Abstract
Platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) plays a critical role in cancer initiation, metastasis, and progression; however, it remains unknown how PAFAH1B3 impacts cancer diagnosis and prognosis or regulates the immune response to different types of cancer. In this study, PAFAH1B3 was elevated in human pan-cancer, and this correlated with greater pathology and poor prognosis, in particular for non-small cell lung cancer (NSCLC) and liver hepatocellular carcinoma (LIHC). In addition, PAFAH1B3 expression was positively associated with tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, immune-modulatory related gene expression, and diverse cancer drug sensitivity in human cancer. Increased PAFAH1B3 expression correlated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of NSCLC and LIHC, and has potential as an independent risk factor for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) during LIHC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis confirmed that PAFAH1B3 is primarily involved in immune regulation. More importantly, results demonstrated that PAFAH1B3 was upregulated in liver cancer cells lines and that knockdown of this gene significantly inhibited cell proliferation, migration, and invasion in liver hepatocellular carcinoma (LIHC). In summary, this study elucidates the clinical significance and biological function of PAFAH1B3 during liver hepatocellular carcinoma (LIHC) and may serve as a potential biomarker for the diagnosis and prognosis of various cancer types.
Highlights
Cancer affects millions of people each year and poses a substantial societal and economic burden worldwide
PAFAH1B3 expression was higher in adenoid cystic carcinoma (ACC), bladder urothelial carcinoma (BLCA), breast cancer (BRCA), cervical squamous cell carcinoma (CESC), colon adenocarcinoma (COAD), CHOL, diffuse large B-cell lymphoma (DLBCL), esophageal carcinoma (ESCA), glioblastoma (GBM), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), low-grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), ovarian cancer (OV), pancreatic adenocarcinoma (PAAD), prostrate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD), tenosynovial giant cell tumor (TGCT), thyroid cancer (THCA), thymus cancer (THYM), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS) (Figure 1B)
PAFAH1B3 was significantly elevated in breast cancer, colon cancer, ovarian cancer, clear cell renal cell carcinoma (RCC), and UCEC (Figure 1D)
Summary
Cancer affects millions of people each year and poses a substantial societal and economic burden worldwide. There is an urgent need to identify specific molecular targets to improve cancer diagnosis and treatment. Michael et al showed that PAFAH1B3 may be a potential target for tyrosine kinase inhibitors (TKIs) in breast cancer (BRCA) (Fiedler et al, 2018). Lissencephaly associated mutations will destroy the interaction between PAFAH1B3 and PAFAH1B2, leading to inhibitions in the neuronal migration (Xing et al, 2011). These studies indicate that PAFAH1B3 regulates diverse biological functions in cancer initiation, metastasis, and progression, and may be a promising prognostic and therapeutic biomarker for pan-cancer. The specific role of PAFAH1B3 in diagnosis, prognosis, and immune regulation in various types of cancer remains unexplored
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