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

Abstract

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.Although declining gradually in prevalence, gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer-related death worldwide. 1,2 Despite improvements in surgical techniques and chemotherapy, GC still represents a global public health problem with a 5-year overall survival of <25%. 3,4 Uncovering the molecular and cellular mechanisms involved in GC pathogenesis is pivotal to the development of more sensitive and specific biomarkers as well as enhanced molecular-targeting treatments that are required to overcome this devastating disease.GC is a phenotypically and genetically heterogeneous disease. [5][6][7] The main histological variants of GC are the intestinal type with clearly defined glandular structures and the diffuse type characterized by infiltrating neoplastic cells. 3 GC is etiologically associated with the combined effects of environmental factors and patients with predisposing genetic variants. 8,9 Moreover, the accumulation of genetic and epigenetic alterations contributes to the selection of neoplastic clones in a preferred tumor microenvironment. 6,10 The complicated molecular pathogenesis of GC caused by tumor heterogeneity makes it difficult to identify diagnostic and therapeutic targets that are useful for the management of patients. 7,11,12 A system for stratifying patients with GC according to genotype was proposed that facilitates the discovery of genes that contribute to the pathogenesis of GC.The Anosmin-1 (ANOS1) gene encodes cell adhesion protein that is a component of the extracellular matrix (ECM). 13 ANOS1...

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Adverse Effects of Intraoperative Blood Loss on Long-Term Outcomes after Curative Gastrectomy of Patients with Stage II/III Gastric Cancer

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