Discover. Oncology最新文献

{"title":"JAK2 inactivating mutations promotes endometrial cancer progression by targeting HIF-1α.","authors":"Zheng Chen, Xuan Zheng, Weijian Zeng, Juan Wang, Qin Lin","doi":"10.1007/s12672-024-01722-6","DOIUrl":"https://doi.org/10.1007/s12672-024-01722-6","url":null,"abstract":"<p><strong>Objective: </strong>Endometrial cancer (EC) is the ninth most common malignancy among women. While mutations in JAK2 are frequently observed in EC, the specific biological functions of JAK2 in endometrial cancer are poorly understood.</p><p><strong>Methods: </strong>The genetic alterations of JAK2 in different cancer types were explored using sequencing dataset deposited at TCGA database. JAK2 mutations were detected in EC formalin-fixed paraffin-embedded (FFPE) samples using Sanger sequencing. The expression levels of JAK2 was accessed using the TCGA database and immunohistochemistry. Furthermore, the relationships between JAK2 expression and staging and prognosis of EC patients were investigated using the TCGA database. Down-regulation of JAK2 were achieved by transient transfection with short hairpin RNAs (shRNAs). Effects of JAK2 on cancer cells proliferation and migration were evaluated by CCK8, colony formation, and transwell assay. The potential biological functions of JAK2 in EC were identified based on bioinformatics analysis. Effects of JAK2 on expression levels of target genes were detected by RT-qPCR and western blotting. Co-immunoprecipitation (co-IP) assays was used to detect the physical association between JAK2 and HIF-1α.</p><p><strong>Results: </strong>Frequent mutations and down-regulation of JAK2 were found in EC. Loss-of-function (LOF) assays suggested that JAK2 silencing in endometrial cancer cells promoted cell proliferation and migration, which were partially dependent on HIF-1α signaling pathway. Furthermore, our findings demonstrated that JAK2 interacted with HIF-1α and reduced HIF1α protein expression under hypoxia.</p><p><strong>Conclusion: </strong>These findings revealed novel molecular mechanisms underlying JAK2 LOF mutations-driven endometrial tumorigenesis and revealed that the HIF-1α pathway may be a potential therapeutic target in JAK2-mutated endometrial cancer.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"836"},"PeriodicalIF":2.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAMTS12 serves as a novel prognostic biomarker and promotes proliferation and invasion in gastric cancer.","authors":"Ruimei Gao, Yalan Hu, Qiuxiang Yuan","doi":"10.1007/s12672-024-01724-4","DOIUrl":"https://doi.org/10.1007/s12672-024-01724-4","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a prevalent and aggressive malignancy with a poor prognosis. This study aimed to identify diagnostic and prognostic biomarkers while exploring their potential functions in GC. A total of 598 upregulated and 506 downregulated genes were identified in GC patients. Among these, survival-related differentially expressed genes (DEGs), including ADAMTS12, F5, and VCAN, were highlighted. Pan-cancer analyses revealed their dysregulation across multiple tumor types. A novel prognostic signature, incorporating ADAMTS12 and F5, effectively stratified GC patients into low- and high-risk groups, demonstrating significant differences in overall survival and robust predictive performance. ADAMTS12, strongly associated with advanced clinical stages and poor prognosis, was validated in an independent cohort and exhibited promising diagnostic potential. RT-PCR and western blot analyses confirmed its high expression in GC tissues and cell lines. Functional assays further demonstrated that ADAMTS12 promotes GC cell proliferation and invasion. In summary, this study provides critical insights into the molecular landscape of GC, offering a potential prognostic tool and therapeutic target.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"837"},"PeriodicalIF":2.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between gut microbiota and cancer chemotherapy: current status and trends.","authors":"Shanshan Yang, Shaodong Hao, Hui Ye, Xuezhi Zhang","doi":"10.1007/s12672-024-01704-8","DOIUrl":"https://doi.org/10.1007/s12672-024-01704-8","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is crucial in the management of tumors, but challenges such as chemoresistance and adverse reactions frequently lead to therapeutic delays or even premature cessation. A growing body of research underscores a profound connection between the gut microbiota (GM) and cancer chemotherapy (CC). This paper aims to pinpoint highly influential publications and monitor the current landscape and evolving trends within the realm of GM/CC research.</p><p><strong>Methods: </strong>On October 1st, 2024, a comprehensive search for GM/CC publications spanning the past 20 years from 2004 to 2023 was conducted utilizing the Web of Science Core Collection (WoSCC). The scope encompassed both articles and reviews, and the data was subsequently extracted. To gain insights into the evolution and dynamics of this research field, we employed bibliometric analysis tools such as the Bibliometrix R package, VOSviewer, and Microsoft Excel to visualize and analyze various dimensions, including prominent journals, leading authors, esteemed institutions, contributing countries/regions, highly cited papers, and frequently occurring keywords.</p><p><strong>Results: </strong>A total of 888 papers were obtained. The number of publications about GM/CC studies has increased gradually. China and the United States published the largest number of papers. The INSERM was in the leading position in publishers. The most productive authors were Zitvogel L from France. Cancers had the largest number of papers. Citation analysis explained the historical evolution and breakthroughs in GM/CC research. Highly cited papers and common keywords illustrated the status and trends of GM/CC research. Four clusters were identified, and the hot topics included the role of the GM in the efficacy and toxicity of CC, the targeting of the GM to improve the outcome of CC, the mechanism by which the GM affects CC, and the correlation of the GM with carcinogenesis and cancer therapy. Metabolism, GM-derived metabolites, tumor microenvironment, immunity, intestinal barrier, tumor microbiota and Fusobacterium nucleatum may become the new hotspots and trends of GM/CC research.</p><p><strong>Conclusion: </strong>This study analyzed global publications and bibliometric characteristics of the links between GM and CC, identified highly cited papers in GM/CC, provided insight into the status, hotspots, and trends of global GM/CC research, and showed that the GM can be used to predict the efficacy and toxicity of CC and modifying the GM can improve the outcomes of chemotherapeutics, which may inform clinical researchers of future directions.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"833"},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the insulin-like growth factor-1 receptor to overcome imatinib resistance in chronic myeloid leukemia.","authors":"Seiichi Okabe, Yuya Arai, Akihiko Gotoh","doi":"10.1007/s12672-024-01706-6","DOIUrl":"https://doi.org/10.1007/s12672-024-01706-6","url":null,"abstract":"<p><p>Patients with chronic myeloid leukemia (CML) frequently develop resistance to tyrosine kinase inhibitors such as imatinib. In this study, we explored the role of the insulin-like growth factor 1 (IGF-1) signaling pathway in CML and imatinib resistance. An analysis of IGF-1 gene expression using public databases revealed elevated levels of insulin-like growth factor-binding proteins in patients with chronic-phase CML. Further research revealed that IGF-1-related genes were upregulated in patients who were unresponsive to imatinib, suggesting that IGF-1 signaling plays a role in the resistance mechanism. Furthermore, we evaluated the efficacy of linsitinib, a selective insulin-like growth factor-1 receptor (IGF-1R) inhibitor, in inhibiting the growth of CML cell lines, including imatinib-resistant cell lines, and observed a notable decrease in cell viability and an increase in cytotoxicity. The combination of imatinib and linsitinib reduced cell viability and increased caspase-3/7 activity in imatinib-resistant cells. Moreover, silencing of IGF-1R by small interfering ribonucleic acid increased the sensitivity of CML cell lines to imatinib, indicating that IGF-1R could be a strategic target for overcoming resistance. These findings highlight the therapeutic potential of linsitinib and that IGF-1R inhibition may improve the treatment outcomes of patients with imatinib-resistant CML.