Deciphering the tumour microenvironment of clear cell renal cell carcinoma: Prognostic insights from programmed death genes using machine learning

• Published in: Journal of cellular and molecular medicine 2024-07, Vol.28 (13), p.e18524-n/a
• Main Authors: Tu, Hongtao, Hu, Qingwen, Ma, Yuying, Huang, Jinbang, Luo, Honghao, Jiang, Lai, Zhang, Shengke, Jiang, Chenglu, Lai, Haotian, Liu, Jie, Chen, Jianyou, Guo, Liwei, Yang, Guanhu, Xu, Ke, Chi, Hao, Chen, Haiqing
• Format: Article
• Language: English
• Subjects: Algorithms; Apoptosis; Apoptosis - genetics; Biomarkers; Biomarkers, Tumor - genetics; cancer biomarkers; Cancer therapies; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cell death; Cell interactions; Cell migration; Cholecystokinin; Clear cell-type renal cell carcinoma; Clinical outcomes; Datasets; drug screen; Fatalities; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomes; Humans; Invasiveness; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Machine Learning; Medical prognosis; Metastases; Nomograms; Original; Patients; Prognosis; programmed cell death; Regression analysis; Sensitivity analysis; Single-Cell Analysis - methods; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors; tumour microenvironment; urologic tumours
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18524

Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late‐stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death‐Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single‐cell data enabled Programmed Cell Death‐Related scoring, subsequent pseudo‐temporal and cell–cell communication analyses. A PCDRGs signature was established using TCGA‐KIRC data. External validation in the arrayexpress cohort underscored the model's superiority over traditional clinical features. Furthermore, our single‐cell analysis unveiled the roles of PCDRG‐based single‐cell subgroups in ccRCC, both in pseudo‐temporal progression and intercellular communication. Finally, we performed CCK‐8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients.