Characterization of laryngeal squamous cell carcinoma: molecular profiling of p75 neurotrophic receptor in cancer stem cells and circulating tumour cells to predict tumour aggressiveness and treatment response.
This project will investigate the oncogenic and metastatic potential of Laryngeal Squamous Cell Carcinoma (LSCC) through the analysis of p75 Neurotrophin Receptor (p75NTR) expression in Cancer Stem Cells (CSCs) and Circulating Tumour Cells (CTCs). Preliminary evidence of CSCs in LSCC has been demonstrated, while the presence and significance of CTCs in this type of cancer is still uncertain. We have recently isolated CTCs from blood of LSCC patients, and shown that they correlate well with patient post-operative outcome and disease-free survival. However, given CTCs heterogeneity in surface adhesion molecules expression, the standard CTCs isolation suffers from false negatives, with serious limitations to their study in LSCC. The p75NTR is expressed in mitotically quiescent CSCs population of the laryngeal epithelia, and also in CTCs in other cancers, thus we hypothesise that p75NTR might represent a further and efficient marker for CSCs/CTCs in LSCC. More, since p75NTR is a reliable index of tumorigenicity, invasiveness and chemotherapy resistance, it is likely that p75NTR expression correlates with the acquisition and maintenance of CSCs properties in LSCC. To test this hypothesis, the expression of full length and cleaved forms of p75NTR associated with stemness, survival, cell migration, and chemoresistance markers will be analysed in laryngeal primary tumour and locoregional lymph nodes, and in preoperative and post-operative blood-derived CTCs from LSCC patients. The molecular data will be correlated with clinico-pathological parameters, such as tumour aggressiveness and disease-free survival. This experimental approach is believed to make a better pre-operative patient stratification through prediction of tumour aggressiveness, achieve a timely diagnosis prior to metastasis through liquid biopsy, and improve post-treatment surveillance. The data obtained might also help to identify and target the p75 pathway as a promising novel approach in LSCC therapy.