Wang Feiyang, Yu Zhixiang, Liu Xiaohan, Hu Feng, Liu Xiangjun, Fu Xinyi, Liu Yan, Zou Zhenhong
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China; The First School of Clinical Medicine of Nanchang University, Jiangxi Medical College of Nanchang University, No.461 Bayi Avenue, Nanchang 330000, Jiangxi, People's Republic of China.
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang 330006, Jiangxi, People's Republic of China.
Pathol Res Pract. 2023 May;245:154474. doi: 10.1016/j.prp.2023.154474. Epub 2023 Apr 20.
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.
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.
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.
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.
P4HB（脯氨酰4-羟化酶，β多肽）是一种人类染色体基因，编码一种具有氧化还原酶、伴侣蛋白和异构酶活性的内质网（ER）分子伴侣蛋白。最近的研究表明，P4HB可能具有临床意义，癌症患者中P4HB表达升高，但它对肿瘤预后的影响尚不清楚。据我们所知，这是第一项显示P4HB表达与各种癌症预后之间存在关联的荟萃分析。
我们在PubMed、PubMed Central、Web of Science、Embase、CNKI、万方和维普数据库中进行了系统的文献检索，随后使用Stata SE14.0和R统计软件4.2.1进行定量荟萃分析。分析风险比（HR）和相对风险（RR），以评估P4HB表达水平与癌症患者总生存期（OS）、无病生存期（DFS）和临床病理参数之间的关系。随后，使用基因表达谱交互式分析（GEPIA）在线数据库验证各种癌症类型中P4HB的表达。
分析纳入了10篇包含4121例癌症患者数据的文章，发现P4HB高表达与明显较短的OS显著相关（HR，1.90；95%CI，1.50 - 2.40；P < 0.01），而与性别（RR，1.06；95%CI，0.91 - 1.22；P = 0.084）或年龄无显著相关性。此外，GEPIA在线分析显示13种癌症中P4HB显著上调。其中，P4HB过表达与9种癌症的较短OS和11种癌症的较差DFS相关。
P4HB上调与各种癌症的较差预后相关，这可为开发与P4HB相关的诊断生物标志物和新的治疗靶点提供新思路。
