Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent primary malignancies with high heterogeneity in the urological system. Growing evidence implies that lactate is a significant carbon source for cell metabolism and plays a vital role in tumor development, maintenance, and therapeutic response. However, the global influence of lactate-related genes (LRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response has not been comprehensively elucidated in patients with KIRC. In the present study, we collected RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TCGA), E-MTAB-1980, and GSE22541 cohorts. Unsupervised clustering of 17 differentially expressed LRG profiles divided the samples into three clusters with distinct immune characteristics. Three genes (FBP1, HADH, and TYMP) were then identified to construct a lactate-related prognostic signature (LRPS) using the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. The novel signature exhibited excellent robustness and predictive ability for the overall survival of patients. In addition, the constructed nomogram based on the LRPS-based risk scores and clinical factors (age, gender, tumor grade, and stage) showed a robust predictive performance. Furthermore, patients classified by risk scores had distinguishable immune status, tumor mutation burden, response to immunotherapy, and sensitivity to drugs. In conclusion, we developed an LRPS for KIRC that was closely related to the immune landscape and therapeutic response. This LRPS may guide clinicians to make more precise and personalized treatment decisions for KIRC patients.
Frontiers in immunology. 2022 Feb 17*** epublish ***
Zhuolun Sun, Wen Tao, Xudong Guo, Changying Jing, Mingxiao Zhang, Zhenqing Wang, Feng Kong, Ning Suo, Shaobo Jiang, Hanbo Wang
Department of Urology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Institute of Diabetes and Regeneration, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.