The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.

Authors

• Larissa J Lee
• Elena Ratner
• Mohamed Uduman
• Kathryn Winter
• Marta Boeke
• Kathryn M Greven
• Stephanie King
• Thomas W Burke
• Kelly Underhill
• Harold Kim
• Raleigh J Boulware
• Herbert Yu
• Vinita Parkash
• Lingeng Lu
• David Gaffney
• Adam P Dicker
• Joanne Weidhaas

Publication/Presentation Date

1-1-2014

Abstract

OBJECTIVE: To explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials.

METHODS/MATERIALS: The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type.

RESULTS: The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant.

CONCLUSIONS: The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.

Volume

9

Issue

4

First Page

94167

Last Page

94167

ISSN

1932-6203

Published In/Presented At

Lee, L. J., Ratner, E., Uduman, M., Winter, K., Boeke, M., Greven, K. M., King, S., Burke, T. W., Underhill, K., Kim, H., Boulware, R. J., Yu, H., Parkash, V., Lu, L., Gaffney, D., Dicker, A. P., & Weidhaas, J. (2014). The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. PloS one, 9(4), e94167. https://doi.org/10.1371/journal.pone.0094167

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

24732316

Department(s)

Administration and Leadership

Document Type

Article