Prognostic role of HSPs in human colorectal cancer: a systematic review and meta-analysis

BACKGROUND: Heat shock proteins (HSPs) play pivotal roles in cellular stress responses and are associated with the progression and treatment resistance of various cancers. They are also critically important in the occurrence, development, and prognosis of colorectal cancer (CRC). However, the specific prognostic value of HSPs in CRC remains controversial. This study aimed to conduct a meta-analysis to evaluate the prognostic significance of HSPs in CRC patients. METHODS: Literature searches were conducted in the PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Biology Medicine (CBM) databases up to March 15, 2026. Data regarding the relationship between the expression of HSPs and survival outcomes were extracted. The pooled hazard ratio (HR) with a 95% confidence interval (CI) was calculated. RESULTS: We included 42 studies involving a total of 8,142 CRC patients. The results indicated that elevated levels of HSPs were associated with a poorer survival prognosis in CRC patients (HR = 1.78, 95% CI [1.48, 2.14]; p < 0.001). Subgroup analysis of overall survival revealed that high levels of HSP27 (HR = 1.72, 95% CI [1.23, 2.41]), HSP47 (HR = 2.43, 95% CI [1.82, 3.24]), HSP70 (HR = 2.14, 95% CI [1.74, 2.63]), and HSP90 (HR = 2.02, 95% CI [1.31, 3.14]) were significantly associated with a poorer survival prognosis in CRC patients(p < 0.05 for all comparisons). CONCLUSION: This meta-analysis highlights the significant role of HSPs in the prognostic evaluation of CRC patients. Elevated levels of HSP27, HSP47, HSP70, and HSP90 are identified as crucial biomarkers indicative of poor prognosis in CRC patients, with particularly noteworthy associations between high expression levels of HSP47 and HSP70 and adverse outcomes in CRC. While some heterogeneity was noted in the analysis, the results of the subgroup analysis reinforce the involvement of specific HSP family members in tumor progression. To further substantiate the independent prognostic value of HSPs and to investigate their potential as therapeutic targets for CRC, future studies should be rigorously designed, standardized, and conducted on a large scale.