Function and diagnostic value of Anosmin-1 in gastric cancer progression
Function and diagnostic value of Anosmin-1 in gastric cancer progression
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DOI：
10.1002/ijc.29803
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发表时间：
2016-02-01
影响因子：
6.4
通讯作者：
Kodera, Yasuhiro
中科院分区：
文献类型：
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作者：
Kanda, Mitsuro;Shimizu, Dai;Kodera, Yasuhiro
胃癌（GC）是一个主要的全球性健康问题，迫切需要新的分子生物标志物，患者分层以及治疗靶点。Anosmin-1（ANOS1）基因编码的细胞粘附分子在多种恶性肿瘤中发挥不同的作用。我们进行了GC细胞系的全局表达谱分析和小干扰RNA（siRNA）实验，以确定ANOS1表达对表型的影响。我们评估了患者组织和血清中ANOS1 mRNA和蛋白水平与GC亚型临床病理因素的相关性。GC细胞系的ANOS 1 mRNA差异表达与ITGAV、FOXC 2和NODAL mRNA水平呈正相关，与TFPI 2水平呈负相关。抑制ANOS 1表达可降低胃癌细胞的增殖、侵袭和迁移能力。237例胃癌组织中ANOS1 mRNA的平均水平显著高于相应的癌旁组织。升高的ANOS 1水平与GC的表型、较短的无病生存期和总生存期显著相关。ANOS 1表达是弥漫性和远端非弥漫性胃癌的一个更重要的预后指标。血清中的ANOS 1浓度在健康受试者、局部GC和播散性GC的血清中依次增加。术前血清ANOS1>= 600 pg/ml的患者预后差于术前血清ANOS1>= 600 pg/ml的患者。
Gastric cancer (GC) is a major global health problem that urgently requires novel molecular biomarkers for patient stratification as well as therapeutic targets. Anosmin-1 (ANOS1) gene encodes a cell adhesion molecule that plays diverse roles in multiple malignancies. We performed global expression profiling of GC cell lines and small interfering RNA (siRNA) experiments to determine the effect of ANOS1 expression on phenotype. We evaluated the association of ANOS1 mRNA and protein levels in patients' tissue and sera with clinicopathological factors of GC subtypes. Differential expression of ANOS1 mRNA by GC cell lines correlated positively to levels of ITGAV, FOXC2 and NODAL mRNAs and inversely with those of TFPI2. Inhibiting ANOS1 expression decreased the proliferation, invasion and migration of GC cells. The mean level of ANOS1 mRNA was significantly higher in 237 GC tissues compared with the corresponding noncancerous adjacent tissues. Elevated ANOS1 levels associated significantly with the phenotypes of GC, shorter disease-free and overall survival. ANOS1 expression was a more significant prognostic marker for diffuse and distal nondiffuse GC. ANOS1 concentrations in sera increased sequentially in sera of healthy subjects, localized GC and disseminated GCs. Prognosis was worse for patients with preoperative serum ANOS1 >= 600 pg/ml compared with those with