The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.
<h4>Objective</h4>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 RTO...
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Public Library of Science (PLoS)
2014
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oai:doaj.org-article:8813e1cb07004ce2a0b7f0b8c9ae27fa2021-11-18T08:23:33ZThe KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.1932-620310.1371/journal.pone.0094167https://doaj.org/article/8813e1cb07004ce2a0b7f0b8c9ae27fa2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24732316/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Methods/materials</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Larissa J LeeElena RatnerMohamed UdumanKathryn WinterMarta BoekeKathryn M GrevenStephanie KingThomas W BurkeKelly UnderhillHarold KimRaleigh J BoulwareHerbert YuVinita ParkashLingeng LuDavid GaffneyAdam P DickerJoanne WeidhaasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94167 (2014) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| description |
<h4>Objective</h4>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.<h4>Methods/materials</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Larissa J Lee |
| title |
The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| title_short |
The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| title_full |
The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| title_fullStr |
The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| title_full_unstemmed |
The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. |
| title_sort |
kras-variant and mirna expression in rtog endometrial cancer clinical trials 9708 and 9905. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/8813e1cb07004ce2a0b7f0b8c9ae27fa |
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