Li Ai-Lin, Zhou Xin, Wang Zhen-Ning, Song Yong-Xi, Gao Peng, Miao Yuan, Zhu Jin-Liang, Xu Hui-Mian
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Tumour Biol. 2012 Dec;33(6):2159-66. doi: 10.1007/s13277-012-0476-2. Epub 2012 Aug 19.
Single nucleotide polymorphisms (SNPs) in the promoter regions of non-metastatic cells 1 gene (NME1) may attribute to the changing of promoter activities. In addition, high NME1 protein levels are correlated with negative lymph node metastasis in gastric cancer. This study evaluated possible associations between SNPs in NME1 gene and gastric cancer susceptibility, clinicopathological parameters, or survival. We obtained formalin-fixed paraffin-embedded tissues from 404 gastric cancer patients and blood samples from 404 controls. SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A significant correlation between SNPs and lymph node metastases risk was found. Patients carrying TT genotype in rs16949649, AA genotype in rs3760468, TT genotype in rs3760469, CC genotype in rs2302254, and GG genotype in rs34214448 were correlated to greater numbers of lymph node metastases (P = 0.023 in rs16949649; P = 0.015 in rs3760468; P = 0.043 in rs3760469; P = 0.008 in rs2302254; and P = 0.021 in rs34214448, respectively). Moreover, the haplotype TATCG were associated with positive lymph node metastasis (P = 0.039) and lymphovascular invasion (P = 0.048) compared to the haplotype CTGTT carriers. Furthermore, patients carrying AA genotype in rs3760468 or the haplotype TATCG had poor survival in T4 subgroup (P = 0.038 in univariate and P = 0.014 in multivariate analysis for rs3760468, and P = 0.017 in univariate and P = 0.012 in multivariate analysis for TATCG, respectively). In conclusion, SNPs in NME1 gene may play an important role in regulating lymph node metastasis and, thus, affect survival in T4 subgroup of gastric cancer in a Northern Chinese population.
非转移性细胞1基因(NME1)启动子区域的单核苷酸多态性(SNP)可能导致启动子活性的改变。此外,NME1蛋白水平高与胃癌的阴性淋巴结转移相关。本研究评估了NME1基因中的SNP与胃癌易感性、临床病理参数或生存率之间的可能关联。我们从404例胃癌患者中获取了福尔马林固定石蜡包埋组织,并从404例对照中获取了血液样本。通过基质辅助激光解吸/电离飞行时间质谱对SNP进行基因分型。发现SNP与淋巴结转移风险之间存在显著相关性。携带rs16949649的TT基因型、rs3760468的AA基因型、rs3760469的TT基因型、rs2302254的CC基因型和rs34214448的GG基因型的患者与更多的淋巴结转移相关(rs16949649中P = 0.023;rs3760468中P = 0.015;rs3760469中P = 0.043;rs2302254中P = 0.008;rs34214448中P = 0.021)。此外,与单倍型CTGTT携带者相比,单倍型TATCG与阳性淋巴结转移(P = 0.039)和淋巴管浸润(P = 0.048)相关。此外,携带rs3760468的AA基因型或单倍型TATCG的患者在T4亚组中的生存率较差(rs3760468单因素分析中P = 0.038,多因素分析中P = 0.014;TATCG单因素分析中P = 0.017,多因素分析中P = 0.012)。总之,NME1基因中的SNP可能在调节淋巴结转移中起重要作用,从而影响中国北方人群胃癌T4亚组的生存率。