Identification of genes in patients for predicting ulcerative colitis-associated colorectal cancer

Abstract

Aim: Ulcerative colitis (UC) has been considered a risk factor for colorectal cancer (CRC). However, effective biomarkers for predicting UC-associated CRC are lacking. Therefore, it is necessary to screen biomarkers associated with UC-related CRC, which could be used to evaluate UC-associated CRC early, and provide possible mechanisms involved in UC-associated CRC. Efficient bioinformatics analysis could help to explore potential biomarkers. Method: Two public datasets, including 44 UC without CRC samples and 17 UC-associated CRC samples were chosen from Gene Expression Omnibus (GEO) database. Sva package was used to remove batch effects, and then we screened out differentially expressed genes (DEGs) with the limma package. STRING and Cytoscape were used to achieve protein-protein interaction (PPI) network analysis and hub genes. The survival curves between high and low gene expression were performed by a log-rank test based on the cancer genome atlas (TCGA) program. To validate the hub gene expression, we compared their expression between normal and colorectal cancer based on Oncomine. Furthermore, immunohistochemistry was used to validate the expression of selected differentially expressed proteins Results: 405 DEGs were identified, including 256 down-regulated genes and 149 up-regulated genes in UC-associated CRC tissues. 16 hub genes were identified. And among them, RPL6, RPL7, and RPL35 were related to the poor prognosis of patients. Higher expression of RPL6, RPL7, and RPL35 was validated in CRC tissues based on Oncomine. Moreover, higher expression of RPL7 was observed in CRC sample tissues compared to normal colorectal tissues(p=0.004) or UC tissues (p=0.009). However, the expression of RPL6 and RPL35 in CRC tissues was not significantly increased compared to UC tissues or normal tissues. Conclusion: Our study showed that overexpressed RPL7 may be a potential tumor oncogene and could act as a prognostic factor in clinical diagnosis and treatment during UC-associated CRC.