Expression and prognostic value of tumor stem cell markers ALDH1 and CD133 in colorectal carcinoma

Abstract

The identification of cancer stem cells (CSCs) has improved the understanding of tumor occurrence and development. According to CSC theory, colorectal carcinoma (CRC) may be derived from these few cells. Thus, markers for CSCs may lead to the identification of CSCs and investigation of the correlation with various clinicopathological features and survival time in human CRC patients. Aldehyde dehydrogenase 1 (ALDH1) and CD133 (also known as Prominin-1 or AC133) were involved in the current study. The aim of the present study was to identify CSCs through markers of CSCs and to explore the value of the CSC markers, ALDH1 and CD133, in human CRC. The correlation between ALDH1 and CD133 protein expression and the various clinicopathological parameters were investigated through immunohistochemistry (IHC). In addition, the Kaplan-Meier method was used to estimate patients’ overall survival. Correlation of the survival differences between ALDH1- or CD133-positive expression and negative controls was analyzed by the log-rank test. Furthermore, the correlation between the expression of ALDH1 and CD133 was assessed by Spearman’s rank correlation. A marked correlation between the differentiation degree and expression of ALDH1 in tumor cells was demonstrated, but not with CD133 expression. In addition, it was demonstrated that low-stage tumors exhibit a higher expression of ALDH1 or CD133 staining compared with high-stage tumors. Meanwhile, CD133 expression was associated with lymph node metastasis-positive cases, but ALDH1 expression was not. Furthermore, compared with negative cases, ALDH1-positive patients exhibited a poor prognosis. However, no significant difference was identified between CD133-positive and -negative cases in terms of survival time. Overall, the results of the present study indicated that ALDH1 and CD133 may serve as useful markers of CSC to predict disease prognosis and clinicopathological characteristics of human CRC.

Clinicopathological Significance of ALDH1A1 in Lung, Colorectal, and Breast Cancers: A Meta-Analysis

“…Accordingly, ALDH1A1 expression may have greater clinical significance in colon cancer than in rectal cancer. Three studies of CRC showed that patients with ALDH1-expressing tumors had shorter survival times than patients with ALDH1-negative tumors [23][24]35]. It therefore appears possible that ALDH1B1 is more important than ALDH1A1 in colorectal cancers.…”

“…Because of its role in the metabolization of reactive acetaldehyde, ALDH1A1 is expressed at high levels in stem cells and regulates stem cell function [12]. However, studies have failed to find associations between ALDH1A1 expression and poor clinical outcomes, and the relationship between ALDH1A1 and clinicopathological features remains controversial [22][23][24][25][26]. ALDH1A1 activity is also increased in stem cell populations in malignant epithelial tumors and cancer cell lines; studies on this topic have often focused on LC, CRC and BC [19][20][21].…”

Isolation, Culture and Identification of Choriocarcinoma Stem-Like Cells from the Human Choriocarcinoma Cell-Line JEG-3

“…CD133 is a trans-membrane glycoprotein, the cell-surface expression of which is down-regulated during differentiation [24]. It has been used widely as a marker for CSCs in lung [25], colon [26], prostate [27], and endometrial [28] cancers. CD44 is a multifunctional class I transmembrane glycoprotein and specific receptor for hyaluronic acid, promoting migration in normal cells, and is highly expressed in almost every cancer cell in its standard or variant form [29].…”

Stem Cell Markers in Colon Cancer

“…Miana Gabriela Pop Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania *Address all correspondence to: miana_my@yahoo.com was found to be overexpressed in colon adenocarcinoma [73,74]. A number of 75.5-76.5% of colon cancer cases express ALDH1 at tumoral level [73,74].…”