Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples
Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples
复制标题
DOI：
10.1111/j.1349-7006.2008.00935.x
复制
发表时间：
2008-11-01
期刊：
影响因子：
5.7
通讯作者：
Nishio, Kazuto
中科院分区：
文献类型：
--
作者：
Yamada, Yasuhide;Arao, Tokuzo;Nishio, Kazuto
化疗前的内镜活检为研究生物标志物预测胃癌患者的总生存率提供了机会。这项前瞻性研究旨在确定未切除胃癌患者的预后生物标志物。59例未经化疗的转移性胃癌患者入组本研究。使用40个活检样本进行微阵列分析，以确定其表达可能与总生存率相关的候选基因。基于多变量分析调整临床协变量后，在19个独立验证样本中使用实时逆转录聚合酶链反应（RT-PCR）分析验证所识别的基因。使用基于比例风险模型的微阵列分析鉴定了98个表达水平与总生存期显著相关的候选基因（P < 0.005）。进行多变量分析以评估这些基因中的10个，并且结果产生DACH 1和PDCD 6的统计学显著性水平。我们使用实时RT-PCR进一步评估了独立样本中的这两个基因，发现PDCD 6的mRNA表达水平较低与总体生存率低显著相关。我们使用内镜活检样本确定PDCD 6为未切除胃癌患者的预后生物标志物。我们基于PCR的单基因预测策略成功地预测了总生存率，并可能导致更好地了解这种疾病亚组。（Cancer Sci 2008; 99：2193-2199）。
Endoscopic biopsy prior to chemotherapy provides an opportunity for studying biomarkers to predict the overall survival in gastric cancer patients. This prospective study was performed to identify prognostic biomarkers in patients with unresected gastric cancer. Fifty-nine cases of chemotherapy-naive metastatic gastric cancer were enrolled in this study. A microarray analysis was performed using 40 biopsy samples to identify candidate genes whose expressions might be correlated with the overall survival. After adjusting for clinical covariates based on a multivariate analysis, the identified genes were validated using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis in 19 independent validation samples. Ninety-eight candidate genes whose expression levels were significantly correlated with the overall survival were identified using a microarray analysis based on a proportional hazards model (P < 0.005). Multivariate analysis was performed to assess 10 of these genes, and the results yielded a statistical significance level for DACH1 and PDCD6. We further evaluated these two genes in independent samples using real-time RT-PCR and found that lower mRNA expression levels of PDCD6 were correlated significantly with a poor overall survival. We identified PDCD6 as a prognostic biomarker in patients with unresected gastric cancer using endoscopic biopsy samples. Our PCR-based single gene prediction strategy successfully predicted the overall survival and may lead to a better understanding of this disease subgroup. (Cancer Sci 2008; 99: 2193-2199).