Tata Memorial develops novel biomarker for tongue cancer spread to spare 70% patients from neck surgery
Tongue cancer is relatively common, accounting for about 47 per cent of all oral cancer cases in young people. Tata Memorial team finds protein that can help detect metastasis early and save patients from excision surgery and death
The research team Low accuracy in detecting its spread in the early stages is one of the factors that contributes to the high incidence of tongue cancer in India. About 30 per cent of tongue cancer patients develop occult (hidden) metastases or a subclinical disease spread to surrounding lymph nodes. This reduces their chances of survival.
Researchers from the Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre (TMC), have been able to identify a predictive biomarker for early stage disease. They found that a protein called Matrix metalloproteinase-10 (MMP10) is over-expressed in primary tongue tumours of patients with lymph node metastases. This means that measuring MMP10 expression could be used to predict the likelihood of lymph node metastases in these patients. The study findings have been published recently in Communications Biology, a Nature publications group journal.
“We propose that screening for the expression of MMP10 could help as a prognostic biomarker in the prediction of lymph node metastases in tongue cancer, sparing 70 to 80 per cent of patients from morbid neck dissection and surgical removal of lymph nodes. These findings may enhance treatment and prognosis,” says Dr Amit Dutt, Principal Investigator, ACTREC Tata Memorial Centre and lead researcher of the study.
Researchers at the Tata Memorial Centre in Mumbai are in the process of planning a clinical trial to validate the findings. “The leads from this study can help the treating team to decide on the best course of therapy,” says Dr Sudhir Nair, a senior oral cancer surgeon at TMC and lead researcher of the study. “An early detection of MMP10 in oral samples, such as saliva or oral mucosa, could indicate the presence of a disease or condition in its early stages. If validated this can be used as part of an oral screening programme to help detect diseases or conditions early on, when they are most likely to be treatable,” he adds.
Currently treatment options for oral cancer may include surgery, radiation therapy, chemotherapy, and targeted therapy. “Tongue cancer is a type of oral cancer that forms in the front two-thirds of the tongue. It is relatively common, accounting for about 47 per cent of all oral cancer cases in young people,” Dr Dutt says.
This surgical removal of lymph nodes is linked with severe morbidity and is unnecessary in about 70 per cent of patients without nodal metastases, say researchers and hence underline the importance of precise prognostic indicators to predict the probability of metastases.
Currently, the risk for nodal metastases is assessed by physical examination such as size, location, histological type, lymphovascular invasion, severity of the initial tumour as well as imaging tests like CT or MRI scans. But these techniques are unreliable. “The MMP10 expression accurately predicts lymph node metastases in 86 per cent of node-positive patients,” says Bhasker Dharavath, first author of the study.
He adds that researchers have identified a microRNA, miR-944, that negatively affects the levels of MMP10 by directly binding to the regulatory region of the gene and interfering with its molecular processing. Using biochemical and cell-based research, the group also showed that low levels of MMP10 protein or higher expression levels of miR-944 inhibit the proliferation, migration and dissemination of tongue cancer cells. Dr Ashwin Butle constructed a complex orthotopic tongue cancer mouse model to validate the findings.
