Abstract 24P
Background
Nasopharyngeal carcinoma (NPC) has excellent local control in the IMRT era. Nevertheless, distant metastases are the leading cause of death and challenge the scientific community. We report our results of mass-spectrometry based research for biomarkers to predict metastasis.
Methods
We retrieved clinical image and outcomes of biopsy-proven untreated NPC patients between 2009 and 2013 treated with IMRT with or without concurrent chemotherapy. One slice of 10um of formalin-fixed paraffin-embedded sample from each patient was submitted to label-free quantitative proteomics analysis. Label-free quantification was carried out using MaxQuant software V1.6.0.16. Database searches were performed using the Andromeda search engine with the UniProt-SwissProt Human Uniprot Proteome database as a reference and a contaminants database of common contaminants. Clinical results of distant metastasis outcomes were compared to proteomic analysis.
Results
We retrieved 82 patients, from which 18 developed distant metastases (M1). A pool of 25 proteins significantly up-regulated and 303 proteins down-regulated in M1 patients. Among differentially expressed proteins, tumor protein D54 (TPD54) had the highest difference in M1 patients (-Log(P-value) = 6,223915243; Difference = -0,466002574; Gene TPD52L2; p<0.01). Other proteins are CALM-1, SGT1, immunoglobulin, and ribosomal proteins (p<0.01). Among signalling pathways found, Ras-related protein Rab-33A (gene RAB33A) was significantly up-regulated in M1 patients (p<0.01).
Conclusions
We report a tumour profiling of 25 proteins up-regulated in metastatic NPC from a European cohort. TPD54 was identified as a potential biomarker candidate for metastasis prediction, and Ras GTPase signaling pathway was also up-regulated in metastatic patients.
Clinical trial identification
Editorial acknowledgement
Prof. J.L. Capelo-Martínez for his assistance in this study.
Legal entity responsible for the study
The authors.
Funding
IPOLFG Research Fund [grant 2015/UIC901].
Disclosure
All authors have declared no conflicts of interest.