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


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.


CONCLUSIONS
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.
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.
Sharada
S
Sawant
Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
Ravindran
R
Gokulan
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Harsh
H
Dongre
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Milind
M
Vaidya
Head and Neck Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
Devendra
D
Chaukar
Medical Oncology Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
Kumar
K
Prabhash
Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Arvind
A
Ingle
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Shriya
S
Joshi
Sarin Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Prerana
P
Dange
Department of Biology, University of Kentucky, 101 TH Morgan Building, Lexington, KY, 40506, USA.
Shreyas
S
Joshi
Vaidya Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, Maharashtra, India.
Archana Kumari
AK
Singh
Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Govindpura 462023, Bhopal, Madhya Pradesh, India.
Vidhi
V
Makani
Head and Neck Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
Shilpi
S
Sharma
Microbiology Laboratory, 12A, Cowley Brown Road (East), R.S. Puram, Coimbatore, 641 002, Tamilnadu, India.
Ashok
A
Jeyaram
Pathology Department, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
Shubhada
S
Kane
Head and Neck Unit, Tata Memorial Hospital (TMH), Parel, Mumbai, 400 012, India.
Anil
A
D'Cruz
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009364:Neoplasm Recurrence, Local; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011379:Prognosis; D055291:Salivary alpha-Amylases / Q000378:metabolism*; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C476399:Cd44 protein, mouse; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; C116115:MYCBP protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors; C524799:Amy1 protein, mouse; D055291:Salivary alpha-Amylases
CD44; Cancer stem cells; Oct4; Oral cancer; Prognosis; Recurrence