The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases

Abstract

Abstract. Background Colon cancer has a yearly incidence of 43 per 100,000 inhabitants in Sweden (1). Within 3 years after the diagnosis of colorectal cancer, 29% of patients will have developed liver metastases (2). In case these can be resected, 5-year survival of up to 60% is achievable (3).Prognostic factors have been identified over time and several predictive models have been created for the stratification of patients into risk categories in order to select management strategies and predict prognosis (4).Cancer stem cells (CSCs) represent a subset of cancer cells that are presumed to have the properties of normal adult stem cells. These characteristics include the capacity of selfrenewal and asymmetric division, multipotency for differentiation, as well as relatively long cycling times and long-term survival. Research has shown CSCs to be a source of tumour recurrence and resistance to chemotherapy (5). The most often used technique for the identification of CSCs is through the selection of a subpopulation of tumour cells based on the expression of certain cell surface markers (6). Examples of such markers in colorectal cancer are cluster of differentiation (CD) markers CD44, CD133 and CD24 (7-9). CD44 is a cell surface glycoprotein, known to be involved in cell growth, differentiation, adhesion and survival (10). CD133 is a transmembrane glycoprotein, localised mainly at the level of membrane protrusions (11). CD24 is a heavily glycosylated cell surface protein, thought to have various functions in proliferation and cell adhesion (12). In colorectal cancer patients, CD44 and CD24 have been associated with decreased OS (13, 14), whilst a metaanalysis showed that CD133 is correlated with a worsened OS and DFS (15). Studies regarding the expression of these markers in colonic liver metastases and its influence on survival after hepatectomy are sparse (16)(17)(18). The aim of this study was to assess the expression of CD44, CD133 and CD24 in colon cancer liver metastases and to analyse their predictive value for OS and DFS after liver resection. Materials and MethodsPatients. All consecutive cases of liver resection for colon cancer metastases at Skåne University Hospital, in both Lund and Malmö, Sweden, between January 2006 and December 2014, were identified. From these, patients who also were operated for their primary colon cancer at these hospitals were included in this retrospective cohort study. No patients with rectal cancer were included. Only patients with adenocarcinoma were included, whilst patients with other tumour types, such as mucinous cancers, were excluded.

CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance

“…HCC is also associated with a high mortality because of its prolific rate of recurrence and heterogeneity, which has been attributed to the existence of cancer stem cells (CSCs) 5 . The proliferation and differentiation capabilities of liver CSCs are believed to be responsible for tumor initiation, progression, relapse, metastasis and resistance to therapy 6 , 7 . For this reason, CSCs and their associated pathways are becoming the focus of potential therapies for HCC.…”

Immunohistochemical investigation of prognostic biomarkers in resected colorectal liver metastases: a systematic review and meta-analysis

“…Lack of CD133 expression was identified as an independent marker for decreased OS after resection of CRLM [91]. One study found an insignificant trend towards CD133-expression and decreased OS after liver resection, although a significant association between CD133 status on disease-free survival was found [92]. Approximately 60% of CRLM lesions have been found to stain positive for CD133 [91].…”

The Potential Role of CD44 and CD133 in Colorectal Stem Cell Cancer

“…Xia et al (2016) and Spelt et al (2018) illustrated that CD44 is one of the promising markers that will effectively assess the prognosis for colorectal CSCs [ 38 , 39 ]. Ozawa et al (2014) found positive CD44 alone showed poor survival overall.…”