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 Caspa 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

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)43-56
Number of pages14
JournalClinical Oral Investigations
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Cancer stem cells
  • CD44
  • Oct4
  • Oral cancer
  • Prognosis
  • Recurrence

ASJC Scopus subject areas

  • Dentistry(all)

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    Sawant, S., Caspa Gokulan, R., Dongre, H., Vaidya, M., Chaukar, D., Prabhash, K., Ingle, A., Joshi, S., Dange, P., Joshi, S., Singh, A. K., Makani, V., Sharma, S., Jeyaram, A., Kane, S., & D’Cruz, A. (2016). Prognostic role of Oct4, CD44 and c-Myc in radio–chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice. Clinical Oral Investigations, 20(1), 43-56. https://doi.org/10.1007/s00784-015-1476-6