Oral cancer has emerged as an alarming public health problem with increasing incidence and mortality rates all over the world. Therefore, the implementation of newer screening and early detection approaches are of utmost importance which could reduce the morbidity and mortality associated with this disease. Sensitive and specific biomarkers for oral cancer are likely to be most effective for screening, diagnosis, staging and follow-up for this dreaded malignancy. Unlike other deep cancers, oral cancer is located in oral cavity. Hence, the direct contact between saliva and oral cancer lesion makes the measurement of tumor markers in saliva an attractive alternative to serum and tissue testing. The DNA, RNA and protein molecules derived from the living cancer cells can be conveniently obtained from saliva. Thus, salivary biomarkers, a non-invasive alternative to serum and tissue-based biomarkers may be an effective modality for early diagnosis, prognostication and monitoring post therapy status. In the current post-genomic era, various technologies provide opportunities for high-throughput approaches to genomics and proteomics; which have been used to evaluate altered expressions of gene and protein targets in saliva of oral cancer patients. The emerging field of salivary biomarkers has great potentials to prove its clinical significance to combat oral cancer. Hence, we have reviewed importance of several salivary genomics and proteomics biomarkers for oral cancer.
Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration.
The results suggested that HPV 16 and 18 do not play an important role in oral carcinogenesis in the population from Gujarat, West India. However, HPV 16 is highly prevalent in the cervical cancer patients, which may be considered for planning of prevention programs such as screening and vaccination in women from this region.
Alterations in cell membrane glycosylation play important role in oral carcinogenesis. The present study evaluated salivary sialylation changes i.e. total sialic acid (TSA), sialidase activity, linkage specific (α2-3 and α2-6) sialoproteins and sialyl transferase (ST) activity in controls, patients with oral precancerous conditions (OPC) and oral cancer. Subjects enrolled included 100 controls, 50 patients with OPC, 100 oral cancer patients, and 30 post treatment follow-ups. TSA was estimated by spectrophotometric method, sialidase activity by spectrofluorometric assay and linkage specific biotinylated lectins (α2-3: sambucus nigra agglutinin and α2-6: maackia amurensis agglutinin) were used to detect α-2,3 and α-2,6 STs and sialoproteins by ELISA and dot blot respectively. An increasing trend of salivary TSA/TP ratio, sialidase activity, α2-3 sialoproteins, α-2,3 and α-2,6 ST activities was observed from controls to patients with OPC to oral cancer patients and levels were significantly elevated in oral cancer patients as compared to the controls. Sialidase activity exhibited significant association with metastasis and infiltration. Sialidase activity, TSA/TP ratio, α-2,3 and α-2,6 ST activities were found to be higher in patients with metastasis as compared to patients without metastasis. A progressive increase in TSA/TP ratio, sialidase activity, α2-3 and α2-6 sialoproteins was observed from controls to early to advanced stage of the disease. Sialidase activity, α2-3 and α2-6 sialoproteins and ST activities were found to be decreased in complete responders; while levels were elevated in non-responders. The results documented utility of salivary sialylation endpoints, a non invasive tool in monitoring of oral carcinogenesis.
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