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Abstract

Glutamate Pyruvate Transaminase 2 Promotes Tumor Metastasis through Mesothelial-Epithelial Transition as a Prognostic Biomarker in Colorectal Cancer

Author(s): Yuhang Luo, Shuke Fei and Xiuda Peng*
Department of General Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China

Correspondence Address:
Xiuda Peng, Department of General Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China, E-mail: xiudapengusc@126.com


The objective of this research is to investigate the prognostic factors and enhance the outlook for patients with colorectal cancer. The possible molecular mechanism affecting the prognosis of colorectal cancer was explored by conducting Kyoto encyclopedia of genes and genomes, gene ontology, and gene set enrichment analysis using glutamate pyruvate transaminase 2 positive and negative associated genes, as well as examining the high and low expression of glutamate pyruvate transaminase 2 in colorectal cancer, according to the Kyoto encyclopedia of genes and genomes. To investigate the potential association between glutamate pyruvate transaminase 2 and epithelial-mesenchymal transition and mesenchymal-epithelial transition, a correlation analysis was conducted utilizing the tumor immune estimation resource database and immunohistochemistry to analyze the relationship between glutamate pyruvate transaminase 2 and epithelial-mesenchymal transition transcription factors. The level of glutamate pyruvate transaminase 2 expressions in colorectal cancer tissues was markedly greater than in non-tumor tissues, and it exhibited a positive correlation with unfavorable prognosis. Furthermore, it was found to be associated with pathological stage, tumor stage and tumor grade. Experimental investigations have demonstrated that increased glutamate pyruvate transaminase 2 expression results in reduced cellular adhesion, alterations in components of the extracellular matrix, and enhancement in both the Wnt/beta catenin signaling pathway and the Notch signaling pathway. In the meantime, the strong association between glutamate pyruvate transaminase 2 and E-cadherin provides justification for the notion that glutamate pyruvate transaminase 2 facilitates the spread of tumors by means of epithelial-mesenchymal transition and mesenchymal-epithelial transition. Glutamate pyruvate transaminase 2 is strongly associated with the unfavorable outcome of colorectal cancer. It controls epithelial-mesenchymal transition to enhance metastasis via the Wnt/beta catenin and Notch pathways, while also facilitating mesenchymal-epithelial transition to support tumor metastasis colonization. These findings establish glutamate pyruvate transaminase 2 as a reliable prognostic biomarker and a promising therapeutic target for metastatic colorectal cancer.

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