using molecular dynamics simulations (100 ns) validated the stability of SRC-ligand complexes, with RMSD of 1.8 and 2.2 Å for ADE and DNY, respectively, alongside the establishment of essential hydrogen bonds with pivotal residues, including ASP408, ALA403, and THR438. Finally, gmx._MMPBSA showed favourable ΔGbind values for ADE (- 15.06 ± 0.11 kcal/mol) and DNY (- 15.66 ± 0.25 kcal/mol), which highlights the significant potential of ADE and DNY as effective SRC inhibitors, suggesting S. tuberosa as a novel candidate for cancer therapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"429"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751751","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 a long non-coding RNA signature associated with cuproptosis for prognosis and immunotherapy response prediction in patients with lung adenocarcinoma.","authors":"Jie Zeng, Zhenyu Wu, Meijuan Luo, Zhibo Chen, Xie Xu, Guijing Xie, Quhai Chen, Wenjie Bai, Gang Xiao, Jianjiang Xie","doi":"10.1007/s12672-025-02092-3","DOIUrl":"10.1007/s12672-025-02092-3","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, exhibits high heterogeneity due to molecular variations. Cuproptosis is a newly discovered type of cell death that is linked to copper metabolism and long non-coding RNAs (lncRNAs) may play a significant role in this process. We conducted a comprehensive analysis of lncRNA related to cuproptosis and identified a CRLscore to predict the prognosis and immune landscape for LUAD patients.</p><p><strong>Methods: </strong>The LUAD patient cohort obtained from TCGA database was divided into training and validation sets. A range of statistical methods were employed to identify lncRNAs associated with cuproptosis. Multivariate Cox regression was then utilized to develop the CRLscore, which was further used to construct and evaluate a nomogram. Additionally, we investigated the biological functions, gene mutations, and immune landscape.</p><p><strong>Results: </strong>A CRLscore, comprising six cuproptosis-related lncRNAs, was developed to stratify patients into high- and low-risk groups. The CRLscore demonstrated its ability to independently predict prognosis in both the training set and the validation set. Utilizing the CRLscore, we constructed a nomogram that exhibited favorable predictive efficiency. Furthermore, the cuproptosis-related lncRNAs exhibited associations with important signaling pathways such as p53 signaling, MYC Targets V1, and G2M Checkpoint. Notably, the CRLscore displayed substantial differences in somatic mutations and immune landscape. Finally, qRT-PCR results showed the significant differential expression of five cuproptosis-related lncRNAs between LUAD and normal cells.</p><p><strong>Conclusion: </strong>The CRLscore could serve as a potential prognostic indicator and may predict the response to immunotherapy in LUAD patients.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"432"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751287","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":"Prognostic implications of alternative splicing events and key splicing factors in head and neck squamous cell carcinoma.","authors":"Siyi He, Jiali Meng, Chunyan Liang, Yiru Wang, Xinling Qin, Lulu Huang, Rensheng Wang, Weimei Huang","doi":"10.1007/s12672-025-02214-x","DOIUrl":"10.1007/s12672-025-02214-x","url":null,"abstract":"<p><p>The incidence of head and neck squamous cell carcinoma (HNSCC) remains high, accompanied by low 5-year survival rates. Identifying prognostic factors is essential for advancing personalized treatment approaches. Increasing evidence implicates aberrant alternative splicing (AS) plays a key role in tumor progression. Utilizing data from TCGA and TCGA SpliceSeq, prognosis-associated AS events were identified through Cox regression analysis. A prognostic risk model was developed via multivariate Cox and LASSO regression, with validation conducted using Kaplan-Meier survival analysis and ROC curve analysis. The correlation between splicing factors (SFs) and prognosis-associated AS events was analyzed using Pearson's method, followed by the construction of an SF-AS regulatory network. Key splicing factors (KSFs) were identified using Cytoscape software. Expression of KSFs in HNSCC was confirmed by quantitative PCR and Western blotting. SiRNA-mediated knockdown in HNSCC cell lines (HONE1, HN4, SAS) demonstrated effects on cell proliferation, invasion, and migration, as assessed by CCK8, colony formation, Transwell, and wound healing assays. Tumor growth was further evaluated in a subcutaneous tumor model in vivo. A total of 2347 survival-related AS events were identified, of which eleven were used to construct the prognostic model. Patients in the low-risk group exhibited significantly improved outcomes (P = 0e + 00), underscoring the model's predictive accuracy. Notably, DDX39B and PRPF39 emerged as key splicing factors, exhibiting high expression in HNSCC and correlating with poor prognosis, positioning them as potential biomarkers and therapeutic targets.