Research Paper Advance Articles
Pro-apoptotic gene BAX is a pan-cancer predictive biomarker for prognosis and immunotherapy efficacy
- 1 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu, P.R. China
- 2 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225012, Jiangsu, P.R. China
Received: August 30, 2023 Accepted: June 10, 2024 Published: July 5, 2024
https://doi.org/10.18632/aging.206003How to Cite
Copyright: © 2024 Wang 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: Apoptosis Regulator BCL2 Associated X (BAX) is a pro-apoptotic gene. Apoptosis is one of the important components of immune response and immune regulation. However, there is no systematic pan-cancer analysis of BAX.
Methods: Original data of this study were downloaded from TCGA databases and GTEX databases. We conducted the gene expression analysis and survival analysis of BAX in 33 types of cancer via Gene Expression Profiling Interactive Analysis (GEPIA) database. Real-time PCR and immunohistochemistry (IHC) were further performed to examine the BAX expression in cancer cells and tissues. Moreover, the relationship between BAX and immune infiltration and gene alteration was studied by the Tumor Immune Estimation Resource (TIMER) and cBioPortal tools. Protein–protein interaction analysis was performed in the STRING database. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to evaluate the enrichment analysis.
Results: BAX was highly expressed in most cancers and was associated with poor prognosis in nine cancer types. In addition, BAX showed significant clinical relevance, and the mRNA expression of BAX was also strongly associated with drug sensitivity of many drugs. Furthermore, BAX may participate in proliferation and metastasis of many cancers and was associated with methylation. Importantly, BAX expression was positively correlated with most immune infiltrating cells.
Conclusion: Our findings suggested that BAX can function as an oncogene and may be used as a potential predictive biomarker for prognosis and immunotherapy efficacy of human cancer, which could provide a new approach for cancer therapy.
Abbreviations
BAX: BCL2 Associated X; GEPIA: Gene Expression Profiling Interactive Analysis; IHC: Immunohistochemistry; CNV: Copy-number variation; TIMER: Tumor Immune Estimation Resource; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TCGA: The Cancer Genome Atlas; HPA: Human Protein Atlas database; OS: Overall survival; DFS: Disease-free survival; GSCA: Gene Set Cancer Analysis; TILs: Tumor-infiltrating lymphocytes; EMT: Epithelial–mesenchymal transition; PPI: Protein-protein interaction; STRING: Search tool for the retrieval of interacting genes; RT-qPCR: Real time quantitative polymerase chain reaction; CPTCA: Clinical Proteomic Tumor Analysis Consortium; ESAC: Esophageal carcinoma; LIHC: Liver hepatocellular carcinoma; LGG: Brain lower grade glioma; GBM: Glioblastoma multiforme; ACC: Adrenocortical carcinoma; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; BRCA: Breast invasive carcinoma; BLCA: Bladder urothelial carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; HNSC: Head and Neck squamous cell carcinoma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; LUSC: Lung squamous cell carcinoma; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; THCA: Thyroid carcinoma; TGCT: Testicular germ cell tumors; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; nTPM: Normalized protein-coding transcripts per million; AUC: Area under the curve; GDSC: Genomics of Drug Sensitivity in Cancer; CTRP: Cancer Therapeutics Response Portal; CDH2: N-cadherin; TWIST1: Twist Family BHLH Transcription Factor 1; MKI6: Marker of Proliferation Ki-67; PCNA: Proliferating Cell Nuclear Antigen; TP53: Tumor Protein P53; MDM2: MDM2 Proto-Oncogene; AKT1: AKT Serine/Threonine Kinase 1; ATM: ATM Serine/Threonine Kinase; PRPF31: Pre-MRNA Processing Factor 31; BBC3: BCL2 Binding Component 3, R = 0.5; PIH1D1: PIH1 Domain Containing 1; LIG1: DNA Ligase 1; PRMT1: Protein Arginine Methyltransferase 1; CC: Cellular component; BP: Biological process; MF: Molecular function; ESAC: Esophageal carcinoma; MPS I: Mucopolysaccharidosis type I.