A primary tumor gene expression signature identifies a crucial role played by tumor stroma myofibroblasts in lymph node involvement in oral squamous cell carcinoma
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Gianluigi Mazzoccoli1, Stefano Castellana2, Massimo Carella3, Orazio Palumbo3, Cristiana Tiberio1, Caterina Fusilli2, Daniele Capocefalo2, Tommaso Biagini2, Tommaso Mazza2,* and Lorenzo Lo Muzio4,*
1Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo (FG), Italy
2Bioinformatics Unit, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo (FG), Italy
3Medical Genetics, IRCCS Scientific Institute and Regional General Hospital “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo (FG), Italy
4Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
*These authors have contributed equally to this work
Gianluigi Mazzoccoli, email: [email protected]
Keywords: OSCC; gene signature; metastasis; transcriptome; myofibroblast
Received: March 07, 2017 Accepted: August 07, 2017 Published: September 05, 2017
Oral squamous cell carcinoma (OSCC) is the most common oral and pharyngeal cancer, and is responsible of approximately 3% of cancers in men and 2% in women in the Western World, with increasing incidence rates in developing countries. Early detection by screening is necessary to prevent fatal disease because early, curable lesions are rarely symptomatic. The overall 5-yr survival rate is approximately 50% when surgery, radiation, or both are employed as treatment options, but lymph node involvement greatly influences this estimate, by decreasing the survival rate by about 50%. Here, we aimed at finding genetic signatures associated with lymph node metastasis in OSCC patients. We addressed this issue by whole transcriptome analysis through microarray expression profiling of a set of OSSC specimens of patients without lymph node involvement (10 patients, mean age ± SD 61.2±13.8, male 7, female 3) and with lymph node involvement (11 patients, mean age ± SD 62.1±15.1, male 8, female 3). We evidenced a gene expression signature associated to muscle contraction-related genes in specimens obtained from OSCC patients with lymph node involvement. This gene signature suggests the presence of myofibroblasts in tumor stoma of patients with lymph node involvement and emphasizes the decisive role played by myofibroblasts probably through their secretome in determining OSCC invasiveness.
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