Putative stem cell markers in cervical squamous cell carcinoma are correlated with poor clinical outcome.
BACKGROUND
The aim of this study was to elucidate the value of putative cancer stem cell markers Musashi-1, ALDH1, Sox2, and CD49f in predicting the prognosis in cervical squamous cell carcinoma (CSCC).


METHODS
Real-time PCR and immunohistochemistry staining was performed to examine Musashi-1, ALDH1, Sox2, and CD49f expression in archived specimens of CSCC patients with postoperative chemotherapy. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of CSC markers for overall survival (OS) and recurrent-free survival (RFS).


RESULTS
The Real-time PCR data showed that the expression of all markers were increased in CSCC tissues compared with in paired normal cervical tissues (P < 0.05). The IHC result showed that high expression of Msi1, ALDH1, Sox2, and CD49f was found in 25.7%, 43.0%, 62.0% and 29.0% CSCC samples, respectively. Moreover, high expression of Msi1 (P = 0.033 and P = 0.003, respectively), ALDH1 (P = 0.015 and P = 0.002, respectively), and Sox2 (P = 0.005 and P = 0.003, respectively), and low expression of CD49f (P = 0.027 and P = 0.025, respectively) were correlated with poor OS and PFS in CSCC patients. Interestingly, tumors with Msi1(high)/CD49f(low) expression had the poorest prognosis according to Msi1/CD49f stratification. In multivariate Cox regression analysis, Sox2 expression (P = 0.047 and P = 0.018, respectively), ALDH1 expression (P = 0.013 and P = 0.003, respectively), and CD49f expression (P = 0.008 and P = 0.003, respectively) were independent prognostic markers for both OS and RFS.


CONCLUSIONS
Our results suggest that cancer stem cell markers are linked with poor prognosis of CSCC patients.
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. 1aiyan@163.com.|Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HB, 430022, China. 1aiyan@163.com.
Teng
T
Hou
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. zhanghwgynecol@126.com.
Weijing
W
Zhang
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. tongcj2011@126.com.
Chongjie
C
Tong
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HB, 430022, China. galiaz2@yahoo.fr.
Gallina
G
Kazobinka
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. huangxin02@sina.com.
Xin
X
Huang
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. huangyongw@gmail.com.
Yongwen
Y
Huang
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China. zhangyannapds@126.com.
Yanna
Y
Zhang
D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D039503:Integrin alpha6 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D050697:Retinal Dehydrogenase / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality
D014408:Biomarkers, Tumor; D039503:Integrin alpha6; D007527:Isoenzymes; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase