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Hsp90 是卵巢癌预后的潜在风险因素:来自中国临床中心的证据。

Hsp90 is a potential risk factor for ovarian cancer prognosis: an evidence of a Chinese clinical center.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, 218Th Jixi Road, Hefei, 230022, P.R. China.

NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China.

出版信息

BMC Cancer. 2023 May 31;23(1):489. doi: 10.1186/s12885-023-10929-9.

Abstract

BACKGROUND

The potential treatment effects of heat shock protein 90 (Hsp90) inhibitors in ovarian cancer (OC) are controversial. This research aims to investigate the relationship between the level of Hsp90 in peripheral blood and the prognosis of OC patients, as well as the clinicopathological indicators.

MATERIALS AND METHODS

We retrospectively collected the clinicopathological indicators of OC patients who were admitted to the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Anhui Medical University from 2017 to 2022. Hsp90 level in patient blood was detected by enzyme-linked immunosorbent assay, and the correlation between Hsp90 level and OC prognosis was systematically investigated. Kaplan-Meier method was used to draw the survival curve, and the average survival time and survival rate were calculated. The log-rank test and Cox model were used for univariate survival analysis, and the Cox proportional hazards model was applied for multivariate survival analysis. Based on the TCGA dataset of OC obtained by cBioPortal, Pearson's correlation coefficients between Hsp90 level values and other mRNA expression values were calculated to further conduct bioinformatics analysis. GSEA and GSVA analysis were also conducted for gene functional enrichment. The expression of Hsp90 in OC tissues were evaluated and compared by Immunohistochemical staining.

RESULTS

According to the established screening criteria, 106 patients were selected. The enzyme-linked immunosorbent assay results showed that 50.94% OC patients with abnormal Hsp90 level. According to the outcome of Kaplan-Meier curves, the results revealed that the abnormal level of Hsp90 was suggested to poor prognosis (P = 0.001) of OC patients. Furthermore, the result of multivariate Cox proportional hazards regression model analysis also predicted that abnormal Hsp90 level (HR = 2.838, 95%CI = 1.139-7.069, P = 0.025) was linked to poor prognosis, which could be an independent prognostic factor for the prognosis of OC patients. Moreover, top 100 genes screened by Pearson's value associated with Hsp90, indicating that Hsp90 participated in the regulation of ATF5 target genes, PRAGC1A target genes and BANP target genes and also enriched in the metabolic processes of cell response to DNA damage stimulus, response to heat and protein folding.

CONCLUSION

Hsp90 level is positively associated with OC mortality and is a potential prognostic indicator of OC.

摘要

背景

热休克蛋白 90(Hsp90)抑制剂在卵巢癌(OC)中的潜在治疗效果存在争议。本研究旨在探讨外周血 Hsp90 水平与 OC 患者预后及临床病理指标的关系。

材料与方法

回顾性收集 2017 年至 2022 年安徽医科大学第一附属医院妇产科收治的 OC 患者的临床病理指标。采用酶联免疫吸附试验检测患者血液中 Hsp90 水平,系统研究 Hsp90 水平与 OC 预后的相关性。采用 Kaplan-Meier 法绘制生存曲线,计算平均生存时间和生存率。采用 log-rank 检验和 Cox 模型进行单因素生存分析,采用 Cox 比例风险模型进行多因素生存分析。基于 cBioPortal 获得的 OC 的 TCGA 数据集,计算 Hsp90 水平值与其他 mRNA 表达值之间的 Pearson 相关系数,进一步进行生物信息学分析。进行 GSEA 和 GSVA 分析进行基因功能富集。采用免疫组织化学染色评估和比较 OC 组织中 Hsp90 的表达。

结果

根据建立的筛选标准,共选择了 106 例患者。酶联免疫吸附试验结果显示,50.94%的 OC 患者 Hsp90 水平异常。根据 Kaplan-Meier 曲线的结果,结果表明 Hsp90 水平异常提示 OC 患者预后不良(P=0.001)。此外,多因素 Cox 比例风险回归模型分析结果也预测 Hsp90 水平异常(HR=2.838,95%CI=1.139-7.069,P=0.025)与不良预后相关,可作为 OC 患者预后的独立预后因素。此外,通过 Pearson 值与 Hsp90 相关的前 100 个基因表明,Hsp90 参与了 ATF5 靶基因、PRAGC1A 靶基因和 BANP 靶基因的调节,并且富集在细胞对 DNA 损伤刺激的反应、对热的反应和蛋白质折叠等代谢过程中。

结论

Hsp90 水平与 OC 死亡率呈正相关,是 OC 的潜在预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d53d/10230804/f44d08375bc1/12885_2023_10929_Fig1_HTML.jpg

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