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"835"},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor profiling for subtype classification and as prognostic markers in 33 cancer types.","authors":"Kazuya Nakamichi, Hironori Suzuki, Yusuke Yamamoto, Kentaro Semba, Jun Nakayama","doi":"10.1007/s12672-024-01732-4","DOIUrl":"https://doi.org/10.1007/s12672-024-01732-4","url":null,"abstract":"<p><p>Nuclear receptors, a group of 48 transcription factors that regulate a multitude of processes within our body, have long been employed as diagnostic markers or therapeutic targets in breast cancer, prostate cancer, and acute promyelocytic leukemia. Unfortunately, no comprehensive investigation has been conducted on their significance in other cancer types. The current study aimed to explore novel diagnostic markers by classifying nuclear receptors according to their expression patterns based on transcriptome data from The Cancer Genome Atlas on 10,071 tumor samples across 33 cancer types and investigating their association with genetic mutations, histological types, and prognosis. Our analysis showed that 21 cancers, including breast cancer, can be classified into distinct clusters based on their nuclear receptor expression profiles. Moreover, significant differences in overall survival were observed in 9 of the 21 cancer types. Overall, the results of this study indicate that previously overlooked nuclear receptors, such as NR0B1 in lung adenocarcinoma, may prove beneficial in the diagnosis of several cancers.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"834"},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RASGEF1C as a novel prognostic biomarker for LUAD.","authors":"Jinlong Liu, Xiaoying Liu, Yingou Zeng, Di Qiao, Bin Dai, Yunlong Wu, Meng Wang, Qiang Wang","doi":"10.1007/s12672-024-01718-2","DOIUrl":"https://doi.org/10.1007/s12672-024-01718-2","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a common histologic lung cancer with high morbidity and mortality, and most patients have distant metastases at diagnosis. RasGEF Domain Family Member 1C (RASGEF1C) could regulated Alzheimer's disease. However, its function in various cancers, including LUAD, is poorly understood. In the present study, we discovered that high expression of RASGEF1C in LUAD was associated with poorer prognosis, unfavorable histological features, and poorer pathological staging. In addition, RASGEF1C expression was an independent predictor of overall survival, disease specific survival, and progress free interval in patients with LUAD. High expression of RASGEF1C was linked to signaling pathways that are involved in the immune response and cell proliferation, according to KEGG enrichment analysis. Additionally, we verified that RASGEF1C was highly expressed in LUAD cell lines and that RASGEF1C knockdown dramatically decreased the capacity of LUAD cell lines to invade, migrate, and proliferate. Our research provides mechanistic insights into the function of RASGEF1C in the progression of LUAD and suggests that RASGEF1C is a prospective target for future therapy.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"825"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and imaging characteristics of intraductal papillary neoplasms of the breast: a prospective trial.","authors":"Yingjiao Wang, Yuechong Li, Yang Qu, Yidong Zhou, Qiang Sun, Songjie Shen","doi":"10.1007/s12672-024-01681-y","DOIUrl":"https://doi.org/10.1007/s12672-024-01681-y","url":null,"abstract":"<p><strong>Background: </strong>Intraductal papillary neoplasms (IPNs) often have a similar clinical and imaging presentation, making them difficult to diagnose. We designed this study to refine and compare intraductal papillary neoplasms' clinical and imaging characteristics.</p><p><strong>Methods: </strong>This study included a total of 154 patients with a postoperative diagnosis of IPNs and collected their clinical, imaging, and pathological data. We compared the clinical and imaging characteristics of benign, atypical hyperplasia, and malignant lesions. We also compared the diagnostic efficacy of ultrasound and mammography.</p><p><strong>Results: </strong>The mean age of malignant patients was 57 years old, which was significantly higher than that in the other groups (48 years in the benign group and 47 years in the atypical hyperplasia group). The proportion of patients with malignant lesions clinically presenting as palpable masses (31.3%) was significantly higher than that of benign lesions (8.6%) (P < 0.05). The proportion of malignant lesions presenting in the periphery (≥ 3 cm from the nipple) was 40.6% compared to 22.4% for benign (P < 0.05). In ultrasonography, characteristics that showed statistically significant differences between benign and malignant lesions were the shape of the mass and calcification (P < 0.05). On mammography, differences were found in mass shape, calcification, and density of masses and glands (P < 0.05).