Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma‐specific survival. Issue 3 (28th January 2015)

• Record Type: Journal Article
• Authors: Yuan, Hua; Liu, Hongliang; Liu, Zhensheng; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Wei, Qingyi
• Is Part Of: International journal of cancer. Volume 137:Issue 3(2015:Aug. 01)
• Page Start: 638
• Page End: 645
• Publication Date: 2015-01-28
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29429
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Cutaneous melanoma (CM) is the most lethal form of skin cancers. The Hippo pathway controls cell migration, development and sizes of the organs in diverse species, and deregulation of this pathway may affect CM progression and prognosis. Therefore, we hypothesized that genetic variants of Hippo pathway genes might predict survival of CM patients. We used the genotyping data of 1, 115 common single nucleotide polymorphisms (SNPs) in the 12 pathway core genes (<italic>i.e</italic>., <italic>MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3</italic> and <italic>TEAD4</italic>) from the dataset of our previously published CM genome‐wide association study and comprehensively analyzed their associations with CM‐specific survival (CSS) in 858 CM patients by using the Kaplan–Meier analyses and Cox proportional hazards regression models. We found a predictive role of <italic>YAP1</italic> rs11225163 CC, <italic>TEAD1</italic> rs7944031 AG+GG and <italic>TEAD4</italic> rs1990330 CA+AA in the prognosis of CM. In addition, patients with an increasing number of unfavorable genotypes (NUG) had a markedly increased risk of death. After incorporating NUG in the model with clinical variables, the new model showed a significantly improved discriminatory ability to classify CSS (AUC increased from 82.03% to 84.56%). Our findings suggest that genetic variants of Hippo pathway genes, particularly <italic>YAP1</italic> rs11225163, <italic>TEAD1</italic> rs7944031 and <italic>TEAD4</italic> rs1990330, may independently or jointly modulate survival of CM patients. Additional large, prospective studies are needed to validate these findings.</p> </abstract>