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

Fei Chen,Pengxiu Cao,Bo Zhang,Yumei Fan,Bing Liu,Jiajie Hou,Ke Tan,Yusuf Tutar

doi:10.1155/2021/5551036

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.

Highlights

Cancer is a leading cause of morbidity and mortality worldwide, and it imposes a major health and economic burden on society [1]
The heat shock factor 1 (HSF1) expression was significantly higher in cancer versus adjacent normal tissues in the bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), CHOL, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and thyroid carcinoma (THCA) datasets (Figure 1(a))
Among 38 subtypes of immune cells, we found that the HSF1 expression negatively and significantly correlated with these subtypes in LUAD, LUSC, SARC, skin cutaneous melanoma (SKCM), STAD, THCA, and uterine corpus endometrial carcinoma (UCEC) (Figure 8(b))

Summary

Introduction

Cancer is a leading cause of morbidity and mortality worldwide, and it imposes a major health and economic burden on society [1]. Cancer treatment strategies primarily include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy [1]. These therapies exhibit some clinical success, the prognosis and survival rate of patients remain unsatisfactory due to drug resistance, side effects, and other problems [2]. The lack of nutrients and oxygen, ATP depletion, and the inflammatory response in the tumor microenvironment (TME) creates a long-term stressful living environment for tumor cells [6, 7] This stress signaling leads to the activation of heat shock factor 1 (HSF1), which induces unique transcriptional programs to address these alterations [8,9,10]. Consistent with these observations, a growing number of studies showed that HSF1 was overexpressed and/or activated in various types of cancer and negatively associated with the prognosis of cancer patients [8,9,10]

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Results

Discussion

Conclusion