Identification of annexin A1 as a proinvasive and prognostic factor for lung adenocarcinoma.
ABSTRACT Metastasis is the most common cause of death in lung cancer patients and is a major obstacle to the successful treatment. To discover novel metastasis-related proteins in lung adenorcinoma (AdC), quantitative proteomic analysis was performed between primary lung AdC tissues with (LNM AdC) and without lymph node metastasis (non-LNM AdC). In this study, annexin A1 was identified to be significantly up-regulated in LNM AdC compared with non-LNM AdC. Immunohistochemistry showed that annexin A1 over-expression was frequently observed in LNM AdCs and matched lymph node metastases compared with non-LNM AdCs. Annexin A1 over-expression was significantly associated with advanced clinical stage (P < 0.05) and lymph node metastasis (P < 0.05) and increased relapse rate (P < 0.05) and decreased overall survival (P < 0.05) in lung AdCs. Cox regression analysis indicated annexin A1 over-expression was an independent prognostic factor. Furthermore, suppression of annexin A1 expression by siRNA interference significantly inhibited the invasion ability of lung adenocarcinoma cell A549 in vitro. In conclusion, annexin A1 expression correlated with tumor stage, lymph node metastasis, relapse, and patient survival. Annexin A1 is proposed to function importantly in the progression of lung AdC.
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ABSTRACT: Gastric carcinoma (GC) is one of the most common malignancies worldwide. To identify the candidate carcinoma-related biomarker in GC, comparative proteome technique was performed in resected GC tissues and matched adjacent non-cancerous gastric tissues (ANGT). As a result, S100A2 was successfully identified to be down-regulated significantly in GC compared with ANGT. Western blot analysis validated decreased expression of S100A2, and its expression level was related with the degree of tumor differentiation and status of lymph node metastasis in GC. Furthermore, immunohistochemistry analysis showed S100A2 down-expression was significantly associated with poor differentiation (P < 0.05), advanced depth of invasion (P < 0.05) and lymph node metastasis (P < 0.05) in GC. Kaplan-Meier curves showed that the relapse-free probability and the overall survival rate were significantly decreased with S100A2 expression decreasing (P < 0.05). Cox regression analysis indicated S100A2 down-expression was a negative independent prognostic biomarker for GC. A supplement of S100A2 protein by S100A2 expression vector significantly decreased the number of invaded cancer cells MGC-803. However, knockdown of S100A2 expression by siRNA interference compromised the invasion ability of MGC-803 cells. Moreover, S100A2 negatively regulated MEK/ERK signaling pathway, and activation of this signaling pathway by S100A2 down-regulation increased in vitro invasion of MGC-803 cells. In conclusion, this study demonstrated the clinical significance of S100A2 expression in GC, and loss of S100A2 expression contributes to GC development and progression. Therefore, the determination of S100A2 expression levels contributes to predict the outcome of GC patients.Tumor Biology 12/2013; · 2.52 Impact Factor
Article: Potential role of Anxa1 in cancer.[Show abstract] [Hide abstract]
ABSTRACT: The annexins are a well-known, closely related, multigene superfamily of Ca(2+)-regulated, phospholipid-dependent, membrane-binding proteins. As a member of the annexins, Anxa1 participates in a variety of important biological processes, such as cellular transduction, membrane aggregation, inflammation, phagocytosis, proliferation, differentiation and apoptosis. Accumulated evidence has indicated that Anxa1 deregulations are associated with the development, invasion, metastasis, occurrence and drug resistance of cancers. The research evidence in recent years indicates that Anxa1 might specifically function either as a tumor suppressor or a tumor promoter candidate for certain cancers depending on the particular type of tumor cells/tissues. This article summarizes the associations between Anxa1 and malignant tumors, as well as potential action mechanisms. Anxa1 has the potential to be used in the future as a biomarker for the diagnosis, treatment and prognosis of certain tumors.Future Oncology 11/2013; 9(11):1773-93. · 3.20 Impact Factor
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ABSTRACT: Lung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD.Journal of translational medicine. 06/2014; 12(1):159.