Increased nicotinamide phosphoribosyltransferase and cystathionine-beta-synthase in oral cavity squamous cell carcinomas

Background: Oral squamous cell carcinoma is a major cause of cancer-related deaths world-wide. Histologically it arises from the benign squamous epithelium lining the oral cavity and is conventionally divided into well, moderate, and poorly differentiated subtypes. Nicotinamide phosphoribosyltransferase catalyses the rate-limiting step of nicotinamide adenine dinucleotide synthesis and is highly expressed in many malignancies. Cystathionine-beta-synthase synthesizes hydrogen sulfide and shows increased expression in several malignancies. The expression of both enzymes and cellular hydrogen sulfide levels are known to cooperate to increase tumor survival and promote tumor dedifferentiation. Methods: We employed tissue microarray studies to analyze nicotinamide phosphoribosyltransferase and cystathionine-beta-synthase protein levels in oral squamous cell carcinoma. One-hundred and fifty-one different oral squamous cell carcinomas were analyzed for nicotinamide phosphoribosyltransferase protein levels and 233 oral squamous cell carcinomas were analyzed for cystathionine-beta-synthase protein levels. Results: The expression of both proteins is increased in oral squamous cell carcinoma and is also increased with increasing squamous cell carcinoma grade. Conclusions: Nicotinamide phosphoribosyltransferase and cystathionine-beta-synthase are both increased in oral squamous cell carcinoma and likely cooperate to promote oral squamous cell carcinoma growth and cancer progression. Additionally as both enzymes, particularly cystathionine-beta-synthase, increase with increasing squamous cell carcinoma grade, our data further suggests that higher expression of both enzymes promote tumor dedifferentiation.