Proteomics analysis of the invasive front and lymph node in head and neck squamous cell carcinomas using MALDI-imaging mass spectrometry

Abstract

Lymph node metastasis is the main prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC), and can decrease the 5-year survival rates to lower than 50%. The molecular signals involved in this complex process are poorly characterized for HNSCC, and no molecular markers are currently used in clinical practice. In this context, our FAPESP post-doctorate fellowship project (Process 2015/19191-6) was designed to determine the proteomic profile of the primary tumor invasive front and lymph node metastasis sites of HNSCC using LC-MS/MS, and verify the association with local metastasis. As a complement for this main project, we propose a BEPE project to determine the proteomic profile of the same sites using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). MALDI-IMS methodology allows mass spectrometric analyses in intact tissue sections and has several advantages over conventional methodologies, including spatial information of the proteins within tissues. The proteomic profile will be determined for selected cell populations in the invasive front (tumor and stroma cells) and lymph nodes (metastasis and microenvironment cells), and compared between two groups of HNSCC patients classified according to the presence of local metastasis. The results obtained by MALDI-IMS will complement the proteins identified by LC-MS/MS in the FAPESP post-doctorate fellowship. By this approach, we will describe potential markers associated with the prognosis of patients with HNSCC, and reveal molecular mechanisms involved in the development and progression of this neoplasm.