Expression and Clinical Significance of Lactate Dehydrogenase A in Colon Adenocarcinoma

Yutong Wang,Zhiming Liao,Zhijie Xu,Xiaoyun He,Jianhua Zhou,Chunlin Ou,Hui Nie

doi:10.3389/fonc.2021.700795

Abstract

Lactate dehydrogenase A (LDHA) is an important glycolytic enzyme that promotes glycolysis and plays a crucial role in cancer cell invasion and immune infiltration. However, the relevance of LDHA in colon adenocarcinoma (COAD) remains unclear. In this study, we analyzed the correlation between the expression of LDHA and clinicopathological characteristics in COAD using immunohistochemistry analysis, and then used integrative bioinformatics analyses to further study the function and role of LDHA in COAD. We found that LDHA was highly expressed in COAD tissues compared with adjacent normal tissues, and that COAD patients with high LDHA expression levels showed poor survival. In addition, LDHA expression was closely associated with the immune infiltrating levels of CD8+ T cells, neutrophils, and dendritic cells. Our findings highlight the potential role of LDHA in the tumorigenesis and prognosis of COAD. Furthermore, our results indicate that COAD is a novel immune checkpoint in the diagnosis and treatment of COAD.

Highlights

Colon adenocarcinoma (COAD) is a class of colorectal cancer (CRC) and the second leading cause of cancer-related deaths worldwide [1, 2]
Gene set enrichment analysis (GSEA) revealed that Lactate dehydrogenase A (LDHA) was significantly highly expressed in colon adenocarcinoma (COAD) compared with non-tumor tissues according to the GSE9348 and GSE23878 datasets
The results showed that LDHA expression was significantly elevated in breast invasive carcinoma, COAD, esophageal carcinoma, head and neck cancer, kidney renal clear cell carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, rectum adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma compared with adjacent normal tissues, and decreased in kidney chromophobe, which established that there was a high LDHA expression in COAD (Figure 1B)

Summary

Introduction

Colon adenocarcinoma (COAD) is a class of colorectal cancer (CRC) and the second leading cause of cancer-related deaths worldwide [1, 2]. A large number of studies have shown that the COAD tumor progression can be controlled by regulating the key factors involved in glycolysis [6,7,8]. Several studies have shown that LDHA expression is abnormally high in LDHA and Colon Adenocarcinoma various cancers such as liver cancer, breast cancer, and oral squamous cell carcinoma, and it is closely related to the malignant progression [12,13,14]. It was reported that the high expression of LDHA was related to tumor volume, stage, and degree of cell differentiation and affected the disease-free survival (DFS) and overall survival (OS), which is an important indication for clinical diagnosis [15, 16]. The relationship between LDHA and the clinicopathological characteristics of patients with colon cancer as well as its role in the immune response of COAD has rarely been reported

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