Clinical Oral Investigations

, Volume 20, Issue 1, pp 43–56

Prognostic role of Oct4, CD44 and c-Myc in radio–chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice

  • Sharada Sawant
  • Ravindran Gokulan
  • Harsh Dongre
  • Milind Vaidya
  • Devendra Chaukar
  • Kumar Prabhash
  • Arvind Ingle
  • Shriya Joshi
  • Prerana Dange
  • Shreyas Joshi
  • Archana Kumari Singh
  • Vidhi Makani
  • Shilpi Sharma
  • Ashok Jeyaram
  • Shubhada Kane
  • Anil D’Cruz
Original Article

Abstract

Objective

In the present study, we have investigated the prognostic value of known stem cell-associated molecules such as Oct4, CD44 and c-Myc in patients with oral SCC who had received post-surgery radio- and/or chemotherapy.

Materials and methods

Immunohistochemistry was performed to analyse the expression of Oct4, CD44 and c-Myc in 87 tumour tissues, and the expression profile obtained was correlated with clinicopathological parameters of the patients with oral cancer. Tumourigenic potential of these molecules was also evaluated by in vivo studies.

Results

Our results showed significant correlation of Oct4 (OS, p = 0.003; DFS, p = 0.001) and c-Myc (OS, p = 0.01; DFS, p = 0.03) with overall survival and disease-free survival independently. Furthermore, all the three markers in combinations of two markers each, i.e. Oct4 + CD44 (OS, p = 0.003; DFS, p = 0.001), Oct4 + c-Myc (OS, p = 0.0001; DFS, p = 0.0001), CD44 + c-Myc (OS, p = 0.008; DFS, p = 0.02) and in combinations of three markers each, i.e. Oct4 + CD44 + c-Myc (OS, p = 0.0001; DFS, p = 0.0001) also significantly correlated with overall survival and disease-free survival. Univariate and multivariate analyses further established the independent prognostic value of Oct4. Oct4-, CD44- and c-Myc-enriched populations independently induced sarcomatoid carcinomas whereas primary keratinocytes developed poorly differentiated carcinomas in immunodeficient mice.

Conclusions

Oct4 and c-Myc independently as well as in combination with CD44 might be useful for the prediction of local recurrence and poor survival of patients with oral cancer which is the novel finding of this study.

Clinical relevance

Oct4, c-Myc and CD44 can be used to predict local recurrence and the outcome of treatment in oral cancer patients. In addition, these molecules may find use as molecular targets for effective therapy.

Keywords

Oral cancer Recurrence Cancer stem cells Oct4 CD44 Prognosis 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Sharada Sawant
    • 1
  • Ravindran Gokulan
    • 2
  • Harsh Dongre
    • 1
  • Milind Vaidya
    • 1
  • Devendra Chaukar
    • 3
  • Kumar Prabhash
    • 4
  • Arvind Ingle
    • 5
  • Shriya Joshi
    • 1
  • Prerana Dange
    • 6
  • Shreyas Joshi
    • 7
  • Archana Kumari Singh
    • 1
  • Vidhi Makani
    • 8
  • Shilpi Sharma
    • 9
  • Ashok Jeyaram
    • 10
  • Shubhada Kane
    • 11
  • Anil D’Cruz
    • 9
  1. 1.Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)Tata Memorial CentreNavi MumbaiIndia
  2. 2.Department of Oral Biology and Biomedical Sciences, Faculty of DentistryUniversity of MalayaKuala LumpurMalaysia
  3. 3.Head and Neck UnitTata Memorial Hospital (TMH)MumbaiIndia
  4. 4.Medical Oncology UnitTata Memorial Hospital (TMH)MumbaiIndia
  5. 5.Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)Tata Memorial CentreNavi MumbaiIndia
  6. 6.Sarin Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC)Tata Memorial CentreNavi MumbaiIndia
  7. 7.Department of BiologyUniversity of KentuckyLexingtonUSA
  8. 8.Laboratory of Chromatin Biology, Department of Biological SciencesIndian Institute of Science Education and ResearchBhopalIndia
  9. 9.Head and Neck UnitTata Memorial Hospital (TMH)MumbaiIndia
  10. 10.Microbiology LaboratoryCoimbatoreIndia
  11. 11.Pathology DepartmentTata Memorial Hospital (TMH)MumbaiIndia

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