Cancer stem cells in human digestive tract malignancies

Rassouli, Fatemeh Behnam; Matin, Maryam Moghaddam; Saeinasab, Morvarid

doi:10.1007/s13277-015-4155-y

Cited by 50 publications

(40 citation statements)

References 247 publications

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“…The specificity and robustness of CD133 as a colorectal CSC marker may also need further investigation (36,37). The combinatorial use of other markers, such as CD44 and ALDH1, in colorectal cancers may better clarify CSC features and how p53 may affect stem cell characteristics of colorectal cancer (38).…”

Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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Abstract. Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53 IntroductionColorectal carcinoma (CRC), which is prone to metastasis and recurrence, is a cancer with a high lethality rate worldwide. More than 50% of patients will develop metastasis and recurrence (1,2). Multiple factors account for metastasis and recurrence, including tumor stage, cancer subtypes and cancer stem cells (CSCs). CSCs are a small population of tumor-initiating cells that have the ability to self-renew and differentiate in tumors in vivo. CSCs are involved in various processes during tumor formation, progression, and angiogenesis and are considered an important target for novel cancer treatment strategies (3). Several specific surface markers are expressed on CSCs, including CD133, CD44 and aldehyde dehydrogenase 1 (ALDH1) (4). CD133 (also known as prominin-1) is a 5-transmembrane glycoprotein of 865 amino acids with a total molecular weight of 120 kDa. CD133 is a CSC marker in colon carcinoma. CD133-positive cells correlate strongly with poor prognosis and synchronous liver metastasis (5). Cancer cell populations with high expression of CD133 are much more aggressive in terms of metastases compared with those with low expression of CD133, suggesting that CD133 may be a marker of increased tumorigenesis ability. CD133-positive cells from clinical biopsy-derived cultures have been demonstrated to possess multilineage differentiation potential and are capable of tumor initiation in vivo. CD133-positive CRC cells are more resistant to chemoradiotherapy, and CD133 expression is associated with poor prognosis (6,7). However, the regulation of CD133 expression has not been fully elucidated.The present study demonstrated that CD133 expression was associated with the tumor protein p53 (p53) expression in an HCT116 p53 +/+ cell line. Of note, CD133-negative cells were detected in the colon cancer cell line HCT116 in a previous report by Kai et al (8

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Section: Discussionmentioning

confidence: 99%

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

et al. 2018

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“…Significantly, among these genes are prominent markers of cancer stem cells, including CD24, PROM1 (or CD133), and EPCAM, all of which are associated with cancer “stemness” in gastrointestinal tumors. 29,30 This suggests that the unfavorable AC subtype might be driven, in part, by a stem cell-like phenotype. Indeed, this hypothesis is supported by the GSEA finding (Fig.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix

Levine

Votanopoulos

Qasem

et al. 2016

Journal of the American College of Surgeons

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BACKGROUND Appendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. STUDY DESIGN Gene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes. RESULTS Unsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease-specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low-grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age. CONCLUSIONS The 139-gene cassette can have actionable clinical utility for identifying low-grade appendiceal tumor molecular subtypes predictive of therapeutic efficacy of CRS/HIPEC.

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“…Recently, some studies have suggested that CSCs are closely related to tumor progression, metastasis, and processes of treatment resistance in GC [58]. Notably, recent research has demonstrated that CD44-positive tumor cells posses CSC properties, such as self-renewal and tumorigenicity, and the presence of CSCs is typically regarded as a marker of poor prognosis in patients with GC [59].…”

Section: Discussionmentioning

confidence: 99%

CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies

Fang

Lai³

et al. 2016

Cell Physiol Biochem

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Background/Aims: The prognostic power of the levels of total CD44 and its isoform CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore, our study aims to generalize the clinicopathological and prognostic significance of these two proteins in GC. Methods: A literature search of the PubMed, Web of Science and Embase databases was conducted to identify eligible studies. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess the effects. Results: In all, 42 studies including 6,229 patients were included in this analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44 was positively correlated with the T category, the N category, distant metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44 overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI = 1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to those for total CD44. However, total CD44 or CD44v6 expression was not correlated with tumor size and histological grade. Conclusion: High CD44 or CD44v6 expression levels were correlated with cancer progression and poor prognosis in patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic biomarkers for GC.

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Cancer stem cells in human digestive tract malignancies

Cited by 50 publications

References 247 publications

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

p53 positively regulates the expression of cancer stem cell marker CD133 in HCT116 colon cancer cells

Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix

CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies

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