Mitochondrial pyruvate carrier 1: a novel prognostic biomarker that predicts favourable patient survival in cancer

Abstract

Mitochondrial pyruvate carrier 1 (MPC1) is a key metabolic protein that regulates the transport of pyruvate into the mitochondrial inner membrane. MPC1 deficiency may cause metabolic reprogramming. However, whether and how MPC1 controls mitochondrial oxidative capacity in cancer are still relatively unknown. MPC1 deficiency was recently found to be strongly associated with various diseases and cancer hallmarks. We utilized online databases and uncovered that MPC1 expression is lower in many cancer tissues than in adjacent normal tissues. In addition, MPC1 expression was found to be substantially altered in five cancer types: breast-invasive carcinoma (BRCA), kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and prostate adenocarcinoma (PRAD). However, in KIRC, LUAD, PAAD, and PRAD, high MPC1 expression is closely associated with favourable prognosis. Low MPC1 expression in BRCA is significantly associated with shorter overall survival time. MPC1 expression shows strong positive and negative correlations with immune cell infiltration in thymoma (THYM) and thyroid carcinoma (THCA). Furthermore, we have comprehensively summarized the current literature regarding the metabolic reprogramming effects of MPC1 in various cancers. As shown in the literature, MPC1 expression is significantly decreased in cancer tissue and associated with poor prognosis. We discuss the potential metabolism-altering effects of MPC1 in cancer, including decreased pyruvate transport ability; impaired pyruvate-driven oxidative phosphorylation (OXPHOS); and increased lactate production, glucose consumption, and glycolytic capacity, and the underlying mechanisms. These activities facilitate tumour progression, migration, and invasion. MPC1 is a novel cancer biomarker and potentially powerful therapeutic target for cancer diagnosis and treatment. Further studies aimed at slowing cancer progression are in progress.

Keywords: Cancer; Glycolytic; MPC1; Metabolic reprogramming.

Fig. 1

Basic information on MPC1. a The genomic location of the MPC1 gene. b The subcellular location of MPC1 (mainly mitochondrial). c Proteins that interact with MPC1

Fig. 2

The function of MPC1 in mitochondria. Oestrogen-related receptor-alpha (ERR-α) activates the proximal MPC1 promoter through PGC-1α, thus causing MPC1 overexpression. PGC-1α promotes MPC1 expression, enhancing pyruvate transport and OXPHOS activity

Fig. 3

MPC1 deficiency facilitates tumour progression, migration, and invasion

Fig. 4

MPC1 is differentially expressed in various cancers. a Comparison of MPC1 expression levels in cancer tissues and normal tissues via the Oncomine database. b The mRNA expression level in different tumours according to the TIMER2.0 analysis of TCGA data (*P < 0.05, **P < 0.01, ***P < 0.001)

Fig. 5

Prognostic analysis of high and low MPC1 expression in various cancers. a Survival curves of OS in the KIRC cohort. b Survival curves of OS in the LUAD cohort. c Survival curves of OS in the PAAD cohort. d Survival curves of OS in the PRAD cohort. e Survival curves of OS in the BRCA cohort

Fig. 6

The association of MPC1 expression with immune infiltration. a MPC1 expression and the immune infiltration landscape in 26 cancers. b MPC1 expression is positively associated with tumour purity and immune cell infiltration in THYM. c MPC1 expression is negatively associated with tumour purity and immune cell infiltration in THCA