Uroporphyrinogen decarboxylase gene expression in oral squamous cell carcinomas.

Abstract

e17002 Background: Oral cancer is one of the most common cancers in India. Uroporphyrinogen decarboxylase (UROD), a key regulator of heme biosynthesis, has recently been suggested as a novel tumor-selective radiosensitizing target against head and neck cancers. Further, a recent study has suggested that tumors with UROD expression may have poorer outcomes and higher rates of recurrence. We tested the expression of UROD splice variants in oral cancer patients who were treated in our hospital to study its expression and impact on the patients. Methods: The expression of both coding and noncoding splice variants of UROD gene was tested in 42 patients (31 male, 11 female) with oral cavity squamous cell carcinomas treated in 2011-12. Pretreatment tumor biopsies were collected and mRNA was extracted using Quiagen RNeasy kit method. cDNA was synthesized using Superscript III and subjected for UROD expression using specific primers. UROD expression and clinical data of patients were analyzed using IBM SPSS 20 Software. Results: The mean age of the patients was 52 years (range 32-70). Buccal mucosa (n=17) and tongue (n=13) were the most common subsites. Seventy six percent had locally advanced disease (T3/T4 and node-positive) and high-grade (70%) cancers. Chemoradiotherapy (CRT) (n =25) and chemotherapy (CT) (n = 10) was given in 35 patients of which 5 had progressive disease. The mean follow up was 11 months. Thirty seven patients were operated, 5 developed locoregional recurrence and 2 developed spine metastases and died during follow-up. UROD was expressed in 23 (54.8%) patients (coding variant = 52.8%, noncoding = 26%). There was no correlation between UROD expression and age, sex, subsite, stage, grade or node positivity. Patients with UROD expression had a slightly poorer response to CRT/CT (30.4% vs 24.1%; p =NS). Similarly, though they had a slightly higher incidence of recurrence, the difference was not significant. Both patients with spinal recurrence had UROD expression. Conclusions: UROD is highly expressed in oral cancer patients in India. Its proposed radiosensitizing and prognostic role in treatment and outcomes though promising needs further evaluation in a larger number of patients.