Abstract

BackgroundExpression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non-small cell lung cancer (NSCLC) and investigate its possible molecular mechanism.MethodsWe measured Oct-4 expression in 113 NSCLC tissue samples and three cell lines by immunohistochemical staining and RT-PCR. The association of Oct-4 expression with demographic characteristics, proliferative marker Ki67, microvessel density (MVD), and expression of vascular endothelial growth factor (VEGF) were assessed.ResultsOct-4 expression was detected in 90.3% of samples and was positively correlated with poor differentiation and adenocarcinoma histology, and Oct-4 mRNA was found in each cell lines detected. Overexpression of Oct-4 had a strong association with cells proliferation in all cases, MVD-negative, and VEGF-negative subsets. A Kaplan-Meier analysis showed that overexpression of Oct-4 was associated with shorter overall survival in all cases, adenocarcinoma, squamous cell carcinoma, MVD-negative, and VEGF-negative subsets. A multivariate analysis demonstrated that Oct-4 level in tumor tissue was an independent prognostic factor for overall survival in all cases, MVD-negative, and VEGF-negative subsets.ConclusionOur findings suggest that, even in the context of vulnerable MVD status and VEGF expression, overexpression of Oct-4 in tumor tissue represents a prognostic factor in primary NSCLC patients. Oct-4 may maintain NSCLC cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation.

Highlights

  • Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting

  • On the basis of previous reports that a subset of non-small cell lung cancer (NSCLC) tumors do not induce angiogenesis but instead co-opt the normal vasculature for further growth [16,17], we evaluated associations of Oct-4 expression with tumor cell proliferation and prognosis in subsets of patients with weak vascular endothelial growth factor (VEGF)-mediated angiogenesis

  • Our results provide the first demonstration that expression of the stem cell marker Oct-4 maintains tumor cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation

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Summary

Introduction

Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non-small cell lung cancer (NSCLC) and investigate its possible molecular mechanism. Not all patients with lung cancer benefit from routine surgery and chemotherapy. This is especially true for those with. Oct-4 is re-expressed in germ cell tumors [8], breast cancer [9], bladder cancer [10], prostate cancer and hepatomas [11,12], but very little is known about its potential function in malignant disease [13]. Its asymmetric expression may indicate that Oct-4 is a suitable target for therapeutic intervention in adenocarcinoma and bronchioloalveolar carcinoma [15], the role of Oct-4 expression in primary NSCLC has remained ill defined

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