Background: P4HB (prolyl 4-hydroxylase, beta polypeptide) is a human chromosomal gene that encodes an endoplasmic reticulum (ER) molecular chaperone protein with oxidoreductase, chaperone and isomerase activities. Recent studies indicated that P4HB may have clinical significance, with elevated P4HB expression reported in cancer patients, but its impact on tumor prognosis is not yet clear. To our knowledge, this is the first meta-analysis to show an association between P4HB expression and the prognosis of various cancers.
Methods: We conducted a systematic literature search in the PubMed, PubMed Central, Web of Science, Embase, CNKI, Wanfang and Weipu databases, followed by a quantitative meta-analysis using Stata SE14.0 and R statistics software 4.2.1. The hazard ratio (HR) and relative risk (RR) were analyzed to evaluate the relationships of P4HB expression levels with overall survival (OS), disease-free survival (DFS), and clinicopathological parameters of cancer patients. Subsequently, P4HB expression in various cancer types was validated using the Gene Expression Profiling Interactive Analysis (GEPIA) online database.
Results: Ten articles containing the data of 4121 cancer patients were included in the analysis, and a significant correlation of high P4HB expression with apparently shorter OS was found (HR, 1.90; 95% CI, 1.50-2.40; P < 0.01), while there was no significant correlation with gender (RR, 1.06; 95% CI, 0.91-1.22; P = 0.084), or age. Additionally, GEPIA online analysis revealed significant upregulation of P4HB in 13 types of cancer. Among them, P4HB overexpression was associated with shorter OS in 9 and worse DFS in 11 cancer types.
Conclusions: Upregulation of P4HB is correlated with worse prognosis in various cancers, which could provide new ideas for the development of P4HB-related diagnostic biomarkers and new therapeutic targets.
Keywords: Meta-analysis; P4HB; Prolyl 4-hydroxylase, beta polypeptide.
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