Putative stem cell markers in cervical squamous cell carcinoma are correlated with poor clinical outcome

BMC Cancer. 2015 Oct 24:15:785. doi: 10.1186/s12885-015-1826-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldehyde Dehydrogenase 1 Family
  • Biomarkers, Tumor / biosynthesis*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Female
  • Humans
  • Integrin alpha6 / biosynthesis
  • Isoenzymes / biosynthesis
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Nerve Tissue Proteins / biosynthesis
  • Prognosis
  • RNA-Binding Proteins / biosynthesis
  • Retinal Dehydrogenase / biosynthesis
  • SOXB1 Transcription Factors / biosynthesis
  • Survival Rate / trends
  • Treatment Outcome
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • Integrin alpha6
  • Isoenzymes
  • MSI1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase