Qiu Yue, Hu Yuan, Zhang Zuo-Yang, Ye Lei, Xu Fei-Hong, Schneider Marion E, Ma Xue-Ling, Du Yi-Xin, Zuo Xian-Bo, Zhou Fu-Sheng, Chen Gang, Xie Xu-Shi, Zhang Yan, Xia Hong-Zhen, Wu Ji-Feng, Du Wei-Dong
Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, People's Republic of China.
J Cancer Res Clin Oncol. 2014 Dec;140(12):2143-56. doi: 10.1007/s00432-014-1761-9. Epub 2014 Jul 10.
(1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer.
We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC).
We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10(-4), odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10(-4), OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r s = 0.164).
We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.
（1）研究骨桥蛋白（OPN）及其受体分化簇44（CD44）基因中的单核苷酸多态性（SNP）与胃癌易感性之间的关联。（2）探讨OPN和CD44在胃癌中的表达相关性。
我们采用Sequenom技术检测了中国汉族人群胃癌患者中这些基因的26个SNP，并通过组织芯片和免疫组织化学（IHC）检测了243例病例组织样本中OPN与CD44的联合表达。
我们发现OPN rs4754C>T和OPN rs9138C>A的次要等位基因与降低的胃癌风险仍密切相关（P = 1.53×10⁻⁴，优势比（OR）0.642，95%置信区间（CI）0.511 - 0.808；P = 1.59×10⁻⁴，OR 0.642，95%CI 0.510 - 0.809）。OPN变异体rs1126772A>G和CD44变异体rs353639A>C显著增加了胃癌风险（P = 0.042，OR 1.279，95%CI 1.008 - 1.622；P = 0.047，OR 1.334，95%CI 1.003 - 1.772）。OPN和CD44变异体的单倍型显著影响胃癌风险。临床数据表明，OPN的rs4754和rs9138与吸烟显著相关（P = 0.029，OR 0.343，95%CI 0.127 - 0.926；P = 0.029，OR 0.343，95%CI 0.127 - 0.926），OPN rs1126772与肿瘤-淋巴结-转移（TNM）分期（P = 0.025，OR 1.765，95%CI 1.073 - 2.905）和肿瘤分化（P = 0.031，OR 1.722，95%CI 1.049 - 2.825）相关。通过IHC在243例病例中的133例（54.7%）中观察到OPN表达，其与浆膜侵犯（P = 0.013）、TNM分期（P = 0.003）和淋巴结转移（P = 0.002）相关。在243例病例中的92例（37.9%）中发现CD44表达，其分别与肿瘤大小（P = 0.005）和淋巴结转移（P = 0.023）相关。OPN表达与CD44呈正相关（P = 0.01，rs = 0.164）。
我们发现OPN基因的多态性rs4754、rs9138和rs1126772以及CD44基因的rs353639与胃癌显著相关。我们的IHC数据表明，OPN和CD44蛋白的相互作用会促进胃癌的进展和转移。
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