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"430"},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751302","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":"Emerging strategies and translational advancements of DDR1 in oncology.","authors":"Yuxi Luo, Tianxin Liu, Jinli Pei, Shengnan Xu, Jie Liu, Jinming Yu","doi":"10.1007/s12672-025-02107-z","DOIUrl":"10.1007/s12672-025-02107-z","url":null,"abstract":"<p><p>Discoidin domain receptor 1 (DDR1) has emerged as a promising therapeutic target in oncology due to its unique role in tumor-stroma interactions and its involvement in key signaling pathways that drive cancer progression. DDR1 is homologous to the transmembrane receptor tyrosine kinase (RTK) family and uniquely requires binding to collagen for its activation. It regulates several cellular processes related to tumor cell proliferation, metabolism, migration, stromal remodeling, and epithelial-mesenchymal transition (EMT), ultimately influencing patient survival. Dysregulation of DDR1 may contribute to cancer progression, neurodegenerative diseases, fibrotic conditions, and atherosclerosis. Moreover, DDR1 has been shown to affect a wide variety of cancers, including lung, breast, stomach, colon, ovarian, and pancreatic cancers, underscoring its potential as a therapeutic target. Various small-molecule tyrosine kinase inhibitors aimed at DDR1 have been developed and have demonstrated significant effectiveness in reducing tumor growth. This review focuses on the structure, function, and mechanism of DDR1, as well as its involvement in cancer progression. Additionally, it examines the development and therapeutic potential of DDR1 inhibitors, offering a comprehensive overview of their application in cancer treatment. By synthesizing current knowledge, this article provides valuable insights to guide future research and innovation in targeting DDR1 for clinical therapeutic advancement.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"428"},"PeriodicalIF":2.8,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751189","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":"Intratumor heterogeneity related signature for clinical outcome and immunotherapy advantages in lung adenocarcinoma.","authors":"Yanhua Zuo, Li Lin, Libo Sun","doi":"10.1007/s12672-025-02173-3","DOIUrl":"10.1007/s12672-025-02173-3","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy benefits shows discrepancy in different lung adenocarcinoma (LUAD) patients because of the intratumor heterogeneity (ITH). ITH favors tumor evolution and correlated with drug resistance. The genes mediating ITH in LUAD and their role in predicting prognosis and therapy benefits is unclear.</p><p><strong>Methods: </strong>An ITH-related signature (IRS) was built by ten methods-based integrative machine learning programs using TCGA, GSE68571, GSE42127, GSE30129, GSE50081, GSE72094, GSE37745, GSE68467, and GSE31210 dataset. To assess the relationship between IRS and the tumor immune microenvironment, numerous prediction scores were employed.</p><p><strong>Results: </strong>The optimal predictive signature for LUAD cases was the IRS developed using Lasso + stepCox(both) method, which had the highest average C-index of 0.80. It performed consistently and effectively in predicting the clinical outcomes of LUAD patients. Additionally, compared to the clinical stage and numerous other existing prediction models, a higher C-index was demonstrated in IRS. LUAD patients with low IRS score had a higher level of immuno-activated cells, higher TMB score, lower ITH score, higher PD1&CTLA4 immunophenoscore, and tumor escape score in LUAD. The gene set score for angiogenesis, coagulation, hypoxia, and NOTCH signaling were increased in LUAD with high IRS score.</p><p><strong>Conclusion: </strong>Overall, the study developed a unique IRS for LUAD that may serve as a predictor of the clinical outcome and immunotherapy advantages for individuals with LAUD.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"16 1","pages":"425"},"PeriodicalIF":2.8,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742551","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}