Association of 3'UTR variations of EGFR and KRAS oncogenes with clinical parameters in lung cancer tumours

Abstract

Bacground Information

Lung cancer is one of the leading types of cancer deaths worldwide, with approximately 2 million people diagnosed with lung cancer each year. In this study, we aimed to determine the exonic and 3′UTR sequences of EGFR, PIK3CA and KRAS genes in 39 sporadic lung cancer tumors and to reveal the changes in the miRNA binding profile of tumors with somatic variation in the 3'UTR region and to examine the relationship of these changes with clinical parameters.

Results

A statistically significant correlation was found between the presence of miRNA that could not bind to the 3′UTR region due to variation in at least one of the EGFR or KRAS genes and the presence of metastasis in the tumor. At the same time, Kaplan-Meier analysis between those with and without alterations in the miRNA profile due to somatic variation in the 3′UTR region showed that survival was lower in those with miRNA alterations and this was statistically significant.

Conclusions

In our study, it was shown that variations in the 3′UTR regions of EGFR and KRAS oncogenes may cause increased expression of these oncogenes by preventing the binding of miRNAs, and it was suggested that this may be related to metastasis, survival and drug resistance mechanism.

Significance

In this study, we show that hsa-miR-124-3p, hsa-miR-506-3p, hsa-miR-1290 and hsa-miR-6514-3p are particularly prominent in lung carcinoma in relation to these biological pathways and the roles that variations in the 3′UTR regions of oncogenes may play in the carcinogenesis process.