Abstract
This study aims to investigate the prognostic power of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in gastric cancer (GC) and its potential role in cancer development and progression. Data mining results show that CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis. Subsequently, immunohistochemical staining was performed to determine CEACAM6 protein levels in paraffin gastric tumor specimens. Real-time reverse-transcription-polymerase chain reaction (RT-PCR) was conducted to detect CEACAM6 mRNA levels in fresh GC samples. CEACAM6 protein and mRNA levels were significantly up regulated in GC compared with paired normal mucosa. The IHC staining intensity of CEACAM6 was positively correlated with tumor size, Lauren's classification, vascular invasion, lymph node metastasis, distant metastasis, and TNM stage. CEACAM6 expression was inversely correlated with the five-year survival rate of GC patients. Cox multivariate analysis results demonstrated that the overall survival was independently correlated with CEACAM6 expression. A significant association was observed between CEACAM6 and distant metastases. Network analysis of downstream gene signatures revealed several hub genes such as SRC and DNM1L etc. which may mediating tumor promoting functions of CEACAM6. Further data mining discovered that Tamoxifen etc. could be therapeutic alternatives for gastric patients with CEACAM6 overexpression. Collectively, CEACAM6 overexpression is a common characteristic of GC and is associated with poor 5 year survival rate in GC. Besides, potential molecular mechanisms and treatment options were also provided.
Highlights
Gastric cancer (GC) is one of the most common causes of cancer-related mortality worldwide with an estimated 951,600 new cases and 723,100 deaths occurred in 2012 [1, 2]
Data mining results show that carcinoembryonic antigenrelated cell adhesion molecule 6 (CEACAM6) is overexpressed in gastric cancer and is correlated with lymph node metastasis
CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis in several datasets
Summary
Gastric cancer (GC) is one of the most common causes of cancer-related mortality worldwide with an estimated 951,600 new cases and 723,100 deaths occurred in 2012 [1, 2]. Various cell adhesion molecules (CAMs) participate in the invasion and metastasis process during cancer progression [5]. Dysregulation of CAM expression and function has been found in malignant transformation. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family are transmembrane glycoproteins that belong to the immunoglobulin superfamily. They are involved in several biological processes [6], such as cell growth, differentiation, cell recognition, immune response, and adhesion [7,8,9,10]. Theses CEACAMs members can mediate several cell signaling pathways and lead to various functions, such as tumor suppression/promotion, angiogenesis, lymphocyte activation, cell cycle and adhesion [14,15,16]. CEACAM 1, 5, and 6 are co-expressed in endometrial, lung, ovarian, cervical, breast and colon cancers [17,18,19]
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