Abstract
Background:
To investigate the prognostic implication of genetic variants within the wingless (Wnt) antagonist genes (DKK, sFRP, and Axin2) in North Indian lung cancer patients.
Materials and Methods:
A total of 212 subjects were genotyped using polymerase chain reaction–restriction fragment length polymorphism technique for 18 polymorphic sites in DKK4, DKK3, DKK2, sFRP3, sFRP4, and Axin2. Overall survival (OS) was estimated using the Kaplan–Meier survival analysis, and adjusted hazard ratio (HR) was obtained using the Cox regression method.
Results:
It was observed that the unfavorable genotypes of the three DKK2 variants collectively (rs447372, rs419558, and rs17037102) exhibited a highly decreased rate of death (adjusted HR = 0.37, p = 0.03). Adenocarcinoma (ADCC) patients carrying the heterozygous (CT) genotype for DKK4 rs2073664 showed a better OS compared with wild genotype (log rank p = 0.01). The two exonic variants (148 and 1386) of Axin2 gene showed contrasting results, where the ADCC subjects having TT genotype for Axin2 148 showed a better prognosis (adjusted HR = 0.48, p = 0.003) and those with TT genotype for Axin2 1386 showed a poor prognosis in small-cell lung carcinoma patients (adjusted HR = 2.33, p = 0.02). The intronic Axin2 1712 + 19 variant on the other hand indicated a highly increased death risk in ADCC patients with GG genotype. Survival tree analysis depicted DKK4 rs2073664 as the major contributor in predicting the survival of the lung cancer patients. Node 3 exhibited the lowest death rate (HR = 0.04, p = 0.008) and better median survival time (9 months vs. 3 months) when compared with reference node.
Conclusions:
A cumulative effect of three variants of DKK2 gene along with DKK4 rs2073664 can jointly predict the survival as shown by tree analysis.
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Supplementary Material
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