Dataset Information

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.

SUBMITTER: Saperstein R

PROVIDER: S-EPMC10594459 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Noncoding RNA Profile in Reovirus Treated <i>KRAS</i>-Mutated Colorectal Cancer Patients.

Saperstein Rafael R Goel Sanjay S Maitra Radhashree R

Diseases (Basel, Switzerland) 20231016 4

<h4>Purpose</h4>To investigate the alterations in the expression of noncoding, micro, and small RNA expression during treatment with oncolytic reovirus in <i>KRAS</i>-mutated colorectal cancer.<h4>Methods</h4>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 ...[more]

PMID: 37873786

Similar Datasets

Project description:BackgroundThe molecular and clinical features of KRAS-mutated lung cancer patients treated with immunotherapy have yet to be characterized, which could guide the development of therapeutics targeting KRAS with potential immuno-oncology treatment combinations.Research questionDo KRAS-mutated patients with different subtypes and comutations have different clinical responses and overall survival (OS) to checkpoint inhibitors?Study design and methods87 patients with NSCLC at the City of Hope who received immune checkpoint inhibitors were identified and analyzed retrospectively. Tumor genomic alterations were extracted from the clinical data with next-generation sequencing using various platforms. Demographic, clinical, molecular, and pathological information was collected with the approval of the institutional review board of the City of Hope. OS was calculated if it was available at the study time point, and responses were determined according to the RECIST v1.1.ResultsAmong 87 patients, 32 had a KRAS G12C mutation (36.8%), 19 had G12V (21.9%), 18 had G12D (20.7%), 6 had G12A (6.9%), 3 had G12R (3.45%), and 10 had amplification (11.49%) and other uncommon mutations. G12D had a statistically significant Odds Ratio (OR) between patients who had responses and progression of the disease (OR (95% CI) = 0.31 (0.09-0.95), p < 0.05), with 5 G12D-mutated patients having responses and 11 G12D-mutated patients having progression of the disease. In the univariate analysis with OS, there was a trend of better OS in the G12D-mutated patients, with no statistically significant difference in terms of OS between the patients who had G12D mutation and the patients who had other KRAS mutations (HR (95% CI) = 0.53 (0.21-1.36), p = 0.185). The median OS was significantly worse with KRAS comutation CDKN2A/B loss (4.2 vs. 16.9 months, HR = 3.07 (1.09-8.69), p < 0.05) and MET (3.4 vs. 17 months, HR = 3.80 (1.44-10.05), p < 0.01), which were included for the multivariate analysis. The OS with other KRAS comutations was not statistically significant, including STK11 and KEAP1.ConclusionKRAS mutation subtypes such as G12D and comutations such as CDKN2/A and MET may modulate the immunotherapy responses and outcomes in lung cancer.