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Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival.

Publication ,  Journal Article
Yuan, H; Liu, H; Liu, Z; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q
Published in: Int J Cancer
August 1, 2015

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 (i.e., MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3 and TEAD4) 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 YAP1 rs11225163 CC, TEAD1 rs7944031 AG+GG and TEAD4 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 YAP1 rs11225163, TEAD1 rs7944031 and TEAD4 rs1990330, may independently or jointly modulate survival of CM patients. Additional large, prospective studies are needed to validate these findings.

Duke Scholars

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 1, 2015

Volume

137

Issue

3

Start / End Page

638 / 645

Location

United States

Related Subject Headings

  • Young Adult
  • YAP-Signaling Proteins
  • Transcription Factors
  • TEA Domain Transcription Factors
  • Signal Transduction
  • ROC Curve
  • Protein Serine-Threonine Kinases
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Phosphoproteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yuan, H., Liu, H., Liu, Z., Zhu, D., Amos, C. I., Fang, S., … Wei, Q. (2015). Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival. Int J Cancer, 137(3), 638–645. https://doi.org/10.1002/ijc.29429
Yuan, Hua, Hongliang Liu, Zhensheng Liu, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, and Qingyi Wei. “Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival.Int J Cancer 137, no. 3 (August 1, 2015): 638–45. https://doi.org/10.1002/ijc.29429.
Yuan H, Liu H, Liu Z, Zhu D, Amos CI, Fang S, et al. Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival. Int J Cancer. 2015 Aug 1;137(3):638–45.
Yuan, Hua, et al. “Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival.Int J Cancer, vol. 137, no. 3, Aug. 2015, pp. 638–45. Pubmed, doi:10.1002/ijc.29429.
Yuan H, Liu H, Liu Z, Zhu D, Amos CI, Fang S, Lee JE, Wei Q. Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival. Int J Cancer. 2015 Aug 1;137(3):638–645.

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

August 1, 2015

Volume

137

Issue

3

Start / End Page

638 / 645

Location

United States

Related Subject Headings

  • Young Adult
  • YAP-Signaling Proteins
  • Transcription Factors
  • TEA Domain Transcription Factors
  • Signal Transduction
  • ROC Curve
  • Protein Serine-Threonine Kinases
  • Prognosis
  • Polymorphism, Single Nucleotide
  • Phosphoproteins