Clinicopathological significance of non-small cell lung cancer with high prevalence of Oct-4 tumor cells.
BACKGROUND
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.


METHODS
We 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.


RESULTS
Oct-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.


CONCLUSIONS
Our 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.
Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Lung Cancer Research Center of Sun Yat-sen University, Guangzhou, Guangdong, China. chenzhenguang@yahoo.com
Zhenguang
Z
Chen
Tao
T
Wang
Lie
L
Cai
Chunhua
C
Su
Beilong
B
Zhong
Yiyan
Y
Lei
Andy Peng
AP
Xiang
D000230:Adenocarcinoma / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D019394:Ki-67 Antigen; D050814:Octamer Transcription Factor-3; D042461:Vascular Endothelial Growth Factor A