Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival

Hong Li, Yanru Wang, Hongliang Liu, Qiong Shi, Hongyu Li, Wenting Wu, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, Yi Li, Jiali Han, Qingyi Wei

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Abstract

To investigate whether genetic variants of platelet-derived growth factor (PDGF) signaling pathway genes are associated with survival of cutaneous melanoma (CM) patients, we assessed associations of single-nucleotide polymorphisms in PDGF pathway with melanoma-specific survival in 858 CM patients of M.D. Anderson Cancer Center (MDACC). Additional data of 409 cases from Harvard University were also included for further analysis. We identified 13 SNPs in four genes (COL6A3, NCK2, COL5A1 and PRKCD) with a nominal P < 0.05 and false discovery rate (FDR) < 0.2 in MDACC dataset. Based on linkage disequilibrium, functional prediction and minor allele frequency, a representative SNP in each gene was selected. In the metaanalysis using MDACC and Harvard datasets, there were two SNPs associated with poor survival of CM patients: rs6707820 C > T in NCK2 (HR = 1.87, 95% CI = 1.35-2.59, Pmeta = 1.53E-5); and rs2306574 T > C in PRKCD (HR = 1.73, 95% CI = 1.33-2.24, Pmeta = 4.56E-6). Moreover, CM patients in MDACC with combined risk genotypes of these two loci had markedly poorer survival (HR = 2.47, 95% CI = 1.58-3.84, P < 0.001). Genetic variants of rs6707820 C > T in NCK2 and rs2306574 T > C in PRKCD of the PDGF signaling pathway may be biomarkers for melanoma survival.

Original languageEnglish (US)
Pages (from-to)74595-74606
Number of pages12
JournalOncotarget
Volume8
Issue number43
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Cox regression
  • Cutaneous melanoma
  • PDGF signaling pathway
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Oncology

Cite this

Li, H., Wang, Y., Liu, H., Shi, Q., Li, H., Wu, W., Zhu, D., Amos, C. I., Fang, S., Lee, J. E., Li, Y., Han, J., & Wei, Q. (2017). Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival. Oncotarget, 8(43), 74595-74606. https://doi.org/10.18632/oncotarget.20245