</p><p><strong>Conclusions: </strong>Clinical features such as age, symptoms, lesion location, and imaging characteristics such as shape, calcification, mass, and density may help to differentiate the classifications of IPNs.</p><p><strong>Trial registration: </strong>This study was registered at ClinicalTrials.gov on 12/06/2020 (identifier: NCT04429269).</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"831"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of cell cycle and p53 signaling pathways related genes in breast, colorectal, lung, and pancreatic cancers: implications for prognosis and drug sensitivity for therapeutic potential.","authors":"Jiyauddin Khan, Priyanjana Ghosh, Urmi Bajpai, Kountay Dwivedi, Daman Saluja","doi":"10.1007/s12672-024-01712-8","DOIUrl":"https://doi.org/10.1007/s12672-024-01712-8","url":null,"abstract":"<p><p>Cancer, a leading cause of death worldwide, is projected to increase by 76.6% in new cases and 89.7% in mortality by 2050 (WHO 2022). Among various types, lung cancer is the most prevalent with high morbidity, while breast, colorectal, and pancreatic cancers also show high mortality rates. Cancer progression often involves disruption in cell cycle regulation and signaling pathways, with mutations in genes like TP53, EGFR, and K-RAS playing significant roles. In this study, we analyzed gene expression datasets to identify common molecular signatures across breast, colorectal, lung and pancreatic cancers. Our focus was on genes related to cell cycle regulation and p53 signaling pathway, intending to discover potential biomarkers for improved diagnosis and treatment strategies. The study analyzed GEO datasets; GSE45827, GSE9348, GSE30219, and GSE62165 for breast, colorectal, lung, and pancreatic cancers respectively. Differentially expressed genes (DEGs) were identified using GEO2R, and functional annotation and pathway analysis were performed using WebGestalt. Common cell cycle and p53 signaling genes were acquired from MSigDB using GSEA. A protein-protein interaction network was constructed using STRING and Cytoscape, identifying top hub genes. Validation of hub genes at mRNA and protein levels was done via GEPIA2 and Human Protein Atlas. Survival analysis was conducted using TCGA data by GEPIA2 and LASSO, and drug sensitivity was analyzed with the GSCA drug bank database, highlighting potential therapeutic targets. The study identified 411 common DEGs among these four cancers. Pathway and functional enrichment revealed key biological processes and pathways like p53 signaling, and cell cycle. The intersection of these DEGs with genes involved in cell cycle and p53 signaling, identified 23 common genes that were used for constructing a PPI network. The top 10 hub genes were validated both for mRNA and protein expression, revealing they are significantly overexpressed in all studied cancers. Prognostic relevance showed that MCM4, MCM6, CCNA2, CDC20, and CHEK1 are associated with survival. Additionally, drug sensitivity analysis highlighted key gene-drug interactions, suggesting potential targets for therapeutic intervention.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"832"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the shared pathways and common biomarkers in cervical and ovarian cancer using integrated bioinformatics analysis.","authors":"Fang Liu, Min Wang, Tian Zhu, Cong Xu, Guangming Wang","doi":"10.1007/s12672-024-01725-3","DOIUrl":"https://doi.org/10.1007/s12672-024-01725-3","url":null,"abstract":"<p><strong>Objective: </strong>Searching for potential biomarkers and therapeutic targets for early diagnosis of gynecological tumors to improve patient survival.