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Cancer: How to identify high-risk patients?

A poor prognosis subtype of HNSCC is consistently observed across methylome, transcriptome, and miRNome analysis.

Jung AC, Job S, Ledrappier S, Macabre C, Abecassis J, de Reyniès A, Wasylyk B.

Clin Cancer Res Aug. 1, 2013


June 24, 2013

Bohdan Wasylyk’s team at the IGBMC, in collaboration with Dr. Alain Jung from the Centre Paul Strauss (Centre de Lutte contre le Cancer) Strasbourg, and the bioinformatics team of the Cartes d'Identité des Tumeurs® program of the Ligue nationale contre le cancer, characterized reliable biological markers for the identification of patients with Head and Neck Squamous Cell cancer who have a significant risk to develop metastases. Their results are published June 11 in the journal of Clinical Cancer Research.


With more than 600,000 new cases diagnosed worldwide each year, Head and Neck Squamous Cell Carcinoma(HNSCC) represents a major medical problem. It is the fifth most common cancer  in the world and the fourth leading cause of death in men linked to cancer in France. Particularly common in the north-east region of France, this disease affects the epithelium and mucous membranes of the mouth, nose, larynx and pharynx. Excessive consumption of tobacco and alcohol or infection by human papillomavirus are causes of this affection. About 20% of patients will develop metastases in other body regions, a complication that is fatal for most of them, within three years after the detection of cancer. To help physicians tailor therapeutic stratergies, it is crucial to develop tools to detect these particularly high-risk patients.

 

The researchers studied tumours from a hundred HNSCC cancer patients on a genome-wide basis: DNA methylation (methylome), expression of messenger RNA (transcriptome), expression of microRNA (miRNome) and number of DNA copies (genome). The integrated analysis of transcriptome, methylome and miRNome identified a robust subgroup of patients with a particularly high risk to develop metastases among all the patients with HNSCC cancer.

 

The researchers then investigated which biological functions were affected in this subgroup of patients. The researchers found that the affected processes are cell adhesion, programmed cell death, the immune response and the epithelial-mesenchymal transition (in which a cancerous epithelial cell transforms into a mesenchymal cell, free to colonize other body region). This study, first started in 1999, is now part of the program Cartes d'Identité des Tumeurs® funded by the Ligue nationale contre le cancer. This French national project firstly aims to generate a comprehensive database of tumours and secondly provides an integrated statistical analysis whose results are exploited in collaboration with researchers and oncologists.

 

These results provide new evidence for the identification of patients with poor prognosis for HNSCC cancer. Moreover, this fundamental discovery provides significant data to better understand the molecular mechanisms that give tumour cells an advantage to metastasize and to identify tumour biomarkers. It also stresses the importance and value of partnerships between biological, statistical and clinical researchers that can combine their strengths in the fight against cancer.

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