Research Paper Volume 16, Issue 2 pp 1021—1048
Potential prognosis and immunotherapy predictor TFAP2A in pan-cancer
- 1 Department of Pathology, Xiangya Hospital, School of Basic Medical Sciences, Central South University, Changsha, China
- 2 Xiangya Medical School, Central South University, Changsha, China
- 3 Department of Neurology, The Third Xiangya Hospital of Central South University, Changsha, China
- 4 Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, China
- 5 China-Africa Research Center of Infectious Diseases, School of Basic Medical Sciences, Central South University, Changsha, China
- 6 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Received: August 2, 2023 Accepted: October 12, 2023 Published: January 23, 2024
https://doi.org/10.18632/aging.205225How to Cite
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.
Abbreviations
LAML: Acute myeloid leukemia; ACC: Adrenocortical carcinoma; BLCA: Bladder urothelial carcinoma; BSA: Bovine serum albumin; LGG: Brain lower grade glioma; BRCA: Breast invasive carcinoma; CCLE: Cancer cell line encyclopedia; cBioPortal: cBio cancer genomics portal; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; CRC: Colorectal cancer; Cis: Confidence intervals; CNV: Copy number variation; CTLs: Cytotoxic T lymphocytes; DSS: Disease specific survival; DMEM: Dulbecco’s modified eagle’s medium; EMT: Epithelial-mesenchymal transition; EC: Esophageal cancer; ESCA: Esophageal carcinoma; FDR: False discovery rate; FBS: Fetal bovine serum; GC: Gastric cancer; GO: Gene ontology; GSEA: Gene set enrichment analysis; GTEx: Genotype-tissue expression project; GBM: Glioblastoma multiforme; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GPCR: G-protein-coupled receptors; HR: Hazard ratios; HNSC: Head and neck squamous cell carcinoma; HPA: Human protein atlas; ICP: Immune checkpoint; IHC: Immunohistochemistry; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; KEGG: Kyoto encyclopedia of genes and genomes; LIHC: Liver hepatocellular carcinoma; lncRNA: Long non-coding RNA; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; DLBC: Lymphoid neoplasm diffuse Large B-cell lymphoma; MESO: Mesothelioma; NSCLC: Non-small cell lung cancers; NES: Normalized enrichment score; OSCC: Oral squamous cell carcinoma; OV: Ovarian serous cystadenocarcinoma; OS: Overall survival; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PFI: Progression-free interval; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; RT-qPCR: Reverse transcription-quantitative polymerase chain reaction; RPMI: Roswell park memorial institute; SARC: Sarcoma; ssGSEA: Single sample GSEA; SNVs: Single-nucleotide variants; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular germ cell tumors; TCGA: The cancer genome atlas; TCIA: The cancer immune atlas; THYM: Thymoma; THCA: Thyroid carcinoma; TIMER2: Tumor immune estimation resource version 2; TME: Tumor microenvironment; TILs: Tumor-infiltrating lymphocytes; UCS: Uterine carcinosarcoma; UCEC: Uterine corpus endometrial carcinoma; UVM: Uveal melanoma.