Research Paper Volume 15, Issue 14 pp 7056—7083
Identifying the oncogenic roles of FAP in human cancers based on systematic analysis
- 1 School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China
- 2 Department of Vascular Surgery, Weifang Yidu Central Hospital, Weifang 262500, Shandong, China
Received: January 16, 2023 Accepted: June 22, 2023 Published: July 24, 2023
https://doi.org/10.18632/aging.204892How to Cite
Copyright: © 2023 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Fibroblast activation protein-α (FAP) is a specific marker of cancer-associated fibroblasts (CAFs) and plays a crucial role in tumor development. However, the biological processes underlying FAP expression in tumor progression and tumor immunity have not been fully elucidated.
Methods: We utilized RNA-seq data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to perform differential analysis of FAP expression in tumor tissues and matched-normal tissues. The relationship between FAP expression and clinical prognosis, DNA methylation, and tumor-infiltrating immune cells in pan-cancer was assessed using R Studio (version 4.2.1). Additionally, we employed gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to investigate the biological functions and pathways associated with FAP expression.
Results: FAP exhibits high expression in most malignancies, albeit to a lesser extent in CESC, KICH, UCEC, SKCM, THCA, and UCS. Furthermore, FAP is either positively or negatively associated with the prognosis of several malignancies. In seven types of cancer, FAP expression is positively correlated with DNA methylation. CIBERSORT analysis revealed an inverse correlation between FAP expression and T cells, B cells, monocytes, and NK cells, while it exhibited a positive correlation with M0, M1, and M2 macrophages. Enrichment analysis further demonstrated that FAP modulates the cell cycle, epithelial-mesenchymal transition (EMT) process, angiogenesis, and immune-related functions and pathways.
Conclusion: Our findings indicate a close relationship between FAP expression and tumorigenesis as well as tumor immunity. FAP has the potential to serve as a diagnostic, prognostic, and immunotherapy marker.
Abbreviations
ACC: Adrenocortical carcinoma; AUC: Area under the curve; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CAFs: Cancer-associated fibroblasts; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; CCLE: Cancer cell line encyclopedia; COAD: Colon adenocarcinoma; COADREAD: Colon adenocarcinoma/Rectum adenocarcinoma esophageal carcinoma; DSS: Disease-specific survival; DFI: Disease-free interval; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: Esophageal carcinoma; FAP: Fibroblast activation protein-α; GTEx: Genotype Tissue-Expression; GSEA: Gene set enrichment analysis; GSVA: Gene set variation analysis; GBM: Glioblastoma multiforme; GBMLGG: Glioma; HNSC: Head and Neck squamous cell carcinoma; ICIs: Immune checkpoint inhibitors; KICH: Kidney chromophobe; KM: Kaplan-Meier; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Brain lower grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; NCI: National Cancer Institute; OS: Overall survival; OV: Ovarian serous cystadenocarcinoma; PFI: Progress-free interval; PPI: Protein-protein interaction; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; ROC: Receiver operating characteristic curve; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; STES: Stomach and esophageal carcinoma; TCGA: The Cancer Genome Atlas; TIICs: Tumor-infiltrating immune cells; TME: Tumor microenvironment; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma.