Genetic Variant of NFIB is Associated With the Metastasis of Osteosarcoma in Chinese Population

Abstract

Variant rs7034162 in NFIB was reported to be associated with metastasis of osteosarcoma in European cases with genome-wide significance. Our purpose was to replicate the association of rs7034162 with the metastasis of osteosarcoma in the Chinese population and to further characterize the expression level of NFIB in osteosarcoma tissues. A total of 321 patients were included in this study. Variant rs7034162 was genotyped for each patient using the Taqman genotyping assay. Fifty-two cases of tumor tissues and adjacent normal tissues were collected during surgery. The χ2 test was used to investigate the association of rs7034162 with the metastasis of osteosarcoma. The Student t test was used to compare the gene expression between patients with metastasis and those without metastasis. The messenger RNA expression level of NFIB was then compared among different genotypes of rs7034162 with 1-way analysis of variance test. Ninety-three patients were found to have metastasis. Patients with genotype AA had remarkably higher incidence of metastasis than those with genotype TT (34.4% vs 17.1%, P = .002). Patients with metastasis were found to have significantly higher rate of allele A than those without metastasis (53.2% vs 43.9%, P = .03). The messenger RNA expression of NFIB was significantly lower in tumor tissues of patients with metastasis than in those without metastasis (0.00035 ± 0.00017 vs 0.00063 ± 0.0025, P < .001). Compared to patients with genotype TT, those with genotype AA had remarkably decreased expression of NFIB (0.00033 ± 0.0014 vs 0.00067 ± 0.00037, P = .01). Single-nucleotide polymorphism rs7034162 was associated with metastasis of osteosarcoma in the Chinese population possibly via downregulation of NFIB. Further network analyses revealing the related pathways can help elucidate the molecular mechanism of distant metastasis in patients with osteosarcoma.