Sharada Sawant1, Ravindran Gokulan2, Harsh Dongre3, Milind Vaidya3, Devendra Chaukar4, Kumar Prabhash5, Arvind Ingle6, Shriya Joshi3, Prerana Dange7, Shreyas Joshi8, Archana Kumari Singh3, Vidhi Makani9, Shilpi Sharma4, Ashok Jeyaram10, Shubhada Kane11, Anil D'Cruz4. 1. Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India. sssawant@actrec.gov.in. 2. Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. 3. Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India. 4. Head and Neck Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India. 5. Medical Oncology Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India. 6. Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India. 7. Sarin Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India. 8. Department of Biology, University of Kentucky, 101 TH Morgan Building, Lexington, KY, 40506, USA. 9. Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Govindpura 462023, Bhopal, Madhya Pradesh, India. 10. Microbiology Laboratory, 12A, Cowley Brown Road (East), R.S. Puram, Coimbatore, 641 002, Tamilnadu, India. 11. Pathology Department, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
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.
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 immunodeficientmice. 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 cancerpatients. In addition, these molecules may find use as molecular targets for effective therapy.
Entities:
Keywords:
CD44; Cancer stem cells; Oct4; Oral cancer; Prognosis; Recurrence
Authors: A Kosunen; R Pirinen; K Ropponen; M Pukkila; J Kellokoski; J Virtaniemi; R Sironen; M Juhola; E Kumpulainen; R Johansson; J Nuutinen; V-M Kosma Journal: Oral Oncol Date: 2006-06-23 Impact factor: 5.337
Authors: Adriana S Beltran; Ashley G Rivenbark; Bryan T Richardson; Xinni Yuan; Haili Quian; John P Hunt; Eric Zimmerman; Lee M Graves; Pilar Blancafort Journal: Breast Cancer Res Date: 2011-09-27 Impact factor: 6.466
Authors: Adriana A Marin; Oscar Murillo; Rodrigo A Sussmann; Luana S Ortolan; Daniella S Battagello; Thatyane de Castro Quirino; Jackson C Bittencourt; Sabrina Epiphanio; Alejandro M Katzin; Leonardo J M Carvalho Journal: Antimicrob Agents Chemother Date: 2021-03-01 Impact factor: 5.191
Authors: Eduardo Alonso Cruz Monroy; Pedro Paulo de Andrade Santos; Maria Luiza Diniz de Sousa Lopes; Adalberto Mosqueda-Taylor; Leão Pereira Pinto; Lélia Batista de Souza Journal: Histochem Cell Biol Date: 2018-07-03 Impact factor: 4.304
Authors: Helen H Yu; Therese Featherston; Swee T Tan; Alice M Chibnall; Helen D Brasch; Paul F Davis; Tinte Itinteang Journal: Front Surg Date: 2016-08-02