Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma.
BACKGROUND
The interactions between cancer stem cells (CSCs) and tumor-associated macrophages (TAMs) can promote tumor progression, maintain the CSCs population, and reduce therapeutic effects. The objective of this study was to investigate the coexpression of CSCs and TAMs and its clinical significance in pancreatic ductal adenocarcinoma (PDAC).


METHODS
Ninety-six patients with PDAC were included in this study. Tissue microarrays were constructed for immunostaining of the CSCs markers CD44 and CD133 and the TAMs marker CD204. Correlations between the expression of CSCs and TAMs markers and clinicopathologic characteristics or disease progression were analyzed.


RESULTS
Expression levels of CD44/CD133 and CD204 were significantly higher in tumor tissues than in normal tissues (P < .0001). The variables associated with survival were high coexpression of CD44/CD133 (P = .000), high expression of CD204 (P = .011), and tumor grade (P = .014). There was a positive correlation between CD44/CD133 and CD204 expression (r = 0.294; P = .004). Survival analysis indicated that high coexpression of CD44/CD133 and CD204 was associated significantly with shorter overall survival (P = .000) and disease-free survival (P = .003). Multivariate analysis revealed that high CD44/CD133 expression was an independent prognostic factor for disease-free survival, whereas high CD204 expression was an independent predictor for both overall and disease-free survival.


CONCLUSIONS
Coexpression of CD44/CD133 and CD204 is a useful survival prediction marker for patients with PDAC.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Ya-Chin
YC
Hou
Ying-Jui
YJ
Chao
Hui-Ling
HL
Tung
Hao-Chen
HC
Wang
Yan-Shen
YS
Shan
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002450:Cell Communication; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D051117:Scavenger Receptors, Class A / Q000378:metabolism*
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C495139:MSR1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D051117:Scavenger Receptors, Class A
CD133; CD204; CD44; cancer stem cells; pancreatic ductal adenocarcinoma; tissue microarrays; tumor-associated macrophages