Bioinformatics Analysis and Verification of Metabolic Abnormalities in Esophageal Squamous Carcinoma


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Abstract

Background:Although esophageal carcinoma (EC) is one of the most common cancers in the world, details of its pathogenesis remain unclear. Metabolic reprogramming is a main feature of EC. Mitochondrial dysfunction, especially the decrease in mitochondrial complex I (MTCI), plays an important role in the occurrence and development of EC.

Objective:The objective of the study was to analyze and validate the metabolic abnormalities and the role of MTCI in esophageal squamous cell carcinoma.

Methods:In this work, we collected transcriptomic data from 160 esophageal squamous carcinoma samples and 11 normal tissue samples from The Cancer Genome Atlas (TCGA). The OmicsBean and GEPIA2 were used to conduct an analysis of differential gene expression and survival in clinical samples. Rotenone was used to inhibit the MTCI activity. Subsequently, we detected lactate production, glucose uptake, and ATP production.

Results:A total of 1710 genes were identified as being significantly differentially expressed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis suggested that these differentially expressed genes (DEGs) were significantly enriched in various pathways related to carcinoma tumorigenesis and progression. Moreover, we further identified abnormalities in metabolic pathways, in particular, the significantly low expression of multiple subunits of MTCI genes (ND1, ND2, ND3, ND4, ND4L, ND5, and ND6). Rotenone was used to inhibit the MTCI activity of EC109 cells, and it was found that the decrease in MTCI activity promoted HIF1A expression, glucose consumption, lactate production, ATP production, and cell migration.

Conclusion:Our results indicated the occurrence of abnormal metabolism involving decreased mitochondrial complex I activity and increased glycolysis in esophageal squamous cell carcinoma (ESCC), which might be related to its development and degree of malignancy.

About the authors

Duo Tang

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Guozhen Wang

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life,, Beijing University of Technology

Email: info@benthamscience.net

Zijia Liu

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Yu Chen Zheng

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Chao Sheng

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Biqi Wang

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Xiaonan Hou

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Yu Chen Zhang

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Mengfei Yao

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Email: info@benthamscience.net

Zhixiang Zhou

Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology

Author for correspondence.
Email: info@benthamscience.net

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