Skip to main content
Log in

Salivary Glyco-sialylation changes monitors oral carcinogenesis

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AJCC:

American Joint Committee on Cancer

AUC:

Area under curve

CI:

Confidence interval

CR:

Complete responders

ELISA:

Enzyme linked immunosorbent assay

IDV:

Integrated density value

LN:

Lymph node

OPC:

Oral precancerous conditions

MAM:

Maackia amurensis

MU:

Methyl umbelliferone

NR:

Non-responders

PNP:

p-Nitrophenol

PT:

Pretreatment

pTNM:

Pathological tumor node metastasis

RT:

Room temperature

SEM:

Standard error of mean

SNA:

Sambucus nigra agglutinin

ST:

Sialyl transferase

TP:

Total proteins

TSA:

Total sialic acid

References

  1. Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., Forman, D.: Global cancer statistics. CA Cancer J Clin 61, 69–90 (2011)

    Article  PubMed  Google Scholar 

  2. Johnson, N.W., Warnakulasuria, S., Gupta, P.C., Dimba, E., Chindia, M., Otoh, E.C., et al.: Global oral health inequalities in incidence and outcomes for oral cancer: causes and solutions. Adv Dent Res 23, 237–246 (2011)

    Article  CAS  PubMed  Google Scholar 

  3. Madani, H., Dikshit, M., Bhadur, D.: Risk for oral cancer associated to smoking, smokeless and oral dip products. Indian J Public Health 56, 57–60 (2012)

    Article  PubMed  Google Scholar 

  4. Tanaka, T., Ishiqamori, R.: Understanding carcinogenesis for fighting oral cancer. J Oncol 2011, 1–10 (2011)

    Google Scholar 

  5. Neville, B.W., Day, T.A.: Oral cancer and precancerous lesions. CA Cancer J Clin 52, 195–215 (2002)

    Article  PubMed  Google Scholar 

  6. Reis, C.A., Osorio, H., Silva, L., Gomes, C., David, L.: Alterations in glycosylation as biomarkers of cancer detection. J Clin Pathol 63, 322–329 (2010)

    Article  CAS  PubMed  Google Scholar 

  7. Shah, M.H., Telang, S.D., Shah, P.M., Patel, P.S.: Tissue and serum alpha 2–3-and alpha 2–6-linkage specific sialylation changes in oral carcinogenesis. Glycoconj J 25, 279–290 (2008)

    Article  CAS  PubMed  Google Scholar 

  8. Mattox, S., Walrath, K., Ceiler, D., Smith, D.F., Cummings, R.D.: A solid phase assay for the activity of CMP Neu Ac: Galbeta1-4GlcNac-R, alpha2,6-sialyltransferase. Anal Biochem 206, 430–436 (1992)

    Article  CAS  PubMed  Google Scholar 

  9. Harduin-Lepers, A., Vallejo-Ruiz, V., Krzewinski Recchi, M.A., Samyn-Petit, B., Julien, S., Deleannoy, P.: The human sialyl transferase family. Biochemie 83, 727–737 (2001)

    Article  CAS  Google Scholar 

  10. Siddartha, Bhandary, S., Kumari, S., Shetty, R., Babu, S., Shetty, S.: Status of serum sialic acid, antioxidant and lipid peroxidation in head and neck cancer patients. Res J Pharma Biol Chem Sci 2, 1–5 (2011)

    CAS  Google Scholar 

  11. Joshi, M., Patil, R.: Estimation and comparative study of serum total sialic acid levels as tumor markers in oral cancer and precancer. J Cancer Res Ther 6, 263–266 (2010)

    Article  PubMed  Google Scholar 

  12. Sawney, H., Kumar, C.A.: Correlation of serum biomarkers (TSA & LSA) and epithelial dysplasia in early diagnosis of oral precancer and oral cancer. Cancer Biomark 10, 43–49 (2011)

    Google Scholar 

  13. Kadam, C.Y., Katkam, R.V., Suryakar, A.N., Kumbar, K.M., Kadam, D.P.: Biochemical markers in oral cancer. Biomed Res 22, 76–80 (2011)

    CAS  Google Scholar 

  14. Sonmez, H., Suer, S., Gungor, Z., Baloglu, H., Kokoglu, E.: Tissue and serum sialidase levels in breast cancer. Cancer Lett 136, 75–78 (1999)

