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并且突变状态与卵巢癌中的[具体未提及内容]及表达相关。

and mutation status associates with and expression in ovarian cancer.

作者信息

Wieser Verena, Gaugg Inge, Fleischer Martina, Shivalingaiah Giridhar, Wenzel Soeren, Sprung Susanne, Lax Sigurd F, Zeimet Alain G, Fiegl Heidelinde, Marth Christian

机构信息

Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck 6020, Austria.

Division of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria.

出版信息

Oncotarget. 2018 Apr 3;9(25):17501-17511. doi: 10.18632/oncotarget.24770.

Abstract

Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral and mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of , and by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 () and breast cancer gene 1/2 () mutation status. -mutated OC strongly expressed compared to wild-type OC ( = 0.028) and -mutated OC increasingly expressed ( = 0.024) and ( = 0.012) compared to wild-type OC. For the first time in human, we noted a strong correlation between tumoral and or mRNA-expression, respectively ( < 0.001). OC tissue increasingly expressed compared to healthy controls (vs. ovaries: < 0.001; vs. tubes: = 0.018). and mRNA-expression increased with higher tumor grade ( = 0.008 and = 0.027, respectively) and younger age (< median age, = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high and mRNA-expression was associated with reduced progression-free ( = 0.024) and overall survival ( = 0.049) but only in the univariate analysis. Our study suggests that in OC / mRNA-expression is controlled by and affected by and mutations. We suggest that these mutations might serve as potential predictive factors that guide anti-/ immunotherapy.

摘要

程序性细胞死亡蛋白1(PD-1)及其配体PD-L1等检查点分子是肿瘤免疫逃逸的关键要素。本研究的目的是调查一组卵巢癌(OC)患者的肿瘤组织及mRNA表达与肿瘤突变的关系。我们通过定量实时PCR分析了170例低级别浆液性(LGSOC)、高级别浆液性(HGSOC)、子宫内膜样和透明细胞OC患者组织中 、 和 的mRNA表达,并与28个非病变组织(卵巢和输卵管)进行比较,同时分析其与肿瘤蛋白53( )和乳腺癌基因1/2( )突变状态的关系。与 野生型OC相比, 突变的OC强烈表达 ( = 0.028),与 野生型OC相比, 突变的OC越来越多地表达 ( = 0.024)和 ( = 0.012)。在人类中,我们首次发现肿瘤组织中 和 或 的mRNA表达之间存在强烈相关性( < 0.001)。与健康对照相比,OC组织中 表达增加(与卵巢相比: < 0.001;与输卵管相比: = 0.018)。 和 的mRNA表达随着肿瘤分级升高(分别为 = 0.008和 = 0.027)和年龄较轻(<中位年龄, = 0.001)而增加。最后,在我们队列的主要亚组,即国际妇产科联盟(FIGO)III/IV期HGSOC中,高 和 mRNA表达与无进展生存期缩短( = 0.024)和总生存期缩短( = 0.049)相关,但仅在单因素分析中。我们的研究表明,在OC中, / mRNA表达受 控制,并受 和 突变影响。我们认为这些突变可能作为指导抗 /免疫治疗的潜在预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7c2/5915132/ec56905ba47b/oncotarget-09-17501-g001.jpg

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