Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: PEG3 is likely associated with the progression and prognosis of colon cancer.
Keywords: PEG3; colon cancer; imprinted gene; prognosis.