The Prognostic Value of Cancer Stem Cell Markers (Notch1, ALDH1, and CD44) in Primary Colorectal Carcinoma

Mohamed, Salem Youssef; Kaf, Randa Mohamed; Ahmed, Mona M.; Elwan, Amira; Ashour, Hassan; Ibrahim, Amr

doi:10.1007/s12029-018-0156-6

Cited by 41 publications

(36 citation statements)

References 34 publications

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“…High ALDH activity has been shown to support clonogenic property in CRC cells and generate cells with enhanced stem cell properties [36]. In addition, elevated ALDH levels in CRC patients has a strong association with inferior prognosis [37]. In our study, knockdown of OPN restricted the ALDH1 high CSCs ratio, which suggests that OPN is implicated in the “stemness” of CRC cells.…”

Section: Discussionsupporting

confidence: 53%

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

et al. 2019

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Background Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved. Material/Methods Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3β-β/catenin pathway was detected by western blot. Results OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3β-β/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. Conclusions OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3β-β/catenin pathway.

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Section: Discussionsupporting

confidence: 53%

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

et al. 2019

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“…Of these studies, 30 studies that evaluated the prognostic role of CD44 in CRC patients were in accordance with the inclusion criteria (24–28, 34–57, 66). Thirty four studies reported the association of CD44 expression with clinicopathological features (24, 26, 27, 35, 39–42, 44, 46, 47, 49, 52, 54, 57, 67–84).…”

Section: Resultsmentioning

confidence: 99%

The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis

et al. 2019

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Background: CD44 is widely used as a putative cancer stem cells (CSCs) marker for colorectal cancer (CRC). However, the prognostic role of CD44 in CRC remains controversial. Methods: We performed a systematic review and meta-analysis to evaluate the association of various CD44 isoforms and overall survival (OS) and clinicopathological features of CRC patients. Results: A total of 48 studies were included in the meta-analysis. Total CD44 isoforms overexpression was significantly correlated with worse OS of patients with CRC (HR = 1.32, 95% CI = 1.08–1.61, P = 0.007). In a stratified analysis, a higher level of either CD44v6 or CD44v2 had an unfavorable impact on OS (HR CD44v6 = 1.50, 95% CI = 1.10–2.14, P = 0.010; HR CD44v2 = 2.93, 95% CI = 1.49–5.77, P = 0.002). Additionally, CD44 was shown to be associated with some clinicopathological features, such as lymph node metastasis (OR CD44 = 1.56, 95% CI = 1.01–2.41, P = 0.044; OR CD44v6 = 1.97, 95% CI = 1.19–3.26, P = 0.008; OR Total CD44 isoforms = 1.57, 95% CI = 1.15–2.14, P = 0.004), distant metastasis (OR CD44 = 2.90, 95% CI = 1.08–7.83, P = 0.035; OR Total CD44 isoforms = 1.89, 95% CI = 1.02–3.53, P = 0.044). Moreover, a high level of CD44 showed a possible correlation with poor differentiation (OR Total CD44 isoforms = 1.44, 95% CI = 1.00–2.08, P = 0.051), elevated level of CD44v6 tend to be correlated with tumor size (OR = 1.71, 95% CI = 0.99–2.96, P = 0.056). Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis.

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“…ALDH1 expression is associated with colon cancer location [73], with advanced stages of the disease [75], with number of lymph nodes involved (N) [73,75,76], and with perivenous invasion (V) [73] but also with local tumor recurrence [75]. The association between ALDH1 expression and lymph node involvement was not seen by Zhou et al [74].…”

Section: Author Detailsmentioning

confidence: 99%

“…Recently, ALDH1 expression was found to be involved in epithelial-mesenchymal transition (EMT) and could play, thus, a role in cancer progression and distant metastases formation [75][76][77].…”

Section: Author Detailsmentioning

confidence: 99%

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Stem Cell Markers in Colon Cancer

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2019

Basic Principles and Practice in Surgery

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Colon cancer incidence is increasing in young people. Even if, so far, colon cancer had a maximum incidence in the sixth and seventh decades of life, lately its incidence in people age 50 and younger is increasing. Thus, colon cancer still represents a major health problem despite constant research made in the field. Early detection of colon cancer is mandatory for an appropriate treatment of the disease and to attain increased overall survival. Even if various stem cell markers have been studied in order to evaluate their prognostic value in colon cancer cases, results in literature are heterogeneous, and no clear consensus has been drafted so far. This paper aims to review the most important stem cell markers identified in colon cancer and to establish their role in both cancer diagnosis and progression.

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The Prognostic Value of Cancer Stem Cell Markers (Notch1, ALDH1, and CD44) in Primary Colorectal Carcinoma

Abstract: Expression of stem cell markers ALDH1, Notch1, and CD44 correlates with poor prognosis in a CRC and represents an independent prognostic factor. They are associated with a feature of epithelial-mesenchymal transition evidenced by their association with high tumor burden.

Cited by 41 publications

References 34 publications

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis

Stem Cell Markers in Colon Cancer

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