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. 2021 Dec;12(1):3850-3863.
doi: 10.1080/21655979.2021.1951928.

Comprehensive Analysis of Monocarboxylate Transporter 4 (MCT4) expression in breast cancer prognosis and immune infiltration via integrated bioinformatics analysis

Chen Yuan  1 , Jie Zhang  1 , Jianjuan Lou  1 , Siqi Wang  1 , Yanni Jiang  1 , Feiyun Wu  1 , Shouju Wang  1
Affiliations

Comprehensive Analysis of Monocarboxylate Transporter 4 (MCT4) expression in breast cancer prognosis and immune infiltration via integrated bioinformatics analysis

Chen Yuan et al. Bioengineered. 2021 Dec.

Abstract

Lactate blunts the anticancer immune response in breast cancer (BC). However, little is known about the exact effect of lactate transporters such as monocarboxylate transporter 4 (MCT4) on immunotherapy. In this study, we investigated the expression status and prognostic value of MCT4 in BC through large-scale transcriptome data. Our results showed that MCT4 was overexpressed in BC, particularly in the basal-like molecular subtype. Overexpression of MCT4 was significantly correlated with high BC lesion grade and poor prognosis. Enrichment analysis indicated that the MCT4-related genes were involved in immune- and metabolism-related bioprocesses, such as myeloid leukocyte activation, the adaptive immune system, and catabolic process. We also found that the expression of MCT4 in BC lesions was associated with immune cell infiltration and glycolytic rate-limiting enzymes like pyruvate kinase M2 (PKM2) and hexokinases-3 (HK3). Our observations indicate that MCT4 may play a pivotal role in the maintenance of the tumor immune microenvironment (TIME) through metabolic reprogramming. The enzymes of the glycolysis pathway (MCT4, PKM2, and HK3) may thus serve as new targets to modulate the TIME and enhance immunotherapy efficiency.[Figure: see text].

Keywords: Breast cancer; hexokinases-3; immune infiltration; monocarboxylate transporter 4; pyruvate kinase m2.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1.
Figure 1.
The expression profiles of MCT1 and MCT4 in tumor and normal tissues
Figure 2.
Figure 2.
The expression pattern of MCT4 in different subtypes of BC using the GOBO dataset (n = 1881)
Figure 3.
Figure 3.
The expression profile of MCT4 in different subtypes of BC using the merged microarray datasets (n = 10,001)
Figure 4.
Figure 4.
MCT4 expression signature from RNA-seq level exploiting merged RNA-seq datasets (n = 4712)
Figure 5.
Figure 5.
The kaplan-meier survival curves of high and low MCT4 expression in BC through the kaplan-meier plotter database. the RFS in (a) PR+ BC, (b) PR- BC, (c) ER+ BC, (d) ER- BC, (e) HER2+ BC, (f) HER2- BC, (g) basal-like subtype, (h) luminal A subtype, (i) luminal B subtype. RFS: relapse-free survival; HR: hazard ratio
Figure 6.
Figure 6.
The kaplan-meier survival curves of high and low MCT4 expression in BC through the bc-GenExMiner v4.5
Figure 7.
Figure 7.
The biological functions of MCT4 showed in enrichment results
Figure 8.
Figure 8.
The relationship of MCT4 and immune infiltration in BC
Figure 9.
Figure 9.
The intersection of MCT4 related genes and central carbon metabolism related genes
Figure 10.
Figure 10.
The relationship of MCT4, PKM2, and HK3
Figure 11.
Figure 11.
The expression signatures of (a) HK3 and (b) PKM2 in GOBO (n = 1,881)
None
See this image and copyright information in PMC

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