    Article  CAS  PubMed  Google Scholar 

  15. Reuter, G., Struwe, R., Feige, J., Brede, R., Bumm, P., Schauer, R.: Analysis of carbohydrate composition and sialidase activity in oral secretions of patients with tumors in the upper aerodigestive tract. Eur Arch Otorhinolaryngol 249, 5–11 (1992)

    CAS  PubMed  Google Scholar 

  16. Miyagi, T., Yamaguchi, K.: Mammalian sialidase: physiological and pathological roles in cellular functions. Glycobiol 22, 880–896 (2012)

    Article  CAS  Google Scholar 

  17. Harduin Lepers, A., Krzewinski-Recchi, M.A., Colomb, F., Foulquier, F., Groux-Degrootes, Delannoy, P.: Sialyltransferase functions in cancer. Front. Biosci 4, 499–515 (2012)

    Article  Google Scholar 

  18. Yakob, M., Fuentes, L., Wang, M.B., Abemayor, E., Wong, D.T.W.: Salivary biomarkers for detection of oral squamous cell carcinoma. Current state and recent advances. Curr Oral Health Rep 1, 133–141 (2014)

    Article  PubMed  Google Scholar 

  19. Cheng, Y.S.L., Rees, T., Wright, J.: A review of research on salivary biomarkers for oral cancer detection. Clin Translational Med 3, 1–10 (2014)

    Article  Google Scholar 

  20. Shah, F.D., Begum, R., Vajaria, B.N., Patel, K.R., Patel, J.B., Shukla, S.N., et al.: A review on salivary genomics and proteomics biomarkers in oral cancer. Indian J Clin Biochem 26, 326–334 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Taniguchi, N., Hancock, W., Lubman, D.M., Rudd, P.M.: The second golden age of glycomics: from functional glycomics to clinical applications. J Proteome Res 8, 425–426 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. Drake, P.M., Cho, W., Li, B., Prakobphol, A., Johansen, E., Anderson, N.L., et al.: Sweetening the pot: adding glycosylation to the biomarker discovery equation. Clin Chem 56, 223–236 (2010)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Ghazarian, H., Idoni, B., Oppenheimer, S.B.: A glycobiology review: carbohydrates, lectins and implications in cancer therapeutics. Acta Histochem 113, 236–247 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Vajaria, B.N., Patel, K.R., Begum, R., Shah, F.D., Patel, J.B., Shukla, S.N., et al.: Evaluation of serum and salivary total sialic acid and α-L-fucosidase activity in oral precancerous conditions and oral cancer. Oral Med Oral Pathol Oral Surg 115, 764–71 (2013)

    Article  Google Scholar 

  25. Trivedi, D.J., Trivedi, C.D., Hallikeri, K., Udupa, R.: Salivary sialic acid as marker of oral cancer. Int J Int Sci Inn 1, 48–50 (2012)

    CAS  Google Scholar 

  26. Dhakar, N., Astekar, M., Jain, M., Saawarn, S., Saawarn, N.: Total sialic acid, total protein and total sugar levels in serum and saliva of oral squamous cell carcinoma patients. A case control study. Dent R J 10, 343–347 (2013)

    Google Scholar 

  27. Hemalatha, V.T., Austin, R.D., Manisundar, N., Sarumathi, T., Nisha, V.A.: Evaluation of salivary sialic acid in patients with different clinic-pathological stages of oral leukoplakia and oral squamous cell carcinoma. A cross sectional study. Biosci Biotech Res Asia 10, 419–425 (2013)

    Article  CAS  Google Scholar 

  28. Rasool, M., Ruban Khan, S., Malik, A., Khan, K.M., Zahid, S., Manan, A., Qazi, M.H., et al.: Comparative studies of salivary sialic acid, lipid peroxidation and antioxidant status in oral squamous cell carcinoma (OSCC). Pak J Med Sci 30, 466–471 (2014)

    PubMed Central  PubMed  Google Scholar 

  29. Greene, F.I., Page, D.L., Fleming, I.D.: American joint committee on cancer (AJCC). Head and neck sites. In: Cancer staging manual, 6th edn, pp. 17–87. JB Lippincott, Philadelphia (2002)

    Google Scholar 

  30. Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R., Rubinstein, L., et al.: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92, 205–216 (2000)

