Pan‐Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy

Abstract

Emerging evidence revealed the significant roles of heat shock factor 1 (HSF1) in cancer initiation, development, and progression, but there is no pan-cancer analysis of HSF1. The present study first comprehensively investigated the expression profiles and prognostic significance of HSF1 and the relationship of HSF1 with clinicopathological parameters and immune cell infiltration using bioinformatic techniques. HSF1 is significantly upregulated in various common cancers, and it is associated with prognosis. Pan-cancer Cox regression analysis indicated that the high expression of HSF1 was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), and kidney renal papillary cell carcinoma (KIRP) patients. The methylation of HSF1 DNA was decreased in most cancers and negatively correlated with the HSF1 expression. Increased phosphorylation of S303, S307, and S363 in HSF1 was observed in some cancers. HSF1 remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. Our pan-cancer analysis provides a deep understanding of the functions of HSF1 in oncogenesis and metastasis in different cancers.

Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

“…Notably, our GSEA and KEGG results suggested that HSF2 was also involved in many immunity-associated pathways (IL−17 signaling pathway and the adaptive immune system) and various microbial infections (hepatitis B, shigellosis, Yersinia infection, and herpes simplex virus 1 infection) (Figures 5,6). A recently study showed that HSF2 was upregulated in ulcerative colitis and was negatively associated with colon inflammation in mice (Wang W. et al, 2020;Zhang F. et al, 2021). NLRP3 inflammasome activation and IL-1β secretion are greatly enhanced in HSF2−/− DSS model mice (Zhang et al, 2020).…”

“…More importantly, serum HSF2 levels are positively correlated with the expression of IL-1β and TNF-α. Knockdown of HSF2 potentiates the production of IL-1β and TNF-α induced by LPS (Miao et al, 2014;Wang W. et al, 2020;Zhang et al, 2020;Santopolo et al, 2021;Zhang F. et al, 2021). Here, to further estimate the relationships between HSF2 and the TME, we first examined the correlation of HSF2 expression and the abundance of different infiltrating immune cells across different cancer types.…”

“…Numerous studies have demonstrated that HSF1 is associated with DNA damage repair, reprogrammed metabolism oncogenesis, and metastasis ( Mendillo et al, 2012 ; Dai and Sampson, 2016 ; Dai, 2018 ; Wang G. et al, 2020 ; Puustinen and Sistonen, 2020 ). Thus, HSF1 is believed to be a potential therapeutic target for anticancer therapy ( Zhang B. et al, 2021 ; Chen et al, 2021 ).…”

Integrated Bioinformatics Analysis Identifies Heat Shock Factor 2 as a Prognostic Biomarker Associated With Immune Cell Infiltration in Hepatocellular Carcinoma

“…GSEA was used to investigate the potential mechanisms of hepcidin. The GO, KEGG and GSEA results were explored using the R package ClusterProfiler ( Chen et al, 2021 ).…”

“…Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis GO analysis, KEGG analysis and GSEA were applied to investigate the biological functions and potential mechanisms of HSF2 in HCC. GO analysis is a powerful bioinformatics method that annotates and categorizes genes according to biological processes (BPs), cellular components (CCs) and molecular functions (MFs) (Chen et al, 2021). GSEA was used to investigate the potential mechanisms of hepcidin.…”