PADI4 expression in baseline circulating tumour cells acts as a prognostic biomarker in oral squamous cell carcinoma

Abstract

Oral Squamous Cell Carcinoma (OSCC), one of the most prevalent cancers in developing countries. It is associated with poor prognosis due to relapse in a significant number of patients. Circulating tumour cells (CTCs) are precursors for metastasis and thought to be key players in early relapse in various cancers including OSCC. Though CTC enumeration has been associated with disease outcome, in-depth molecular analysis of CTCs remained minimal as the techniques for CTC isolation and analysis are challenging. While exploring gene expression in CTCs, we performed whole transcriptome analysis of paired primary tumour and CTCs isolated from Oral Squamous Cell Carcinoma (OSCC) patients. Various genes were found to be differentially expressed in CTCs. We found PADI4 gene was significantly upregulated in CTCs. PADI4 gene encodes for an enzyme that converts arginine to citrulline.

PADI4 expression in primary tumours was previously observed to be associated with metastasis. Here, we are reporting PADI4 expression for the first time in CTCs and its association with relapse. Interestingly in our data, PADI4 expression was more seen in CTCs with EMT (epithelial to mesenchymal transition)-phenotype than with CTCs only epithelial-phenotype. In conclusion, this is the first study presenting the potential prognostic utility of PADI4 expression in CTCs isolated from OSCC patients.