Isolation, Quantification and Kinetics of Salivary Ap4A, SCCA and TROP2 in Patients With Oral Cancer and Potentially Malignant Oral Disorders

In the last few years, treatment of oral cancer (OC) showed improvement due to the combined efforts of surgery, radiotherapy and chemotherapy. Nevertheless the long-term survival rate, only marginally improved with a five year survival rate of 50%.

OC is preceded by a preinvasive stage, which may last for many years. Tumor progression in epithelia has been classified as normal, hyperplastic (non-dysplastic), dysplastic carcinoma in situ and invasive carcinoma. The majority of the initial alterations of precancerous and cancerous oral lesions are often non recognizable, even by histopathological examination. The basic biology of initiation and progression of these tumors is still obscure. Carcinogenesis is a process which includes initiation, promotion and progression, driven by accumulation of specific altered genes. Tumor cells produce biochemical substances called tumor markers. Some of these substances found in healthy individuals, but with altered quantitative ratio. Besides the salivary DNA and RNA, other markers are detectable in saliva, such as cell cycle markers (p53, p16 etc.), growth factors (EGF, TGF, etc.), cell surface markers, oxidants and antioxidants and other. Because of its accessibility, non-invasive approach and location proximity, saliva presents an ideal tool for the research of OC tumor markers.

This study will analyze the role of Diadenosine tetraphosphate (Ap4A), Squamous Cell Carcinoma associated Antigen 1 and 2 (SCCA1 and 2) and Trophoblast Cell Surface Antigen (TROP2) in the development of OC.

Ap4A is the only diadenosine polyphosphate that can induce a considerable increase in [Ca2+] in endothelial cells, indicating that its vasoactive effects are comparable to the known effects of arginine vasopressin, angiotensin II and adenosine triphosphate (ATP). Ap4A is a ubiquitous diadenosine polyphosphate signal molecule for DNA replication in mammalian cell.

Level of Ap4A was found to be directly related to the proliferative activity of the cells. It is considered that the Ap4A has an important role in the regulation of cellular growth and division. In the absence of the tumor suppressor gene FHIT (Fragile Histidine Triad), located on the chromosome 3p, Ap4a accumulates and leads to DNA synthesis and multiplication of cells. Loss of heterozygosity of the chromosome 3p is believed to be a common event in the early phase of carcinogenesis.