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      Correlation of serum levo-fucose levels as a biomarker with tumor node metastasis staging in oral cancer patients

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          Abstract

          Background:

          oral cancer is a result of disordered cellular behavior initiated by various stimuli which is characterized by the alteration of serum glycoproteins consisting of different monosaccharides. One of these is levo-fucose (L-fucose), a methyl pentose. Elevated levels of protein-bound fucose have been reported in various malignancies.

          Aim:

          The present study attempted to correlate levels of serum L-fucose as a biomarker with the various tumor node metastasis (TNM) stages of oral cancer.

          Methodology:

          The study was carried out on 90 subjects consisting of 30 healthy controls and 60 histopathologically proven oral squamous cell carcinoma (OSCC) cases. The serum fucose level estimation was done based on the method adopted by Winzler. Statistical analysis included independent sample's t-test, one-way ANOVA test, Karl–Pearson correlation test, and Tukey's HSD post hoc test to evaluate the significance and variability of values between groups.

          Results:

          Significant elevation in serum fucose levels was noticed among OSCC patients when compared with the controls and a progressive ascent of L-fucose levels were noted as the stage of severity increased. Serum fucose levels were independent of histopathological grading, age, and sex.

          Conclusion:

          Serum L-fucose levels were increased in OSCC patients, and a positive correlation was observed between serum L-fucose levels and TNM staging of OSCC. Thus, serum L-fucose can be used as an effective diagnostic and prognostic biomarker in OSCC patients.

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          Most cited references19

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          Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy

          Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP)-fucose. GDP-mannose-4,6-dehydratase (GMDS) is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.
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            Cancer biomarkers - current perspectives.

            In the recent years, knowledge about cancer biomarkers has increased tremendously providing great opportunities for improving the management of cancer patients by enhancing the efficiency of detection and efficacy of treatment. Recent technological advancement has enabled the examination of many potential biomarkers and renewed interest in developing new biomarkers. Biomarkers of cancer could include a broad range of biochemical entities, such as nucleic acids, proteins, sugars, lipids, and small metabolites, cytogenetic and cytokinetic parameters as well as whole tumour cells found in the body fluid. A comprehensive understanding of the relevance of each biomarker will be very important not only for diagnosing the disease reliably, but also help in the choice of multiple therapeutic alternatives currently available that is likely to benefit the patients. This review provides a brief account on various biomarkers for diagnosis, prognosis and therapeutic purposes, which include markers already in clinical practice as well as various upcoming biomarkers.
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              Serum fucosylation changes in oral cancer and oral precancerous conditions: alpha-L-fucosidase as a marker.

              The objective of the current study was to investigate the clinical usefulness of serum fucose, fucosylated glycoproteins (fucoproteins), fucosyltransferase (FucT), and alpha-L-fucosidase in oral carcinoma. Blood samples were collected from 130 patients with untreated oral cancer (OC), from 75 patients with oral precancerous conditions (OPC), and from 100 healthy controls. Cancer patients were followed after the initiation of anticancer treatments, and 75 follow-up samples were also collected. Serum levels of fucose and alpha-L-fucosidase were measured spectrophotometrically. Fucoproteins were detected by using lectin-affinity chromatography. FucT activity was analyzed by using radioassay. Serum levels of fucose and fucoprotein were found to be increased significantly in patients with untreated OC compared with controls, patients with OPC, and complete responders (CR) to treatment; whereas the levels were comparable between untreated patients with OC and nonresponders (NR). A similar trend was observed for serum FucT levels, and changes in enzyme activity correlated well with fucose and fucoprotein alterations. The OPC group had significantly increased fucosylation of serum proteins. Furthermore, serum alpha-L-fucosidase activity was markedly higher in patients with untreated OC and in patients with OPC compared with controls. Using receiver operating characteristic curves, a cutoff for alpha-L-fucosidase was determined at >450.6 U/mL, which showed good sensitivity and specificity in OC and OPC compared with controls. The enzyme activity was declined in the CR group but remained higher in the NR group compared with pretreatment levels. Furthermore, various clinicopathologic characteristics were correlated positively with serum fucosylation changes. The findings of the current study suggest that serum fucosylation has clinical usefulness in the detection of early changes and for monitoring treatment response in patients with OC. Among the markers studied, serum alpha-L-fucosidase was identified as a useful marker for close monitoring of patients during post-treatment follow-up.
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                Author and article information

                Journal
                J Pharm Bioallied Sci
                J Pharm Bioallied Sci
                JPBS
                Journal of Pharmacy & Bioallied Sciences
                Medknow Publications & Media Pvt Ltd (India )
                0976-4879
                0975-7406
                October 2016
                : 8
                : Suppl 1
                : S147-S150
                Affiliations
                [1]Department of Oral Medicine and Radiology, Sree Mookambika Institute of Dental Sciences, Kulasekharam, Kanyakumari, Tamil Nadu, India
                Author notes
                Address for correspondence: Dr. P. Redwin Dhas Manchil, E-mail: redwinmanchil@ 123456gmail.com
                Article
                JPBS-8-147
                10.4103/0975-7406.191946
                5074019
                58f51830-c7b7-42c4-8814-de4969612978
                Copyright: © Journal of Pharmacy And Bioallied Sciences

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 06 April 2016
                : 28 April 2016
                : 06 May 2016
                Categories
                Original Research Article

                Pharmacology & Pharmaceutical medicine
                biomarkers,fucose,neoplasms
                Pharmacology & Pharmaceutical medicine
                biomarkers, fucose, neoplasms

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