成纤维细胞激活蛋白（FAP）高表达预示高级别浆液性卵巢癌预后不良。

High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer.

机构信息

Department of Gynecology & Obstetrics, the First Affiliated Hospital of Soochow University, No.188, Shizi Street, Suzhou, Jiangsu Province, 215006, China.

Department of Pathology, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.

出版信息

BMC Cancer. 2020 Oct 27;20(1):1032. doi: 10.1186/s12885-020-07541-6.

BACKGROUND

High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC.

METHODS

TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC.

RESULTS

Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival.

CONCLUSIONS

High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

背景

高级别浆液性卵巢癌（HGSOC）是一种致命的卵巢癌形式。先前的研究表明，一些潜在的生物标志物可用于 HGSOC 预后的临床评估。然而，缺乏对差异表达基因（DEGs）的系统分析，以筛选和检测 HGSOC 的显著生物标志物。

方法

利用 TCGA 数据库分析 HGSOC 相关基因的表达。通过 Cox 回归分析计算候选基因表达的结局，包括总生存期（OS）和无进展生存期（PFS），以计算危险比（HR）。对 151 例中国 HGSOC 患者进行了鉴定基因的组织病理学研究，以验证不同分期 HGSOC 中基因的表达情况。

结果

在分析的所有 57331 个基因中，FAP 被确定为唯一显著影响 HGSOC OS 和 PFS 的新基因。此外，FAP 在 HGSOC 的癌旁组织和早期晚期阶段具有一致的表达谱。石蜡切片的免疫组化检测也证实了 FAP 在晚期 HGSOC 患者中的上调表达。对 FAP 网络关联的预测表明，FN1 可能是影响 HGSOC 生存的潜在下游基因。