Noncoding RNA Profile in Reovirus Treated KRAS-Mutated Colorectal Cancer Patients

Abstract

Purpose: To investigate the alterations in the expression of noncoding, micro, and small RNA expression during treatment with oncolytic reovirus in KRAS-mutated colorectal cancer. Methods: Oncolytic reovirus treatment was administered in phase 1 clinical trial (NCT01274624) for 5 days every 28 days, and blood samples were collected before the administration of the reovirus and 48 h, 8 days, and 15 days after its administration on day 1. Data from the blood samples were sorted using Transcriptome Analysis Software (TAC) 4.0, where a two-tailed t-test and a fold change filter were used to ascertain which sample signals had a statistically significant relative fold change of greater than 2 at multiple timepoints before or after oncolytic reovirus administration. Results: The long noncoding RNA’s RP11-332M2.1 (−6.1 x), LINC01506 (−16.18 x), and LINC00534 (−1.94 x) were downregulated at 48 h after reovirus administration [p < 0.05]. ncRNA’s EPB41L4A-AS1 (−6.34 x, 48 h; 11.99 x, day 8), JAK2 (2.2 x, 48 h; −2.23 x, day 8), ANXA4 (20.47 x, day 8; −7.54 x, day 15), and PCDH9 (−2.09, day 8; 1.82 x, day 15) were affected by the reovirus treatment and reflected the progress of the treatment [p < 0.05]. The small RNA SNORA26 (−1.59 x, day 8) was downregulated 48 h after the reovirus administration [p < 0.05]. The microRNA MIR-4461 (6.18 x, day 8; −3.76 x, day 15) was also affected by the reovirus administration [p < 0.05]. Conclusion: The administration of oncolytic reovirus to treat KRAS-mutated colorectal cancer is reflected in a noncoding RNA profile, and expression levels of the ncRNAs in that profile may thus be able to be used as a potential predictive marker for reovirus-treated colorectal cancer.