TY - JOUR
T1 - Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival
AU - Li, Hong
AU - Wang, Yanru
AU - Liu, Hongliang
AU - Shi, Qiong
AU - Li, Hongyu
AU - Wu, Wenting
AU - Zhu, Dakai
AU - Amos, Christopher I.
AU - Fang, Shenying
AU - Lee, Jeffrey E.
AU - Li, Yi
AU - Han, Jiali
AU - Wei, Qingyi
N1 - Publisher Copyright:
© Li et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Cox regression
KW - Cutaneous melanoma
KW - PDGF signaling pathway
KW - Single nucleotide polymorphisms
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U2 - 10.18632/oncotarget.20245
DO - 10.18632/oncotarget.20245
M3 - Article
C2 - 29088810
AN - SCOPUS:85030101102
SN - 1949-2553
VL - 8
SP - 74595
EP - 74606
JO - Oncotarget
JF - Oncotarget
IS - 43
ER -