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聚合免疫球蛋白受体在上皮性卵巢癌中的表达及预后意义

Expression and prognostic significance of the polymeric immunoglobulin receptor in epithelial ovarian cancer.

作者信息

Berntsson Jonna, Lundgren Sebastian, Nodin Björn, Uhlén Mathias, Gaber Alexander, Jirström Karin

机构信息

Department of Clinical Sciences, Division of Pathology, Lund University, 221 85 Lund, Sweden.

出版信息

J Ovarian Res. 2014 Feb 26;7:26. doi: 10.1186/1757-2215-7-26.

Abstract

BACKGROUND

High expression of the polymeric immunoglobulin receptor (PIGR) has previously been associated with a favourable prognosis in a few cancer forms, but its expression and relationship with clinical outcome in epithelial ovarian cancer (EOC) has not yet been reported. The aim of this study was therefore to examine the clinicopathological correlates and prognostic significance of PIGR expression in EOC.

METHODS

After an initial screening in the Human Protein Atlas portal, a validated antibody was selected for extended analysis of immunohistochemical PIGR expression in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian tubes (n = 38) and omental metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were applied to examine the impact of PIGR expression on overall survival (OS) and ovarian cancer-specific survival (OCSS).

RESULTS

PIGR expression was significantly higher in fallopian tubes compared to primary tumours and metastases (p < 0.001) and lower in carcinoma of the serous subtype compared to other carcinomas (p < 0.001). PIGR expression was significantly associated with lower grade (p = 0.001), mucinous histological subtype (p = 0.002), positive progesterone receptor expression (p = 0.009) and negative or low Ki-67 expression (p = 0.003). Kaplan-Meier analysis revealed a significantly improved OS (p = 0.013) and OCSS (p = 0.009) for patients with tumours displaying high expression of PIGR. These associations were confirmed in unadjusted Cox regression analysis (HR = 0.48; 95% CI 0.26-0.87; p = 0.015 for OS and HR = 0.43, 95% CI 0.22-0.82; p = 0.011 for OCSS) but did not remain significant after adjustment for age, grade and clinical stage.

CONCLUSIONS

This study provides a first demonstration of PIGR expression in human fallopian tubes, primary EOC tumours and metastases. High tumour-specific expression of PIGR was found to be associated with a favourable prognosis in unadjusted, but not in adjusted, analysis. These findings are novel and merit further investigation.

摘要

背景

此前,聚合免疫球蛋白受体(PIGR)的高表达与少数几种癌症的良好预后相关,但尚未有其在上皮性卵巢癌(EOC)中的表达情况及其与临床结局关系的报道。因此,本研究旨在探讨EOC中PIGR表达的临床病理相关性及预后意义。

方法

在人类蛋白质图谱数据库进行初步筛选后,选择一种经过验证的抗体,对来自两个基于人群的前瞻性队列的154例EOC新发病例肿瘤组织芯片中的PIGR免疫组化表达进行深入分析。还分析了相应的外观正常的输卵管(n = 38)和网膜转移灶(n = 33)的子集。采用Kaplan-Meier分析和Cox回归分析,以检验PIGR表达对总生存期(OS)和卵巢癌特异性生存期(OCSS)的影响。

结果

与原发性肿瘤和转移灶相比,输卵管中的PIGR表达显著更高(p < 0.001);与其他类型的癌相比,浆液性亚型癌中的PIGR表达更低(p < 0.001)。PIGR表达与低级别(p = 0.001)、黏液性组织学亚型(p = 0.002)、孕激素受体阳性表达(p = 0.009)以及Ki-67阴性或低表达(p = 0.003)显著相关。Kaplan-Meier分析显示,PIGR高表达的肿瘤患者的OS(p = 0.013)和OCSS(p = 0.009)显著改善。这些关联在未校正的Cox回归分析中得到证实(OS的HR = 0.48;95%CI 0.26 - 0.87;p = 0.015;OCSS的HR = 0.43,95%CI 0.22 - 0.82;p = 0.011),但在对年龄、级别和临床分期进行校正后不再显著。

结论

本研究首次展示了PIGR在人输卵管、原发性EOC肿瘤及转移灶中的表达情况。在未校正分析中,发现PIGR的高肿瘤特异性表达与良好预后相关,但在校正分析中并非如此。这些发现具有创新性,值得进一步研究。

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