Abstract 115P
Background
KRAS activation and pathway upregulation have been demonstrated in preclinical and clinical prostate cancer (PCa), respectively. However, the mechanisms of KRAS deregulation have not comprehensively been studied in PCa. The aim of this study is to define the mechanisms that deregulate KRAS expression in PCa.
Methods
Linux-based scripts were utilized to retrieve KRAS-relevant genomic, transcriptomic and methylation data from the cancer genome atlas (TCGA) Firehose PCa cohort (n=500), which are domiciled in the Genome Data Commons database. A list of KRAS-relevant miRNA was retrieved from miRTarBase (https://mirtarbase.cuhk.edu.cn/∼miRTarBase/miRTarBase_2022/php/). The relationships of KRAS expression with promoter methylation and copy number alterations (CNAs) of KRAS, as well as KRAS-relevant miRNA, were interrogated with Independent Sample T and multiple linear correlation tests in SPSS version 29.
Results
Copy number analysis demonstrated that there were 38/498, 456/498 and 6/498 KRAS losses/deletions, wild-types/neutrals and gains/amplifications, respectively. There was a significant KRAS copy number-expression correlation. The KRAS CNA status, beta values of 28 KRAS methylation loci and expression values of 83 KRAS-relevant miRNAs were incorporated into a multiple linear regression to predict their interaction with KRAS expression. The analysis identified KRAS CNA (P<0.001), hsamir30c1 (P<0.001), hsamir330 (P<0.001), hsamir143 (P=0.010), and hsalet7a3 expression (P=0.002), as well as methylation locus cg17197538 (P=<0.001) as independent predictors of KRAS expression in the regression model. The results showed that KRAS expression in PCa was deregulated by CNAs, miRNA and epigenetic mechanisms.
Conclusions
This study has identified the mechanisms of KRAS expression deregulation in PCa to include KRAS CNAs, and miRNA and epigenetic mechanisms.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.