The study identifies MMP10 as a novel candidate biomarker to help accurately identify those likely to develop cancer metastases.
(Dr. Amit Dutt with his team members, Image Credit: Dr. Amit Dutt)
Tobacco-associated cancer of the lung, head, and neck forms about 40% of all cancers observed in India. In spite of such alarming increase, effective development of targeted therapeutics remains at large - due to lack of our understanding of the molecular changes that drive the formation of tumours in these cancers.
In a study published in the “Oral Oncology”- an official journal of the European Association of Oral Medicine, International Association of Oral Pathologists, Dr. Amit Dutt (Shanti Swarup Bhatnagar Prize (SSB) for Science and Technology 2017 in Medical Sciences), Wellcome Trust/ DBT India Alliance Int. Fellow, Tata Memorial Centre-ACTREC, and his team present a comprehensive landscape of genetic alterations that underlie an early stage tongue tumors. Their study led to the identification of a gene, Matrix Metalloproteinase (MMP10), as a potential prognostic biomarker to identify those likely to develop cancer metastases- i.e. spread of cancer from one organ to another from an early on stage.
In this study, total 57 patients were studied. Majority of the patients were in an early stage of tongue tumors with tobacco/nut chewing habits. High-throughput genomics and computational analysis were performed to identify MMP10 as a potential biomarker in these patients. "Integrative genomics analysis revealed that about 50 % of the patients indicated altered expression of MMP10 gene," says Dr. Pratik Chandrani, one of the authors and a post-doctoral researcher.
During the examination of patients by doctors, the presence of regional lymph node metastasis, if so any, plays a conclusive role in the choice of treatment. About 70% of patients with early T1 or T2 stage tumours may not harbor any nodal metastasis in the neck. This study identifies MMP10 as a novel candidate biomarker to help accurately identify these 70% patients, who could thus be spared from unnecessary surgery with known harmful effects.
“I anticipate the outcome of validated novel therapeutic targets from this study to profoundly inform the designing of successful clinical trials,” said Dr. Amit Dutt.
In spite of all the technological developments in radiology, preoperative estimation of metastatic nodal status among early tongue cancer patient is highly inaccurate. Therefore, routine physical neck dissection and conventional pathological estimation of the entire dissected nodes still remains the gold standard in staging neck nodal status in patients with tongue cancers.
“Accurate prediction of metastases in tongue cancers— as MMP10 expression level appears as a promising candidate-- would have an immediate clinical impact through avoidance of unnecessary treatment of patients at low risk with appropriate direction of resources toward aggressive treatment of patients at high risk of having metastatic disease,” said Dr. Sudhir Nair (Clinician Scientist - Head & Neck).
“The finding from our study provides a roadmap to validate the MMP10 as a potential prognostic biomarker to stratify those likely to develop metastases in tongue cancer patients. However, further clinical and functional validation in a large number of patient and cells would be required,” said Dr. Pawan Upadhyay, first author of this paper.