Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer

Abstract

Background:In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers’ roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers’ clinicopathological features and association with prognosis in patients with gastric cancer.Methods:Eligible studies were identified and odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Heterogeneity and sensitivity were analyzed as well. Publication bias was assessed using funnel plots and Egger tests.Results:The meta-analysis included 26 studies involving 4729 patients. High expression of CD44 was associated with Lauren type (intestinal type) (OR, 1.53 [95% CI, 1.02–2.30]; P = 0.038) and lymphatic vessel invasion (OR, 1.36 [95% CI, 1.06–1.76]; P = 0.021). CD133 overexpression was related to high TNM stage (III/IV) (OR, 3.18 [95% CI, 2.48–4.07]; P = 0.000), high depth of invasion (T3/T4) (OR, 2.97 [95% CI, 2.20–4.03]; P = 0.000), lymph node metastasis (OR, 2.82 [95% CI, 2.16–3.69]; P = 0.000), vascular invasion (OR, 6.71 [95% CI, 1.63–27.63]; P = 0.008), and distant metastasis (OR, 2.32 [95% CI, 1.64–3.29]; P = 0.000). In addition, survival analysis demonstrated a significant association between CD44, as well as CD133 and poor 5-year overall survival (HR, 1.87 [95% CI, 1.55–2.26]; P = 0.000; HR, 2.07 [95% CI, 1.76–2.44]; P = 0.000, respectively).Conclusion:These data suggest that upregulated expression of CD44 and CD133 correlates with several clinicopathological features and poor prognosis. Since the related features do not overlap, combined detection of CD44 and CD133 expression can be an especially effective tool for pathological diagnosis and prognostic prediction of gastric cancer patients in clinical applications.

Expression of CD44 according to Clinicopathologic Characteristics of Gastric Cancer

“…In a meta-analysis of 4,729 patients enrolled in a total of 26 studies utilizing CD44 immunostaining for gastric cancer tissue, CD44 expression was related with intestinal type gastric cancer [25].…”

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

“…Gastric CSCs have been identified in different studies with cell surface molecules namely CD44, CD133, ALDH1, and CD49f [19][20][21][22]. GC cells expressing these markers retain sphere-forming and tumor-initiating activities and some of them, namely CD44 and CD133, also have clinical relevance as markers of poor prognosis [23,24]. Thus, in GC, the identification of CSCs has been largely dependent on the combination of distinct cell surface markers that often differ among tumor types, and whose robustness in distinguishing tumorigenic from non-tumorigenic cells has been increasingly challenged [25][26][27].…”

CD45dimCD34+CD38−CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia

“…The hypothesis that cancer stem cells including LSCs are responsible for the initiation, relapse, and drug resistance of cancers has caused a great deal of excitement in this area of research. The importance of cancer stem cells has been demonstrated in a variety of tumors [6,[25][26][27][28][29]. Especially, LSCs have unlimited capacity of self-renewal and are responsible for the maintenance of leukemia.…”

“…Although the precise function of CD133 remains unknown, it is associated with aggressive cancers and poor prognosis. CD133 is known to be required for tumor growth and survival [14,29,32]. Fig.…”