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解析上皮性卵巢癌的病理和基因组特征。

Decoding the pathological and genomic profile of epithelial ovarian cancer.

机构信息

Pathology Department, Salah Azaiez Institute, Tunis, 1006, Tunisia.

Biology Department, Laboratory of Mycology, Pathologies and Biomarkers (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, 2092, Tunisia.

出版信息

Sci Rep. 2024 Nov 19;14(1):28573. doi: 10.1038/s41598-024-80030-z.

Abstract

Ovarian cancer (OC) is one of the most common cancers in women, with a high mortality rate. Most of published studies have been focused on Caucasian populations, with the need to explore biological features and clinical outcomes of patients from other ethnicities. We described clinical outcome (progression-free survival and overall survival) and biomarkers associated with survival in a cohort of patients with OC from Tunisia. Using immunohistochemistry, we assessed the expression of 14 proteins known to be altered in OC in a cohort of 198 patients. We explored the correlation between protein expression and copy number alteration (CNA) profiles. FIGO stage, menopausal status and mismatch repair deficiency were associated with survival. ERBB2 amplification was correlated with high ERBB2 expression (OR = 69.32, p = 4.03 E-09), and high PDL1 expression was associated to CD274 amplification (OR = 4.97, p = 5.79 E-2). We identified a correlation between survival and exposure to two CNA signatures (MAPK pathway and BRCA-related homologous recombination deficiency). Moreover, Gama-H2AX protein expression was correlated with exposure to a genomic signature associated with homologous recombination deficiency. We observed that OC clinical and pathological characteristics of these patients from Tunisia were similar to those of Caucasian patients. We identified frequent CNA in this population that need to be confirmed in other sets from Africa.

摘要

卵巢癌(OC)是女性最常见的癌症之一,死亡率很高。大多数已发表的研究都集中在白种人群体,需要探索其他种族患者的生物学特征和临床结局。我们描述了突尼斯 OC 患者队列的临床结局(无进展生存期和总生存期)和与生存相关的生物标志物。我们使用免疫组织化学评估了在 198 名患者队列中已知在 OC 中改变的 14 种蛋白质的表达。我们探讨了蛋白表达与拷贝数改变(CNA)谱之间的相关性。FIGO 分期、绝经状态和错配修复缺陷与生存相关。ERBB2 扩增与高 ERBB2 表达相关(OR=69.32,p=4.03E-09),高 PDL1 表达与 CD274 扩增相关(OR=4.97,p=5.79E-2)。我们确定了生存与暴露于两个 CNA 特征(MAPK 途径和 BRCA 相关同源重组缺陷)之间的相关性。此外,Gama-H2AX 蛋白表达与暴露于与同源重组缺陷相关的基因组特征相关。我们观察到这些来自突尼斯的患者的 OC 临床和病理特征与白种人群体相似。我们在该人群中发现了频繁的 CNA,需要在非洲的其他队列中得到证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/814f/11577113/6b2fce1eba96/41598_2024_80030_Fig1_HTML.jpg

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