Special issue “The advance of solid tumor research in China”: Multi‐omics analysis based on 1311 clear cell renal cell carcinoma samples identifies a glycolysis signature associated with prognosis and treatment response

Abstract

In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8+ effector T cells, epithelial‐to‐mesenchymal transition and pan‐fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression‐free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.

Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma

“…Metabolic reprogramming is widespread in malignant tumors, the most well-known of which is glucose metabolic reprogramming that is termed the “Warburg effect” ( 7 ). This inefficient form of energy metabolism supplies the need for new proliferating cancer cells and enables the use of intermediate products to yield biomolecules, such as amino acids, and nucleotides ( 8 ). Previous studies revealed that amino acids could have impacts on cell proliferation, the tumor microenvironment, epigenetic modification, and drug resistance ( 9 – 14 ).…”

Deciphering the role of miR-187-3p/LRFN1 axis in modulating progression, aerobic glycolysis and immune microenvironment of clear cell renal cell carcinoma

“…The rapid development of the field of immunometabolism provides a good prospect for tumor immunotherapy targeting metabolism [47][48][49]. Therefore, exploring the underlying mechanisms of glycolytic metabolism-driven tumor development and TAM regulation of the immune microenvironment is of great significance for preventing tumor metastasis, overcoming acquired immune resistance, and improving efficacy [50]. These novel findings allow researchers to clearly elucidate the pathological significance of the high expression of a key disease-related factor miR-187-3p in ccRCC cells, and to explore the molecular mechanism of miR-187-3p that mediates the malignant biological behavior and immuneinfiltrating TIME of ccRCC cells through LRFN1.…”