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Research Paper|Volume 16, Issue 2|pp 1021—1048

Potential prognosis and immunotherapy predictor TFAP2A in pan-cancer

Chenxi Niu1, Haixuan Wen1, Shutong Wang2, Guang Shu1, Maonan Wang1, Hanxi Yi1, Ke Guo3, Qiong Pan4, Gang Yin1,5,6
  • 1Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
  • 2Xiangya Medical School, Central South University, Changsha, China
  • 3Department of Neurology, The Third Xiangya Hospital of Central South University, Changsha, China
  • 4Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, China
  • 5China-Africa Research Center of Infectious Diseases, School of Basic Medical Sciences, Central South University, Changsha, China
  • 6National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
* Equal contribution
Received: August 2, 2023Accepted: October 12, 2023Published: January 23, 2024
https://doi.org/10.18632/aging.205225

Copyright: © 2024 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: TFAP2A is critical in regulating the expression of various genes, affecting various biological processes and driving tumorigenesis and tumor development. However, the significance of TFAP2A in carcinogenesis processes remains obscure.

Methods: In our study, we explored multiple databases including TCGA, GTEx, HPA, cBioPortal, TCIA, and other well-established databases for further analysis to expound TFAP2A expression, genetic alternations, and their relationship with the prognosis and cellular signaling network alternations. GO term and KEGG pathway enrichment analysis as well as GSEA were conducted to examine the common functions of TFAP2A. RT-qPCR, Western Blot and Dual Luciferase Reporter assay were employed to perform experimental validation.

Results: TFAP2A mRNA expression level was upregulated and its genetic alternations were frequently present in most cancer types. The enrichment analysis results prompted us to investigate the changes in the tumor immune microenvironment further. We discovered that the expression of TFAP2A was significantly associated with the expression of immune checkpoint genes, immune subtypes, ESTIMATE scores, tumor-infiltrating immune cells, and the possible role of TFAP2A in predicting immunotherapy efficacy. In addition, high TFAP2A expression significantly correlated with several ICP genes, and promoted the expression of PD-L1 on mRNA and protein levels through regulating its expression at the transcriptional level. TFAP2A protein level was upregulated in fresh colon tumor tissue samples compared to that in the adjacent normal tissues, which essentially positively correlated with the expression of PD-L1.

Conclusions: Our study suggests that targeting TFAP2A may provide a novel and effective strategy for cancer treatment.