    Article  CAS  PubMed  Google Scholar 

  31. Hu, S., Wang, J., Meijer, J., Leong, S., Xie, Y., Yu, T., et al.: Salivary proteomic and genomic biomarkers for primary Sjogren’s syndrome. Arthritis Rheum 56, 588–600 (2007)

    Article  Google Scholar 

  32. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., Randall, R.J.: Protein measurement with the Folin phenol reagent. J Biol Chem 193, 265–275 (1951)

    CAS  PubMed  Google Scholar 

  33. Skoza, L., Mohos, S.: Stable thiobarbituric acid chromophore with dimethyl sulphoxide. Application to sialic acid assay in analytical de-O-acetylation. Biochem J 159, 457–462 (1976)

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Potier, M., Mameli, L., Belisle, L., Dollaire, L., Melancon, S.B.: Fluorometric assay of neuraminidase with a sodium (4-methylumbeliferyl α-D-N-Acetyl neuraminate) substrate. Anal Biochem 94, 287–296 (1979)

    Article  CAS  PubMed  Google Scholar 

  35. Hakomori, S.: Glycosphingolipids in cellular interaction, differentiation and oncogenesis. Annu Rev Biochem 50, 733–764 (1981)

    Article  CAS  PubMed  Google Scholar 

  36. Yeh, J.C., Cummings, R.D.: Absorbance and light based solid phase assays for CMPNeuAc: Galbeta1-4GlcNAc-Ralpha2,3-sialyl transferase. Anal Biochem 236, 126–133 (1996)

    Article  CAS  PubMed  Google Scholar 

  37. Sanjay, P.R., Hallikeri, K., Shivashankara, A.R.: Evaluation of salivary sialic acid and total protein and total sugar in oral cancer: a preliminary report. Ind J Dent Res 19, 288–291 (2008)

    Article  CAS  Google Scholar 

  38. Shubhada, C., Swamy, B.M.: Salivary expression of Sclerotium Rolfsii lectin-binding mucin-type glycoprotein in human oral cancer. J Biosci Tech 3, 455–461 (2012)

    Google Scholar 

  39. Vajaria, B.N., Patel, K.R., Begum, R., Shah, F.D., Patel, J.B., Joshi, G.M., et al.: Significance of glycosyltransferases: ST3GAL1, FUT3, FUT5 and FUT6 transcripts in oral cancer. Glycobiol Insights 4, 7–14 (2014)

    Google Scholar 

  40. Wang, P.H., Li, Y.F., Juang, C.M., Lee, Y.R., Chao, H.T., Ng, H.T., et al.: Expression of sialyl transferase family members in cervix squamous cell carcinoma correlates with lymph node metastasis. Gynecol Oncol 86, 45–52 (2002)

    Article  CAS  PubMed  Google Scholar 

  41. Gessner, P., Riedl, S., Quentmaier, A., Kemmner, W.: Enhanced activity of CMP-neuAc: Galbeta1-4glcNAc:alpha2,6-sialyl transferase in metastasizing human colorectal tumor tissue and serum of tumor patients. Cancer Lett 75, 143–149 (1993)

    Article  CAS  PubMed  Google Scholar 

  42. Dall’Olio, F., Chiricolo, M., D’Errico, A., Gruppioni, E., Altimari, A., Fiorentino, M., et al.: Expression of beta-galactoside alpha2, 6 sialyl transferase and of alpha2, 6-sialylated glycoconjugates in normal human liver, hepatocarcinoma and cirrhosis. Glycobiol 14, 39–49 (2004)

    Article  Google Scholar 

  43. Yamamoto, H., Saito, H., Kaneko, Y., Kersey, D., Yong, V.W., Bremer, E.G., et al.: Alpha2, 3-sialyl transferase mRNA and alpha2, 3-linked glycoprotein sialylation are increased in malignant gliomas. Brain Res 755, 175–179 (1997)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors are thankful to Indian Council of Medical Research (ICMR), New Delhi. The project was partly funded by ICMR Grant No: 5/13/95/2003-NCD-III

Conflict of Interest

None declared.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Prabhudas S. Patel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vajaria, B.N., Patel, K.R., Begum, R. et al. Salivary Glyco-sialylation changes monitors oral carcinogenesis. Glycoconj J 31, 649–659 (2014). https://doi.org/10.1007/s10719-014-9561-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-014-9561-7

Keywords

Navigation