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EVI1 和 PARP1 高表达可作为高级别浆液性卵巢癌的有利预后标志物。

High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinoma.

机构信息

Institute of Pathology, Philipps-University Marburg, University Hospital Marburg (UKGM), Marburg, Germany.

Institute of Pathology, Zytologie Und Molekulare Diagnostik, REGIOMED, Klinikum Coburg, Coburg, Germany.

出版信息

J Ovarian Res. 2023 Jul 31;16(1):150. doi: 10.1186/s13048-023-01239-6.

Abstract

BACKGROUND

Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC.

METHODS

For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection.

RESULTS

High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504-0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352-0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression.

CONCLUSIONS

EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.

摘要

背景

高级别浆液性卵巢癌(HGSOC)的发展和进展机制尚不清楚。EVI1 和 PARP1 是 TGF-β 通路的一部分,在具有 DNA 修复缺陷的癌症中上调,并且可能影响疾病进展和生存。因此,我们质疑 EVI1 单独和与 PARP1 联合表达的蛋白对 HGSOC 患者队列的预后意义,并对其进行了分析。

方法

我们通过组织微阵列上的免疫组织化学染色,使用 QuPath 数字半自动阳性细胞检测对 562 例 HGSOC 患者评估了 EVI1 和 PARP1 的表达。

结果

高表达 EVI1(>30%阳性肿瘤细胞)的 HGSOC 与无进展生存期(PFS)(HR=0.66,95%CI:0.504-0.852,p=0.002)和总生存期(OS)(HR=0.45,95%CI:0.352-0.563,p<0.001)相关,包括多变量分析。最有趣的是,这两种蛋白质的相互高表达确定了一组具有特别良好预后的患者。我们的发现通过单细胞测序、拷贝数变异以及基因和蛋白质表达的生物信息学数据集进行了技术和临床验证。

结论

EVI1 和 PARP1 是 HGSOC 预后良好的可靠生物标志物,并暗示了对其相互关系进行进一步研究的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2458/10388497/70ca82d10778/13048_2023_1239_Fig1_HTML.jpg

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