Abstract

Chemotherapy resistance is the main reason for the poor prognosis of ovarian cancer (OC). FHL1 is an important tumour regulator, but its relationship with the prognosis, drug resistance, and tumour microenvironment of OC is unknown. Immunohistochemistry was used to determine FHL1 expression in OC. Kaplan‒Meier plotter was used for survival analysis. The value of gene expression in predicting drug resistance was estimated using the area under the curve (AUC). Bivariate correlation was used to determine the coexpression of two genes. Functional cluster and pathway enrichment were used to uncover hidden signalling pathways. The relationship between gene levels and the tumour microenvironment was visualised through the ggstatsplot and pheatmap packages. The mRNA and protein levels of FHL1 were downregulated in 426 and 100 OC tissues, respectively. Low FHL1 expression was correlated with good progression-free survival (PFS), postprogression survival, and overall survival (OS) in 1815 OC patients, and was further confirmed to be associated with good OS by immunohistochemistry in 152 OC tissues. Furthermore, FHL1 was downregulated in drug-sensitive tissues, while its high expression predicted drug resistance (AUC > 0.65). Mechanistically, FHL1 was coexpressed with FLNC, CAV1, PPP1R12B, and FLNA at the mRNA and protein levels in 558 and 174 OC tissues, respectively, and their expression was downregulated in OC. Additionally, very strong coexpression of FHL1 with the four genes was identified in at least 23 different tumours. Low expression of the four genes was associated with good PFS, and the combination of FHL1 with the four genes provided better prognostic power. Meanwhile, the expression of all five genes was strongly and positively associated with the abundance of macrophages. Low FHL1 expression acts as a favourable factor in OC, probably via positive coexpression with FLNC, CAV1, PPP1R12B, and FLNA.

中文翻译：

---

FHL1低表达表明卵巢癌预后良好且药物敏感性良好

摘要

化疗耐药是卵巢癌（OC）预后不良的主要原因。FHL1是重要的肿瘤调节因子，但其与OC的预后、耐药性和肿瘤微环境的关系尚不清楚。免疫组织化学用于测定 OC 中 FHL1 的表达。Kaplan-Meier 绘图仪用于生存分析。使用曲线下面积（AUC）估计基因表达在预测耐药性中的价值。使用双变量相关性来确定两个基因的共表达。功能簇和通路富集用于揭示隐藏的信号通路。通过 ggstatsplot 和 pheatmap 软件包可视化基因水平与肿瘤微环境之间的关系。FHL1 mRNA 和蛋白水平分别在 426 例和 100 例 OC 组织中下调。在 1815 名 OC 患者中，低 FHL1 表达与良好的无进展生存期 (PFS)、进展后生存期和总生存期 (OS) 相关，并且在 152 名 OC 组织中通过免疫组织化学进一步证实其与良好的 OS 相关。此外，FHL1在药物敏感组织中下调，而其高表达预示着耐药性（AUC > 0.65）。从机制上讲，在 558 例和 174 例 OC 组织中，FHL1 分别在 mRNA 和蛋白水平上与 FLNC、CAV1、PPP1R12B 和 FLNA 共表达，并且它们的表达在 OC 中下调。此外，在至少 23 种不同的肿瘤中发现了 FHL1 与这四种基因的非常强的共表达。这四个基因的低表达与良好的 PFS 相关，FHL1 与这四个基因的组合提供了更好的预后能力。同时，所有五个基因的表达与巨噬细胞的丰度呈强烈正相关。FHL1 低表达是 OC 中的有利因素，可能是通过与 FLNC、CAV1、PPP1R12B 和 FLNA 的正共表达实现的。