Department of Obstetrics & Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Br J Cancer. 2012 Jun 26;107(1):91-9. doi: 10.1038/bjc.2012.217. Epub 2012 May 29.
The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours.
To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas.
Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively).
We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.
本研究旨在鉴定在化学敏感性浆液性乳头状卵巢癌中与化学抗性肿瘤中表达不同的基因。
为了鉴定新的候选生物标志物,我们分析了 26 例 IIIC/IV 期浆液性卵巢腺癌(12 例化学敏感性肿瘤和 14 例化学抗性肿瘤)中基因表达的差异。随后,我们在 48 组独立的晚期卵巢浆液性癌中研究了 GRIA2 的免疫组织化学表达。
微阵列分析显示,在化学抗性和化学敏感性肿瘤中共有 57 个基因表达差异。在这 57 个基因中,有 39 个基因在化学敏感性肿瘤中上调,18 个基因下调。通过实时定量 PCR 验证了 5 个差异表达基因(CD36、LIFR、CHL1、GRIA2 和 FCGBP)。通过免疫组织化学验证了 GRIA2 的表达,GRIA2 表达的患者具有更长的无进展生存期和总生存期(P=0.051 和 P=0.031)。
我们发现了 57 个差异表达基因,可以区分化学敏感性和化学抗性肿瘤。我们还证明,在差异表达基因中,GRIA2 的表达为晚期浆液性乳头状卵巢腺癌患者提供了更好的预后。