Zhou Ting, Lin Wei, Zhu Qiongni, Renaud Helen, Liu Xiaowei, Li Ruidong, Tang Cui, Ma Chong, Rao Tai, Tan Zhirong, Guo Ying
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China.
Human Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, People's Republic of China.
Onco Targets Ther. 2019 Jul 25;12:6001-6012. doi: 10.2147/OTT.S208060. eCollection 2019.
Imprinted genes are often identified as key players in the etiology and prognosis of many tumors; however, the role they play in colon cancer remains unclear. Along with the development of big data analysis came the discovery of a wealth of genetic prognostic factors, like microsatellite instability for colon cancer, which need to be taken into consideration when evaluating new biomarkers for the disease.
We systematically mined public databases to find recurrence free survival (RFS)-related imprinted genes for colon cancer patients on the mRNA level by univariate and multivariate survival analyses. We then investigated the association of methylation status and microRNA expression of the targeted imprinted genes with survival rate of colon cancer patients. Lastly, in a clinical study we used qRT-PCR and immunohistochemistry to quantify mRNA and protein expression of the imprinted genes that related to RFS in our bioinformatics screening, respectively, in 20 tumor tissues compared to paired adjacent tissues.
The results show that paternally expressed gene 3 (PEG3) is the only imprinted gene related to colon cancer patient prognosis on the mRNA level in our datasets, and high mRNA expression of PEG3 is associated with a poor prognosis. Furthermore, the methylation beta value of cg13960339, as well as the expression of 4 microRNAs, negatively correlated with PEG3 mRNA level and were correlated with the prognosis of colon cancer patients. Moreover, the expression of PEG3 mRNA in colon cancer is significantly lower, but PEG3 protein expression is significantly higher compared to that in normal tissues.
PEG3 is likely associated with the progression and prognosis of colon cancer.
印记基因常被认为是许多肿瘤病因和预后的关键因素；然而，它们在结肠癌中所起的作用仍不清楚。随着大数据分析的发展，发现了大量的遗传预后因素，如结肠癌的微卫星不稳定性，在评估该疾病的新生物标志物时需要考虑这些因素。
我们系统地挖掘公共数据库，通过单变量和多变量生存分析在mRNA水平上寻找与结肠癌患者无复发生存期（RFS）相关的印记基因。然后，我们研究了靶向印记基因的甲基化状态和微小RNA表达与结肠癌患者生存率的关联。最后，在一项临床研究中，我们使用qRT-PCR和免疫组织化学分别对生物信息学筛选中与RFS相关的印记基因在20个肿瘤组织及其配对的相邻组织中的mRNA和蛋白质表达进行定量。
结果表明，父系表达基因3（PEG3）是我们数据集中在mRNA水平上与结肠癌患者预后相关的唯一印记基因，PEG3的高mRNA表达与不良预后相关。此外，cg13960339的甲基化β值以及4种微小RNA的表达与PEG3 mRNA水平呈负相关，并与结肠癌患者的预后相关。此外，与正常组织相比，结肠癌中PEG3 mRNA的表达显著降低，但PEG3蛋白表达显著升高。
PEG3可能与结肠癌的进展和预后相关。
