Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma

作者：Hansen Lin, Liangmin Fu, Pengju Li, Jiangquan Zhu, Quanhui Xu, Yinghan Wang, Mukhtar Adan Mumin, Xinwei Zhou, Yuhang Chen, Guannan Shu, G YAO, Minyu Chen, Jun Lü, Lizhen Zhang, Yujun Liu, Yiqi Zhao, Jiahao Bao, Wei Chen, Junhang Luo, Xiaofei Li, Zhenhua Chen, Jiazheng Cao · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-04161-z · 被引用次数：41 · 研究领域：Cancer, Lipids, and Metabolism、Ferroptosis and cancer prognosis、Renal cell carcinoma treatment

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a highly invasive and metastatic subtype of kidney malignancy and is correlated with metabolic reprogramming for adaptation to the tumor microenvironment comprising infiltrated immune cells and immunomodulatory molecules. The role of immune cells in the tumor microenvironment (TME) and their association with abnormal fatty acids metabolism in ccRCC remains poorly understood. METHOD: RNA-seq and clinical data of KIRC from The Cancer Genome Atlas (TCGA) and E-MTAB-1980 from the ArrayExpress dataset. The Nivolumab group and Everolimus group of the CheckMate 025 study, the Atezolizumab arm of IMmotion150 and the Atezolizumab plus Bevacizumab group of IMmotion151 cohort were obtained for subsequent analysis. After differential expression genes identification, the signature was constructed through univariate Cox proportional hazard regression and simultaneously the least absolute shrinkage and selection operator (Lasso) analysis and the predictive performance of our signature was assessed by using receiver operating characteristic (ROC), Kaplan-Meier (KM) survival analysis, nomogram, drug sensitivity analysis, immunotherapeutic effect analysis and enrichment analysis. Immunohistochemistry (IHC), qPCR and western blot were performed to measure related mRNA or protein expression. Biological features were evaluated by wound healing, cell migration and invasion assays and colony formation test and analyzed using coculture assay and...