CD133 mRNA expression and microsatellite instability in colorectal carcinoma

Huh, Jung Wook; Park, Yeon Sun; Lee, Jae Hyuk; Kim, Hyeong Rok; Shin, Myung Geun; Kim, Young Jin

doi:10.1002/jso.21734

Cited by 22 publications

(25 citation statements)

References 25 publications

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“…4,37,38,40 In contrast, according to other investigators, CD133 overexpression was unassociated with tumor progression 40,41 or survival rate 17 and was not an independent risk factor for recurrence. 17,36,39 In 2 patient series, CD44 expression correlated with neither clinicopathological features nor long-term outcomes. 17,41 To date, no previous data were available on the combined analysis of these 2 markers.…”

Section: /Cd44mentioning

confidence: 94%

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Combined CD133/CD44 Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer

Galizia¹

2012

Arch Surg

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Because of some inconsistencies in the traditional model of human colorectal carcinogenesis, the cancer stem cell (CSC) model was recently proposed, in which tumor results from neoplastic transformation of stem cells, which become CSCs. Identification of CSCs by expression of surface antigens remains a critical issue because no biomarker has been shown to be completely reliable. CD133 and CD44 are commonly used as CSC markers, and correlation of their expression with colorectal cancer (CRC) clinicopathological features and outcomes may be useful.

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Section: /Cd44mentioning

confidence: 94%

“…39 In the present study, we aimed to overcome these discrepancies by using flow cytometry, which allowed more accurate identification of tumor cells and avoidance of arbitrary cutoff values. When necessary, ROC curve analysis was applied to identify the best cutoff value.…”

Section: /Cd44mentioning

confidence: 99%

Combined CD133/CD44 Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer

Galizia¹

2012

Arch Surg

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“…1). Mutations in signaling pathways are used as markers for predicting prognosis, but also expression levels of proteins that are suggested to identify the cancer stem cell (CSC) fraction of the tumor (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). CSCs, the driving force behind tumor initiation, growth, and metastasis, are hypothesized to be crucial for patient prognosis.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the Ras–Raf Axis Underlie the Prognostic Value of CD133 in Colorectal Cancer

Kemper

Versloot

Cameron

et al. 2012

Clinical Cancer Research

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Purpose: High expression of cancer stem cell (CSC) marker CD133 has been used as a predictor for prognosis in colorectal cancer (CRC), suggesting that enumeration of CSCs, using CD133, is predictive for disease progression. However, we showed recently that both CD133 mRNA and protein are not downregulated during differentiation of colon CSCs, pointing to an alternative reason for the prognostic value of CD133. We therefore set out to delineate the relation between CD133 expression and prognosis.Experimental Design: A CRC patient series was studied for expression of CD133 and other CSC markers by microarray and quantitative PCR analysis. In addition, several common mutations were analyzed to determine the relation with CD133 expression.Results: CD133 mRNA expression predicted relapse-free survival in our patient series, whereas several other CSC markers could not. Moreover, no correlation was found between expression of other CSC markers and CD133. Interestingly, high CD133 expression was related to mutations in K-Ras and B-Raf, and inhibition of mutant K-Ras or downstream mitogen-activated protein kinase kinase (MEK) signaling decreases CD133 expression. In addition, an activated K-Ras gene expression signature could predict CD133 expression in our patient set as well as data sets of other tumor types.Conclusion: CD133 expression is upregulated in CRC tumors that have a hyperactivated RasRaf-MEK-ERK pathway and is therefore related to mutations in K-Ras or B-Raf. As mutations in either gene have been related to poor prognosis, we conclude that CD133 expression is not indicative for CSC numbers but rather related to the mutation or activity status of the Ras-Raf pathway. Clin Cancer Res; 18(11); 3132-41. Ó2012 AACR.

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“…

We have read the report by Huh et al [1] with interest, which was published in the recent issue of Journal of Surgical Oncology. The authors examined the CD133 expression in colorectal cancer to analyze its relationship with microsatellite instability (MSI) and the clinicopathological factors.

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confidence: 98%

Is CD133 mRNA expression a prognostic factor in colorectal cancer?

Hayama

Watanabe

Iinuma

2011

Journal of Surgical Oncology

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We have read the report by Huh et al. [1] with interest, which was published in the recent issue of Journal of Surgical Oncology. The authors examined the CD133 expression in colorectal cancer to analyze its relationship with microsatellite instability (MSI) and the clinicopathological factors. They examined the CD133 mRNA levels in 61 primary colorectal adenocarcinomas by reverse transcriptasepolymerase chain reaction and showed that a CD133 mRNA expression was significantly associated with the depth of invasion, lymph node involvement, and lymphovascular invasion. Also, they showed that a CD133 expression was significantly correlated with the MSI status. In survival analysis, the 5-year disease-free survival rate of patients with a low CD133 mRNA expression was significantly higher than that of those patients with high levels of CD133 mRNA expression. Therefore, they concluded that elevated CD133 mRNA levels represent more aggressive tumor biology and poorer survival in patients with colorectal cancer, correlating with a high level of MSI status. We agree that evaluation of mRNA expression in search for prognostic factor is useful and cost-effective in clinical practice instead of other modalities focusing on thousands of genes such as microarray. In fact, we have also reported that the detection of CEA mRNA in peritoneal washings is a useful, rapid genetic diagnosis for the prediction of peritoneal recurrence and survival in patients with colorectal cancer [2]. However, in Huh's study, there is a major issue that needs to be discussed before drawing their conclusion.As Huh et al. stated in their report, there was a significant association between CD133 mRNA expression and the depth of invasion, lymph node involvement, and lymphovascular invasion.And lymphovascular invasion and perineural invasion were the only significant factor for survival by multivariate analysis. Furthermore, as the authors stated, a CD133 mRNA expression was not an independent predictor of disease-free survival on the multivariate analysis. These results do not seem to give rationale to conclude that CD133 mRNA levels represent more aggressive tumor biology and poorer survival in patients with colorectal cancer. Another important issue is the MSI status of the patients. MSI is a well-known prognostic marker in patients with colon cancer. We have also previously shown that MSI patients show better prognosis than patients without MSI in high-risk stage II and stage III colon cancer patients [3]. However, Huh et al. did not include MSI status in either univariate or multivariate analysis of risk factors for survival. We believe they need to evaluate each factor at least on univariate analysis by including MSI status.Although Huh's study presented important findings, we believe these issues need to be addressed sufficiently in order to draw their conclusion.

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CD133 mRNA expression and microsatellite instability in colorectal carcinoma

Abstract: Elevated CD133 mRNA levels may represent more aggressive tumor biology and poorer survival in patients with colorectal cancer, correlating with a high level of MSI status. Larger prospective studies are required to confirm these findings.

Cited by 22 publications

References 25 publications

Combined CD133/CD44 Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer

Combined CD133/CD44 Expression as a Prognostic Indicator of Disease-Free Survival in Patients With Colorectal Cancer

Mutations in the Ras–Raf Axis Underlie the Prognostic Value of CD133 in Colorectal Cancer

Is CD133 mRNA expression a prognostic factor in colorectal cancer?

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