HSF4 as a Prognostic Predictor and Therapeutic Target in Colorectal Cancer Linked to Immune Status

Colorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The Heat Shock Factor (HSF) family of genes plays a pivotal role in the cellular response to environmental stress, particularly heat stress. These genes encode transcription factors that regulate the expression of heat shock proteins, which are crucial for maintaining cellular homeostasis under stressful conditions. Recently, there has been increasing interest in the role of HSF family genes in the development and progression of CRC. In this study, we conducted a comprehensive analysis of CRC samples from The Cancer Genome Atlas (TCGA) database to identify potential therapeutic targets. A total of 533 samples’ gene expression matrices, including 42 normal and 491 tumor samples, were downloaded and processed. Differential expression analysis of the HSF family genes was performed, revealing HSF4 as the most significantly differentially expressed gene between normal and tumor samples. So the HSF4-related signature was constructed, and all CRC patients in TCGA dataset were stratified as low-risk or high-risk groups according to HSF4’s expression. Survival analysis demonstrated a significant association between HSF4 expression and clinical outcomes that means the signature had a powerful prognostic value. Correlation analysis further revealed significant relationships between HSF4 expression and clinical features such as Stage, T stage, M stage, and N stage. Univariate and multivariate Cox regression analysis confirmed the prognostic significance of HSF4. Functional analysis of differentially expressed genes based on HSF4 expression levels revealed enrichment in critical biological processes and pathways. Additionally, it has unique properties in tumor microenvironment (TME). Further analysis showed that different risk groups have different immune cell infiltration and cell proliferation ability. Finally, the low-risk group was sensitive to multiple chemotherapeutic drugs because of its lower IC50. In conclusion, this is the first signature to predict the prognosis and immunological status of CRC patients based on HSF family genes. Our findings suggest that HSF4 may serve as a potential therapeutic target in CRC.