Analysis Of The Extracellular Vesicles Content Present In The Plasma Of Patients With Head And Neck Squamous Cell Carcinoma For Identification Of Molecular Markers For Treatment Response

Previous data showed that induction chemotherapy (IC) with cisplatin and paclitaxel followed by chemoradiotherapy (CRT) based on cisplatin is safe, well tolerated and improves overall survival for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) (stage III -IV). However, approximately 30% of these patients have incomplete response to IC and CRT and there is no clinical marker able to segregate these patients from those that respond to the treatment. The recent discovery of extracellular vesicles (EVs) in different body fluids carrying proteins and nucleic acids may indicate an alternative route for new specific markers present in the plasma of patients with HNSCC. In this study, Cholera toxin B chain (CTB) and Annexin V (AV) which respectively binds GM1 ganglioside and phosphatidylserine, were used to isolate EVs from plasma of HNSCC patients that respond and not respond to IC and CRT. The proteins in the vesicles were identified using antibody array through a pool of 6 responders’ patients (R) in comparison to 6 patients with incomplete response (IR). A total of 327 proteins were identified into CTB-EVs, from which 54 and 20 proteins were exclusive to R and IR patients, respectively. Beside this, 271 proteins were identified into AV-EVs, from which 20 proteins were present in R patients and other 20 proteins were present only in IR ones. A preliminary analysis of this data revealed that HNSCC resistant patients have elevated levels of TGFβ3 in CTB-EVs while patients with incomplete response have elevated levels of HSP90AB1 in AV-EVs. This study demonstrated the successful use of CTB and AV to isolate circulating plasma EVs for biomarker discovery in HNSCC and represents a novel technology that can be applied to segregate patients that may respond or not to IC or CRT. Citation Format: Dorival Mendes Rodrigues-Junior, Soon Sim Tan, Sai Kiang Lim, N Gopalakrishna Iyer, Andre Luiz Vettore. Analysis of the extracellular vesicles content present in the plasma of patients with head and neck squamous cell carcinoma for identification of molecular markers for treatment response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3150.