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非编码 RNA(ncRNA)谱与上皮性卵巢癌病例患者预后的关联。

Noncoding RNA (ncRNA) Profile Association with Patient Outcome in Epithelial Ovarian Cancer Cases.

机构信息

Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

Oncology Venture, Hoersholm, Denmark.

出版信息

Reprod Sci. 2021 Mar;28(3):757-765. doi: 10.1007/s43032-020-00372-7. Epub 2020 Oct 30.

Abstract

Ovarian cancer (OC) is the second most frequent type of gynecological cancers worldwide. In the past decades, the development of novel diagnostic and prognostic biomarkers available for OC has been limited, reflecting by the lack of specificity of such markers or very costly management. Microarray expression profiling has shown very effective results in exploring new molecular markers for patients with OC. Nonetheless, most screenings are focused on mutations or expression of molecules that are translated into proteins, corresponding to only 2% of the total human genome. In order to account for the vast majority of transcripts, in the present exploratory study, we assessed the expression levels of a comprehensive panel of noncoding RNA in different subtypes of OC. We further evaluated their association with patient overall survival (OS) and aggressive forms of the disease, such as tumor type, stage, and chemotherapy resistance. By microarray profiling in a total of 197 epithelial OC patients (162 serous carcinomas, 15 endometrioid carcinomas, 11 mucinous carcinomas, and 9 clear cell carcinomas), we found two candidates, SNORA68 and SNORD74, which associated with OS and poor clinicopathological features. The overexpression of those two targets combined was correlated with shorter OS and progression-free survival. That association was further observed to correlate with a more aggressive form of the disease. Overall, the results indicate that a panel comprised of SNORA68 and SNORD74 may be clinically relevant, where patients could be offered a more individualized, targeted follow-up, given its further validation on future prospective clinical studies.

摘要

卵巢癌 (OC) 是全球第二常见的妇科癌症类型。在过去几十年中,用于 OC 的新型诊断和预后生物标志物的发展受到限制,这反映了这些标志物缺乏特异性或管理成本非常高。微阵列表达谱分析在探索 OC 患者新的分子标志物方面显示出非常有效的结果。尽管如此,大多数筛选仍集中在突变或翻译成蛋白质的分子的表达上,这仅占人类基因组的 2%。为了涵盖绝大多数转录本,在本探索性研究中,我们评估了不同 OC 亚型中非编码 RNA 的综合表达水平。我们进一步评估了它们与患者总生存期 (OS) 和疾病侵袭性形式(如肿瘤类型、分期和化疗耐药性)的关联。通过对总共 197 例上皮 OC 患者(162 例浆液性癌、15 例子宫内膜样癌、11 例黏液性癌和 9 例透明细胞癌)进行微阵列分析,我们发现了两个候选物,SNORA68 和 SNORD74,它们与 OS 和不良临床病理特征相关。这两个靶标的过表达与更短的 OS 和无进展生存期相关。这种关联进一步被观察到与疾病的侵袭性形式相关。总体而言,这些结果表明,由 SNORA68 和 SNORD74 组成的面板可能具有临床相关性,在未来的前瞻性临床研究中进一步验证后,患者可能会获得更个性化、更有针对性的随访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaad/7862201/659c89816920/43032_2020_372_Fig1_HTML.jpg

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