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全基因组分析以鉴定胰十二指肠切除术后早期胰腺导管腺癌患者的预后标志物。

Genome-scale analysis to identify prognostic markers in patients with early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy.

作者信息

Liao Xiwen, Huang Ketuan, Huang Rui, Liu Xiaoguang, Han Chuangye, Yu Long, Yu Tingdong, Yang Chengkun, Wang Xiangkun, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University.

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning.

出版信息

Onco Targets Ther. 2017 Sep 12;10:4493-4506. doi: 10.2147/OTT.S142557. eCollection 2017.

Abstract

BACKGROUND

Molecular analysis is a promising source of clinically useful prognostic biomarkers. The aim of this investigation was to identify prognostic biomarkers for patients with early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy.

METHODS

An RNA sequencing dataset of PDAC was obtained from The Cancer Genome Atlas. Survival analysis and weighted gene co-expression network analysis were used to investigate the prognostic markers of early-stage PDAC after pancreaticoduodenectomy.

RESULTS

Using whole genome expression level screening, we identified 1,238 markers that were related to the prognosis of PDAC after pancreaticoduodenectomy, and identified 9 hub genes (, , , , , , , , and ) using the weighted gene co-expression network analysis approach. We also constructed a signature comprising the 9 hub genes and weighted by the regression coefficient derived from a multivariate Cox proportional hazards regression model to divide patients into a high-risk group, with increased risk of death, and a low-risk group, with significantly improved overall survival (adjusted =0.026, adjusted HR =0.513, 95% CI =0.285-0.924). The prognostic signature of the 9 genes demonstrated good performance for predicting 1-year overall survival (area under the respective receiver operating characteristic curves =0.641).

CONCLUSION

Our results have provided a new prospect for prognostic biomarkers of PDAC after pancreaticoduodenectomy, and may have a value in clinical application.

摘要

背景

分子分析是临床有用的预后生物标志物的一个有前景的来源。本研究的目的是识别胰十二指肠切除术后早期胰腺导管腺癌(PDAC)患者的预后生物标志物。

方法

从癌症基因组图谱获得PDAC的RNA测序数据集。使用生存分析和加权基因共表达网络分析来研究胰十二指肠切除术后早期PDAC的预后标志物。

结果

通过全基因组表达水平筛选,我们鉴定出1238个与胰十二指肠切除术后PDAC预后相关的标志物,并使用加权基因共表达网络分析方法鉴定出9个核心基因(、、、、、、、和)。我们还构建了一个由这9个核心基因组成的特征,并根据多变量Cox比例风险回归模型得出的回归系数进行加权,将患者分为死亡风险增加的高风险组和总生存期显著改善的低风险组(校正=0.026,校正HR=0.513,95%CI=0.285-0.924)。这9个基因的预后特征在预测1年总生存期方面表现良好(相应的受试者工作特征曲线下面积=0.641)。

结论

我们的结果为胰十二指肠切除术后PDAC的预后生物标志物提供了新的前景,可能具有临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ecc/5602474/8c5a412b0a38/ott-10-4493Fig1.jpg

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