Integrated analysis and experiments uncover the function of disulfidptosis in predicting immunotherapy effectiveness and delineating immune landscapes in uterine corpus endometrial carcinoma

• Published in: Frontiers in immunology 2024-10, Vol.15, p.1454730
• Main Authors: Han, Lei, Li, Yilin, Yu, Yanjie, Liu, Guo, Gao, Xiangqian, Wang, Fei, Chen, Weiwei, Xu, Huishu, Zhang, Baolin, Xu, Yingjiang, Pan, Yitong, Huang, Yu, Yi, Ping
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; disulfidptosis; Endometrial Neoplasms - genetics; Endometrial Neoplasms - immunology; Endometrial Neoplasms - pathology; Endometrial Neoplasms - therapy; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunology; immunotherapy; Immunotherapy - methods; LRPPRC; Prognosis; tumor microenvironment; Tumor Microenvironment - immunology; uterine corpus endometrial carcinoma
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1454730

Recently, a novel type of metabolic-regulated cell demise titled disulfidptosis has been discovered. Studies have demonstrated its importance in immune responses against cancer and its impact on the proliferation of cancer cells. Nonetheless, the precise mechanism and roles of disulfidptosis are not fully understood, particularly regarding the prognosis for individuals with uterine corpus endometrial carcinoma (UCEC). In this research, a distinctive disulfidptosis pattern was developed in UCEC, and by utilizing Non-negative Matrix Factorization (NMF) on 23 disulfidptosis related genes within the TCGA database, 3 distinct subgroups were distinguished. To collect data, we acquired gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA and GEO database, specifically from UCEC patients. Cell line experiments and immunohistochemical (IHC) staining were conducted to validate the role of the LRPPRC in proliferation, migration and invasion. The genetic features and immune microenvironment of these subgroups were examined. It is worth mentioning that these subgroups offer important insights into comprehending the tumor microenvironment (TME) and the response of patients to immunotherapy and chemotherapy. Moreover, a disulfidptosis model was developed and validated, demonstrating a high level of accuracy in predicting the prognosis and outcomes of immunotherapy in UCEC patients. Additionally, a novel biomarker, LRPPRC, was identified, which can server as a promising predictor for forecasting prognosis in UCEC patients, with validation through tissue microarray staining and cell line experiments. This study has designed a classification system and a disulfidptosis model for UCEC, in addition to identifying a new biomarker, LRPPRC, for UCEC. These advancements serve as reliable and positive indicators for predicting outcomes and the efficacy of immunotherapy for each UCEC patient.