HSF4: A Prognostic Predictor and Potential Therapeutic Target in Colorectal Cancer with Implications for Patient Immune Status

Colorectal cancer (CRC) is among the most prevalent malignancies globally, characterized by high morbidity and mortality rates. The Heat Shock Factor (HSF) family of genes plays a critical 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 essential for maintaining cellular homeostasis under stressful conditions. Recently, there has been a growing 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 gene expression matrices, were downloaded and processed, including 42 normal and 491 tumor samples. Differential expression analysis of the HSF family genes, revealed HSF4 as the most significantly differentially expressed gene between normal and tumor samples. Consequently an HSF4-related signature was constructed, stratifying all CRC patients in the TCGA dataset into low-risk or high-risk groups based on HSF4 expression. Survival analysis demonstrated a significant association between HSF4 expression and clinical outcomes indicating that the signature possesses substantial. Correlation analysis further revealed significant relationships between HSF4 expression and clinical features including Stage, T stage, M stage, and N stage. Univariate and multivariate Cox regression analyses confirmed the prognostic significance of HSF4. Functional analysis of differentially expressed genes based on HSF4 expression levels demonstrated enrichment in critical biological processes and pathways. Furthermore, HSF4 exhibited unique properties within the tumor microenvironment (TME). Additional analysis indicated that different risk groups exhibit varying levels of immune cell infiltration and cell proliferation capacity. Notably, the low-risk group showed increased sensitivity to multiple chemotherapeutic agents due to its lower IC50 values. In conclusion, this study presents the first signature for predicting 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.