Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas

作者全名："Song, Daqiang; Yang, Qian; Li, Liuying; Wei, Yuxian; Zhang, Chong; Du, Huimin; Ren, Guosheng; Li, Hongzhong"

作者地址："[Song, Daqiang; Li, Liuying; Zhang, Chong; Ren, Guosheng; Li, Hongzhong] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China; [Song, Daqiang] Chongqing Med Univ, Dept Pharm, Chongqing, Peoples R China; [Yang, Qian] Chongqing Med Univ, Affiliated Hosp 1, Clin Mol Med Testing Ctr, Chongqing, Peoples R China; [Wei, Yuxian; Ren, Guosheng] Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing, Peoples R China; [Zhang, Chong] Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, Chongqing, Peoples R China; [Du, Huimin] Chongqing Med Univ, Affiliated Hosp 1, Dept Oncol, Chongqing, Peoples R China"

通信作者："Ren, GS; Li, HZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China.; Ren, GS (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001189674000001

JCR分区：Q1

影响因子：5.7

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：prognosis; biomarker; immunotherapy; gliomas

摘要："Background Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy.Methods We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves.Results The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas.Conclusion Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas."

基金机构：National Natural Science Foundation of China10.13039/501100001809

基金资助正文：No Statement Available