Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma

ABSTRACT

Introduction: Clear cell renal cell carcinoma (ccRCC) is a metabolic disease, of which the incidence rate is increasing worldwide. Renal carcinoma is characterized by mutations in target genes involved in metabolic pathways. Metabolic reprogramming covers different processes such as aerobic glycolysis, fatty acid metabolism, and the utilization of tryptophan, glutamine, and arginine. In the era of the multi-omics approach (with integrated transcriptomics, proteomics, and metabolomics), discovering biomarkers for early diagnosis is gaining renewed importance.

Areas covered: In this review, we discuss the pathophysiological mechanisms underlying ccRCC metabolic reprogramming. In addition, we describe the emerging metabolomics-based biomarkers differentially expressed in ccRCC and the rationale for the recently developed drugs specifically targeting the ccRCC metabolome.

Expert opinion: A number of metabolic pathways will be explored in future years, and many of these pathways are potential therapeutic targets and may serve as diagnostic and prognostic biomarkers of ccRCC.

KEYWORDS:

• Renal cell carcinoma
• metabolomics
• metabolism
• NDUFA4L2
• kynurenine
• biomarker

Article Highlights

• ccRCC is a metabolic disease, characterized by genetic mutations in targets involved in metabolic pathways. ccRCC metabolic reprogramming covers different processes, such as aerobic glycolysis, tryptophan, glutamine, arginine, and fatty acids metabolism.

• ccRCC metabolic reprogramming allows tumor cells to survive in conditions of energy deprivation and hypoxia, to synthesize building blocks (proteins, DNA, membranes) for proliferation, and to escape host immunosurveillance and counteract oxidative stress.

• Altered levels of the biochemical enzymes, substrates, metabolic intermediates and final products derived from the metabolic reprogramming can be used as diagnostic biomarkers.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported in part by a grant from ‘Fondazione Cassa di Risparmio di Puglia’ to Rossana Franzin.