</p><p><strong>Methods: </strong>Microarray datasets of cervical cancer (CC) and ovarian cancer (OC) were downloaded from the Gene Expression Omnibus (GEO) database, then, differential gene expression between cancerous and normal tissues in the datasets was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to screen for co-expression modules associated with CC and OC. The screened shared genes were then further analyzed for functional pathway enrichment. Next, the least absolute shrinkage and selection operator (LASSO) with tenfold cross validation is used to further screened for common diagnostic biomarkers for the two diseases, and further validation is performed using two independent GEO datasets. Finally, the CIBERSORT algorithm was used to estimate the immune infiltration levels of CC and OC, and the correlation between immune cell infiltration and common biomarkers was explored.</p><p><strong>Results: </strong>After crossing the common DEGs detected by \"Limma\" R package with the common module genes identified by WGCNA, 44 shared genes were obtained. Functional enrichment indicates that these shared genes are mainly related to DNA synthesis pathways. Lasso regression analysis revealed that EFNA1, TYMS, and WISP2 were co-diagnostic markers for CC and OC, and then based on their expression levels and diagnostic efficacy, EFNA1 was selected as the best co-marker for CC and OC. Immune infiltration analysis shows that the immune environment has a significant impact on the occurrence and development of CC and OC, and the expression of EFNA1 is related to changes in immune cells. Gene-drug interaction analyses identified 27 common drug compounds that interact with candidate genes.</p><p><strong>Conclusion: </strong>This study adopted bioinformatics methods to investigate the common pathways and identify diagnostic markers between CC and OC, suggesting that DNA synthesis and immune environment are closely related to the occurrence and development of CC and OC. EFNA1 may be a potential diagnostic indicator and therapeutic target for patients with CC and OC.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"826"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based identification of histone deacetylase-associated prognostic factors and prognostic modeling for low-grade glioma.","authors":"Keshan Wen, Weijie Zhu, Ziyi Luo, Wei Wang","doi":"10.1007/s12672-024-01713-7","DOIUrl":"https://doi.org/10.1007/s12672-024-01713-7","url":null,"abstract":"<p><strong>Background: </strong>Low-grade glioma (LGG) is a slow-growing but invasive tumor that affects brain function. Histone deacetylases (HDACs) play a critical role in gene regulation and tumor progression. This study aims to develop a prognostic model based on HDAC-related genes to aid in risk stratification and predict therapeutic responses.</p><p><strong>Methods: </strong>Expression data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed to identify an optimal HDAC-related risk signature from 73 genes using 10 machine learning algorithms. Patients were stratified into high- and low-risk groups based on the median risk score. Prognostic accuracy was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were performed to explore pathways linked to the gene signature. Immune infiltration and tumor microenvironment characteristics were assessed using Single Sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE algorithm. SubMap was applied to predict responsiveness to immune checkpoint inhibitors, and chemotherapeutic sensitivity was analyzed via the Genomics of Drug Sensitivity in Cancer (GDSC) database.</p><p><strong>Results: </strong>A prognostic model consisting of four HDAC-related genes-SP140, BAZ1B, SP100, and SIRT1-was identified. This signature displayed strong prognostic accuracy, achieving a C-index of 0.945. Individuals with LGG were systematically divided into high-risk and low-risk cohorts based on the median risk value, enabling more precise risk stratification. The survival prognosis was significantly worse in the high-risk cohort compared to the low-risk group, highlighting distinct survival trajectories. Notably, the two cohorts exhibited marked shifts in immune checkpoint gene transcriptional profiles and immune cell infiltration maps, underscoring fundamental biological differences that contribute to these differing prognoses.</p><p><strong>Conclusion: </strong>We developed an HDAC-related four-gene prognostic model that correlates with survival, immune landscape, and therapeutic response in LGG patients. This model may guide personalized treatment strategies and improve prognostic accuracy, warranting further validation in clinical settings.</p>","PeriodicalId":11148,"journal":{"name":"Discover. Oncology","volume":"15 1","pages":"824"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}