FOXJ1 蛋白表达增加与高级别浆液性卵巢癌患者总生存期的改善相关：卵巢肿瘤组织分析联盟研究。

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

机构信息

School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, NSW, Australia.

Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia.

出版信息

Br J Cancer. 2023 Jan;128(1):137-147. doi: 10.1038/s41416-022-02014-y. Epub 2022 Nov 2.

DOI:10.1038/s41416-022-02014-y

PMID:36323878

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9814937/

Abstract

BACKGROUND

Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

METHODS

Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.

RESULTS

Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant.

CONCLUSION

We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

摘要

背景

最近，我们发现，在基于 101 个基因 mRNA 表达预后标志物的分层中，患有输卵管-卵巢高级别浆液性癌（HGSC）的患者在 5 年生存率上存在 >60%的差异。鉴于患者预后的多样性，本研究旨在通过免疫组织化学将预后 mRNA 标志物转化为蛋白表达检测，并验证其在 HGSC 中的生存相关性。

方法

根据高质量抗体、与蛋白表达的相关性以及初步队列中免疫组织化学评分的变化，选择了两个预后基因 FOXJ1 和 GMNN（分别为 n = 134 和 n = 80）。在组织微阵列上，有 6434 例（FOXJ1）和 5470 例（GMNN）福尔马林固定、石蜡包埋的卵巢肿瘤（分别为 4634 例和 4185 例 HGSC）接受了免疫组织化学染色和评分，然后进行了单变量和多变量生存分析。

结果

与 mRNA 一致，FOXJ1 蛋白表达与 HGSC 患者的总生存呈线性增加相关。表达 >50%的女性具有最佳结局（HR = 0.78，95%CI 0.67-0.91，p < 0.0001）。GMNN 蛋白表达与 HGSC 患者的总生存无显著相关性。然而，GMNN 表达 >35%的 HGSC 显示出更好结局的趋势，但无统计学意义。