Abstract
Renal cell carcinoma (RCC) is a disease characterized by excessive administration complexity because it exhibits extraordinary nonuniformity among distinct molecular subtypes. We herein intended to delineate the metabolic aspects of clear cell RCC (ccRCC) in terms of the gene expression profile. Recent studies have revealed that metabolic variations within tumors are related to the responsiveness to immune checkpoint inhibitor (ICI) therapy and patient prognosis. We used 100 previously reported metabolic (MTB) pathways to quantify the metabolic landscape of the 729 ccRCC patients. Three MTB subtypes were established, and the MTB scores were calculated using principal component analysis (PCA). The high MTB score group had better overall survival (OS) and was associated with higher expression of immune-checkpoint and immune-activity signatures. The opposite was true of the low MTB score group, which may explain the poor prognosis of these patients. Three ICI-treated cohorts or tyrosine kinase inhibitor (TKI) treated cohort proved that patients with higher MTB scores exhibited notable therapeutic benefits and clinical gains. This research explained that the MTB score could be applied as a powerful prognostic indicator and predictive of ICI or TKI therapy. Assessing the MTB scores in a more extended group will facilitate our perception of tumor metabolism and provide guidance for studies on targeted approaches for ccRCC patients.
Highlights
Renal cell carcinoma (RCC) remains in the top 10 most commonly diagnosed malignancies globally [1]
Within three MTB clusters, the C1 cluster is marked by higher level of norepinephrine biosynthesis and vitamin B6 metabolism and possesses a better prognosis with a median follow-up time of 50.7 months (median survival time (MST) not reached)
Given that cells in the tumor microenvironment (TME) closely interact with tumor metabolism, we compared the immune and stromal cell composition in TME among different MTB clusters
Summary
Renal cell carcinoma (RCC) remains in the top 10 most commonly diagnosed malignancies globally [1]. Accounting for 70% of pathologically determined RCC, clear cell renal cell carcinoma (ccRCC) is often histologically marked by enriched lipid and glycogen infiltration [2]. RCC is one of the most investigated and perhaps the representative of human cancers distinguished by metabolic reprogramming which is evident in various systemic manifestations [6, 7]. A number of findings have unveiled various metabolic changes that are directly or indirectly involved throughout cancer development. Despite the widely accepted Warburg effect and glutamine addiction, upregulation of glutamine metabolism and lipid synthesis, and reductive carboxylation actively arises in many RCC cells, which enables tumor cells to swiftly reproduce [8–11]. Researchers have worked on strategies to classify ccRCC patients into different risk groups by tumor metabolic patterns.
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