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Introduction
In recent years, there has been progress in treating gastric cancer (GC) with the widespread use of new surgical techniques for tumor resection and lymph node dissection. With the development of adjuvant chemotherapy and targeted molecular therapies, condition of patients have improved significantly (1). Although the incidence of GC has declined in recent years, it still remains the fifth most common cancer in the world. Patients with inoperable, metastatic or recurrent disease have very low survival rate, even after palliative cytotoxic chemotherapy (2).
Cancer stem cells (CSCs), which have roles in survival and chemoresistance, are commonly analyzed according to the expression of CD44 and CD24 markers (3). CD44 is a cell surface glycoprotein and an adhesion molecule which provides signal transduction through cell-cell communication. CD44 has several functions in migration, adhesion and signalization (4). The expression of CD44 was found to be correlated with survival, tumor size, stage and metastasis in GC (5). CD44 is also a GC stem cell marker and not only CD44+ GC cells were found to be chemoresistant, but the expression level of CD44 is associated with the onset and progression of gastric tumors (6, 7).
CD24, a cell surface protein linked to glycosylphosphotidyl- inositol, is a heat-stable antigen which is heavily glycosylated and involved in cell-cell and cell- matrix interactions (8). CD24 overexpression can inhibit an anti-apoptotic signaling pathway in CD44+ tumor cells and accelerate apoptosis as an answer to DNA damage (9). CD24 is also an important diagnostic and prognostic marker of cancer given its expression in many tumor types. In some types of cancer, such as breast cancer, CSCs have decreased CD24 expression (10). However, in certain tumor types, such as nasopharyngeal, it has been suggested as a CSCs marker (11). Accordingly, the status of CD24 as a CSC marker remains vague when compared with CD44.
mtDNA depletion is a common event in GC, which may induce CD44 expression in cancer cells (12-14). This depletion has been shown to induce the generation of CSCs, invasion and metastasis, and expression of epithelial-mesenchymal transition (EMT) markers. In addition, it promotes pro-survival and anti-apoptotic pathways which may lead to chemoresistance (13, 15, 16). In hepatocellular carcinoma and breast cancer, increased expression of antioxidant enzymes such as glutathione peroxidase and manganese...