Abstract
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of the glycosylphosphatidylinositol-linked immunoglobulin superfamily that is implicated in many human cancers. Here, we aimed to investigate the role of CEACAM6 expression in predicting the overall survival (OS) in gastric cancer (GC). The impact of CEACAM6 on the survival of patients with GC (n = 876) was assessed using an online Kaplan-Meier plotter. Findings were validated using the OS data of patients (n = 160) recruited from Ruijin Hospital. We found that high CEACAM6 expression was associated with a better OS in early-stage or well-differentiated GC, or who were treated without 5-fluorouracil (5-FU). Conversely, high CEACAM6 expression was associated with a poor OS in advanced-stage GC, poorly differentiated tumors, or who were treated with 5-FU. Furthermore, CEACAM6 may serve as a better marker for predicting OS in GC than CEA. In addition, CEACAM6 overexpression in GC cells increased apoptotic resistance to 5-FU. Moreover, CEACAM6 induced cluster of differentiation 4- and 8-positive lymphocytes were detected in early-stage GC. In conclusion, CEACAM6 plays a contradictory role in predicting the OS in GC. In early-stage GC, high CEACAM6 expression is associated with improved OS. However, in advanced-stage GC, high CEACAM6 expression is associated with a poor OS.
Highlights
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide[1, 2]
To identify those factors that contribute to these observations, stratified analysis was performed to evaluate the prognostic significance of Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and CEA expression in early- and advanced-stage gastric cancer (GC)
High CEACAM6 expression was associated with a poor overall survival (OS) in patients with Stage IV GC (P < 0.05; Fig. 1E)
Summary
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide[1, 2]. According to the latest cancer statistics, GC is the leading cause of cancer-related deaths in China followed by lung cancer[6]. Overall survival (OS) is considered the most important endpoint for evaluating cancer prognosis and is affected by many factors including tumor stage, differentiation, lymph node metastasis, and chemotherapy resistance[8,9,10]. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5/CEA) and CEACAM6 are members of the glycosylphosphatidylinositol-linked immunoglobulin superfamily that are overexpressed in a variety of human cancers[11], in gastrointestinal cancer[12, 13] and serve as tumor markers for predicting the prognosis of cancer patients[14, 15]. We used Kaplan-Meier plotter to assess the survival of patients with GC22. We subsequently analyzed the effects of these factors on the OS of patients with GC to better predict prognosis and guide treatment
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