Cancer stem cells biomarkers in gastric carcinogenesis.

Background: Gastric carcinogenesis is a multistep process, involving multiple molecular alterations, including changes in cancer stem cells (CSCs). The present investigation was undertaken to determine whether changes in cancer stem cells could be utilized as a marker of progression of gastric carcinogenesis by examining the expression of gastric CSCs at different stages of carcinogenesis.

Methods: Ninety-three cases with 31 in each group of chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), or gastric cancer (GC) were analyzed immunohistochemically for proliferating cell nuclear antigen (PCNA) and Bcl-xl as biomarkers of proliferation and apoptosis, respectively, and CD44, CD166, and LGR5 levels by qRT-PCR as markers of gastric CSCs. Additionally, the levels of P53 and phosphorylated form of epidermal growth factor receptor (p-EGFR) were examined.

Results: While the levels of each of these biomarkers were found to be low to moderate in CSG and CAG patients, they were markedly increased in GC patients, in whom co-expression of CD44 with LGR5 and CD166 with p-EGFR was found to be the highest. We have also observed that although the expression of different CSC markers as well as the levels of p-EGFR were increased in precancerous lesions (CSG and CAG), they are further augmented in GC suggesting that they may play a pivotal role in the development and progression of gastric cancer.

Conclusions: Our observations suggest that the progression to gastric carcinogenesis from preneoplastic lesions such as superficial gastritis and chronic atrophic gastritis is associated with induction of CSCs together with increase in cell proliferation and inhibition of apoptosis.