Clinical significance of putative cancer stem cell marker CD44 in different histological subtypes of lung cancer

Cancer Biomark. 2014;14(6):457-67. doi: 10.3233/CBM-140424.

Abstract

Background: According to the cancer stem cell theory, tumors originate from a subset of cells known as cancer stem cells (CSCs) that are responsible for tumor initiation, resistance and relapse. CD44 is a cell adhesion molecule that can aid in the identification of CSCs in various malignancies.

Objective: The purpose of the current study is to evaluate the expression level and clinical significance of CD44 in lung cancer samples.

Methods: One hundred and ninety-five lung tumor samples including 74 (38%) squamous cell carcinomas (SCC), 61 (31%) adenocarcinomas (ADC), 23 (12%) large cell carcinoma (LCC) in non-small cell lung cancer (NSCLC) group and 37 (19%) small cell lung cancer (SCLC) samples were examined for the expression of CD44 using immunohistochemistry method. The correlation of CD44 expression with clinicopathological parameters as well as Ki-67 status was also assessed.

Results: Univariate analysis demonstrated that CD44 expression was significantly higher in NSCLC compared to SCLC (P < 0.001). Among NSCLC, higher level of CD44 expression was found in SCC compared to ADC (P< 0.001) and LCC (P=0.046). Increased expression of CD44 was significantly correlated with higher grade tumors which correspond to poor prognosis in SCC (P=0.012) and the lower level of CD44 expression was more often found in well differentiated ADC tumors (P=0.03). In addition, high expression of CD44 was significantly associated with decreased level of proliferative marker Ki-67 (P=0.04).

Conclusions: CD44 could be a valuable tool for the study of lung CSCs and provide a novel therapeutic target for treatment of the patients with lung cancer in combination with conventional therapy.

Keywords: CD44; Cancer stem cells; Ki-67; non-small cell lung cancer; small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / biosynthesis*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / pathology
  • Small Cell Lung Carcinoma / blood*
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / pathology

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors