CD31在前列腺癌中的分子功能及临床意义

Molecular function and clinical significance of CD31 in prostate adenocarcinoma

目的探索前列腺癌中血小板内皮细胞黏附分子(CD31)的分子功能及对患者预后的影响,明确穿刺标本中CD31-微血管密度值(microvessel density,MVD)对前列腺癌的预测价值。方法从肿瘤基因组图谱(the cancer genome atlas,TCGA)数据库获取前列腺癌测序数据,通过基因集变异分析(GSVA)探索CD31在前列腺癌中的分子功能,通过KM曲线分析明确CD31的预后价值。收集在郴州市第一人民医院行膀胱癌根治术、经尿道前列腺切除术及前列腺癌根治术的组织标本,分别获取正常前列腺组织,前列腺增生组织,癌旁组织及前列腺癌组织4类组织标本,通过免疫组化检测CD31的表达并测算MVD值,明确在以上组织中CD31-MVD表达是否存在差异。收集首次前列腺穿刺为阴性的前列腺癌患者的标本,检测穿刺组织中的CD31-MVD,通过logistic回归模型明确CD31-MVD与前列腺癌的相关性,通过ROC曲线对其预测效能进行评估。结果通过对492例前列腺癌中CD31的基因集变异分析,结果显示CD31与血管生成相关的生物学过程呈正相关,在CD31高表达组中,血管生成、重构及形态变化,血管上皮细胞分化和迁移,VEGF通路调控都显著富集(P<0.05)。KM曲线结果显示CD31高表达组前列腺癌患者无病生存期(DFS)显著降低(P=0.0095,HR=1.7)。CD31-MVD在前列腺癌组织中最高,较正常前列腺组织及前列腺增生组织增高(P<0.05);癌旁组织与前列腺癌组织的CD31-MVD比较差异无统计学意义(P>0.05)。Logistic回归模型表明穿刺标本中CD31-MVD与前列腺癌显著相关(P<0.05,OR=1.138,95%CI:1.019~1.308)。ROC曲线分析显示在CD31-MVD为14.7时,特异性为66.7%,灵敏度为81.8%,ROC曲线下方面积(AUC)为0.755,对于前列腺癌具有最佳预测价值。结论CD31可能促进前列腺癌侵袭及血管生成,是前列腺癌患者预后不良的独立危险因素,前列腺穿刺组织中CD31-MVD对前列腺癌有预测价值。

Objective To explore the molecular function of CD31 in prostate adenocarcinoma(PRAD)and its influence on patient prognosis,and to clarify the predictive value of the CD31-microvessel density(MVD)in biopsy specimens for PRAD.Methods RNA-seq data of PRAD was obtained from The Cancer Genome Atlas(TCGA)dataset.The molecular function of CD31 in prostate adenocarcinoma was explored by gene set variation analysis(GSVA)and the prognostic value of CD31 was determined by KM curve analysis.Tissue specimens from patients who respectively received radical cystectomy,trans urethral resection prostate and radical prostatectomy were collected in Chenzhou No.1 People’s Hospital.This 4 kinds of tissue samples including the normal prostate tissue,hyperplasia of prostate tissue,the tissue adjacent to PRAD and PRAD tissues were obtained respectively.The expression of CD31 was detected by immunohistochemistry analysis and the MVD value was measured to determine whether there were differences in CD31-MVD in the above tissues.Samples were collected from patients with prostate cancer whose first prostate biopsy was negative,and CD31-MVD was detected in the puncture tissue.The correlation between CD31-MVD and prostate cancer was determined by logistic regression model,and its predictive efficacy was evaluated by ROC curve.Results analyzing the variation of CD31 gene set in 492 cases of PRAD,the results showed that CD31 was positively correlated with the biological processes related to angiogenesis.In the CD31 high expression group,angiogenesis,remodeling and morphological changes,vascular epithelial cell differentiation and migration,and VEGF pathway regulation were significantly enriched(P<0.05).KM curve results showed that the disease-free survival(DFS)of prostate cancer patients with high CD31 expression was significantly reduced(P=0.0095,HR=1.7).The CD31-MVD in PRAD was the highest,higher than that in normal and prostate hyperplasia tissues(P<0.05),but there was no significant difference between CD31-MVD in PRAD and adjacent tissues(P>0.05).Logistic regression model showed that CD31-MVD was significantly correlated with PRAD in prostate needle biopsy specimens(P<0.05,OR=1.138,95%CI:1.019^-1.308).ROC curve analysis showed that when CD31-MVD was 14.7,the specificity was 66.7%,the sensitivity was 81.8%,and the area under the ROC curve(AUC)was 0.755,which had the best predictive value for PRAD.Conclusion CD31 might promote the aggressiveness and angiogenesis in PRAD,and it is an independent risk factor for poor prognosis of PRAD patients.CD31-MVD in prostate needle biopsy specimens has predictive value for PRAD.