Function and diagnostic value of Anosmin-1 in gastric cancer progression

摘要

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 <600 pg/ml. ANOS1 may represent a biomarker for GC phenotypes and as a target for therapy.