Zuo Shuguang, Dai Gongpeng, Ren Xuequn
1Center for Translational Medicine, Huaihe Hospital of Henan University, Kaifeng, 475001 Henan Province China.
2Institute of Infection and Immunity, Huaihe Hospital of Henan University, Kaifeng, 475001 Henan Province China.
Cancer Cell Int. 2019 Jan 5;19:6. doi: 10.1186/s12935-018-0724-7. eCollection 2019.
An accurate and robust gene signature is of the utmost importance in assisting oncologists to make a more accurate evaluation in clinical practice. In our study, we extracted key mRNAs significantly related to colorectal cancer (CRC) prognosis and we constructed an expression-based gene signature to predict CRC patients' survival.
mRNA expression profiles and clinicopathological data of colon adenocarcinoma (COAD) cases and rectum adenocarcinoma (READ) were collected from The Cancer Genome Atlas database to investigate gene expression alteration associated to the prognosis of CRC. Differentially expressed mRNAs (DEMs) were detected between COAD/READ and normal tissue samples. Relying on a univariate and multivariate Cox regression analyses, a mRNA panel signature was established and used for predicting the overall survival (OS) in CRC patients. Receiver operating characteristic curve was used to evaluate the prognosis performance of our model through calculating the AUC values corresponding to the 3-year and 5-year survival. To assess the performance of gene signature in the given cancer subgroups (CRC entire cohort, COAD cohort, and READ cohort), a stratified analysis was carried out according to clinical factors.
A total of 5341 and 5594 DEMs were collected from COAD vs. normal tissue samples, and READ vs. normal samples respectively. A univariate regression analysis for the common DEMs between COAD and READ cohorts resulted in 14 common mRNAs related to OS. The multivariate Cox regression analysis revealed that 6 of these mRNAs (EPHA6, TIMP1, IRX6, ART5, HIST3H2BB, and FOXD1) had significant prognostic value allowing the discrimination between high- and low-risk patients, implying poor and good outcomes, respectively. The stratified analysis identified 6-gene signature as an independent prognostic signature in predicting CRC patients' survival.
The 6-gene signature could act as an independent biomarker for survival prediction of CRC patients.
准确且可靠的基因特征对于帮助肿瘤学家在临床实践中进行更准确的评估至关重要。在我们的研究中，我们提取了与结直肠癌（CRC）预后显著相关的关键mRNA，并构建了基于表达的基因特征来预测CRC患者的生存情况。
从癌症基因组图谱数据库收集结肠腺癌（COAD）病例和直肠腺癌（READ）的mRNA表达谱及临床病理数据，以研究与CRC预后相关的基因表达改变。检测COAD/READ与正常组织样本之间差异表达的mRNA（DEM）。依靠单变量和多变量Cox回归分析，建立一个mRNA组特征并用于预测CRC患者的总生存期（OS）。通过计算对应3年和5年生存的AUC值，使用受试者工作特征曲线评估我们模型的预后性能。为了评估基因特征在给定癌症亚组（CRC全队列、COAD队列和READ队列）中的性能，根据临床因素进行分层分析。
分别从COAD与正常组织样本以及READ与正常样本中收集到共5341个和5594个DEM。对COAD和READ队列之间的共同DEM进行单变量回归分析，得到14个与OS相关的共同mRNA。多变量Cox回归分析显示，其中6个mRNA（EPHA6、TIMP1、IRX6、ART5、HIST3H2BB和FOXD1）具有显著的预后价值，能够区分高风险和低风险患者，分别意味着预后不良和良好。分层分析确定6基因特征是预测CRC患者生存的独立预后特征。
6基因特征可作为CRC患者生存预测的独立生物标志物。
