Dual role of carcinoembryonic antigen-related cell adhesion molecule 6 expression in predicting the overall survival of gastric cancer patients

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.

CEACAM6 promotes cisplatin resistance in lung adenocarcinoma and is regulated by microRNA‐146a and microRNA‐26a

“…Furthermore, CEACAM6 expression is significantly upregulated in LUAD in TCGA database, and CEACAM6 mRNA overexpression is associated with poor overall survival as previously reported. 7 Previous studies have also demonstrated that CEACAM6 overexpression in gastric cancer (GC) cells increased apoptotic resistance to 5-FU, 15 while gene silencing of CEACAM6 in pancreatic ductal adenocarcinoma BxPC3 cells resulted in improved sensitivity to gemcitabine through modulation of AKT activity in a Src-dependent manner. 16 However, how CEACAM6 is associated with drug resistance of cancer cells has not yet been fully clarified.…”

Therapeutic Effect of pHLIP-mediated CEACAM6 Gene Silencing in Lung Adenocarcinoma

“…Overexpression of CEACAM6 promotes cancer progression by inducing aberrant cell differentiation, anti-apoptosis, proliferation, and resistance to therapeutic agents 7 . Because a number of human adenocarcinomas express higher levels of CEACAM6 than other histologic subtypes, these results may have direct translational implications for the treatment of various human adenocarcinomas 7–17 . Several studies have explored the therapeutic targeting of CEACAM6 in various cancers using immunotherapeutic agents such as immunotoxin-based therapy 36 , monoclonal antibodies 6 , anti-CEACAM6 single chain variable fragment 37 , and antibody-drug conjugates 38 .…”

“…CEACAM6 is involved in cell adhesion, proliferation, migration, and invasion, as well as tumour cell metastasis 3,6 . It is overexpressed in a wide variety of carcinomas, including NSCLC and pancreatic, colon, breast, gastric, and hepatocellular carcinomas 7–17 . In NSCLC, lung adenocarcinomas express higher levels of CEACAM6 protein than other histologic subtypes.…”

Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?

“…Increased expression of CEACAM6 promotes tumor metastasis, antiapoptosis, and angiogenesis in pts. with advanced-stage gastric cancer [18]. Overexpression of CAECAM6 is associated with an aggressive phenotype mediated via TGF β , AKT, FAK, and SRC signaling [19].…”