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Construction of a lactate-related prognostic signature for predicting prognosis, tumor microenvironment, and immune response in kidney renal clear cell carcinoma.
Front. Immunol. 13:818984 (2022)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Kidney Renal Clear Cell Carcinoma ; Lactate ; Nomogram ; Prognostic Signature ; Tumor Microenvironment; Gene; Identification; Phosphorylase; Immunotherapy; Inhibitor; Discovery; Promote; Target; Tool
ISSN (print) / ISBN
1664-3224
e-ISSN
1664-3224
Journal
Frontiers in Immunology
Quellenangaben
Volume: 13,
Article Number: 818984
Publisher
Frontiers
Publishing Place
Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
Shandong Key Research and Development Program, China