Skip to main content
PMC home page
Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2004 Jul;19(2):60–71. doi: 10.1007/BF02894259

Clinical usefulness of alterations in sialic acid, sialyl transferase and sialoproteins in breast cancer

G N Raval 1,✉, L J Parekh 2, D D Patel 1, F P Jha 1, R N Sainger 1, P S Patel 1,✉
PMCID: PMC3454218  PMID: 23105458

Abstract

Sialic acid, the end moieties of the carbohydrate chains are biologically important and essential for functions of glycoconjugates and are reported to be altered in cancer patients. Two hundred and twenty five breast cancer (BC) patients, 100 patients with benign breast disease (BBD) and 100 healthy females (controls) were enrolled for the study. Eight hundred and twenty four follow-up samples of 225 breast carcinoma patients were also evaluated. The association of sialic acid forms, sialyltransferase and α-2–6 sialoproteins levels with presence and extent as well as prognosis of breast carcinoma was studied. Serum sialic acid forms and sialyltransferase revealed significantly elevated levels among untreated breast cancer patients as compared to the controls, patients with BBD as well as cancer patients in remission. Non-responders showed comparable levels of the markers with those found in breast cancer patients at the time of diagnosis. Higher levels of sialic acid forms at diagnosis were associated with poor prognosis. A positive correlation between serum levels of different forms of sialic acids and extent of malignant disease was observed. The changes in serum proteins with terminal α-2–6 sialic acid correlated well with alterations in the levels of sialic acid forms and sialyltransferase. Malignant tissues showed elevated levels of sialic acid and sialyltransferase as compared to surrounding normal tissues.

The results suggested potential utility of these markers in evaluation of clinical outcome.

Key Words: Breast Cancer, Glycoproteins, Sialic acid, Sialyltransferase, Tumours

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

References

  • 1.Hakomori S. Aberrant glycosylation in tumour and tumour-associated carbohydrate antigens. Adv. Cancer Res. 1989;52:257–331. doi: 10.1016/s0065-230x(08)60215-8. [DOI] [PubMed] [Google Scholar]
  • 2.Passaniti A., Hart G.W. Cell surface sialylation and tumour cell metastatic potential of B16 melanoma variants correlates with their relative number of specific penultimate with oligosscharide structure. J. Boil. Chem. 1988;263:7591–7603. [PubMed] [Google Scholar]
  • 3.Yogeeswaran G. Metastatic potential is positively correlated with cell surface sialylation of cultured murine cell lines. Science. 1981;212:1514–1516. doi: 10.1126/science.7233237. [DOI] [PubMed] [Google Scholar]
  • 4.Singhal A., Hakomori S. Molecular changes in carbohydrate antigens associated with cancer. Bioassays. 1990;12:223–230. doi: 10.1002/bies.950120506. [DOI] [PubMed] [Google Scholar]
  • 5.Rademacher T.W., Parekh R.B., Dwek R.A. Glycobiology. Annu. Rev. Biol. Chem. 1988;57:785–838. doi: 10.1146/annurev.bi.57.070188.004033. [DOI] [PubMed] [Google Scholar]
  • 6.Feijoo C., Paez-de-la, Cadena M., Rodriguezberrocat F.J. Sialic acid level in serum and tissue from colorectal cancer patients. Cancer Lett. 1997;112:155–160. doi: 10.1016/S0304-3835(96)04564-8. [DOI] [PubMed] [Google Scholar]
  • 7.Paszkowaska A., Berbec H., Semczuk A., Cybulski M. Sialic acid concentration in serum and tissue of endometrial cancer patients. Eur. J. Obstet. Gynecol. Reprod. Biol. 1998;76:211–215. doi: 10.1016/S0301-2115(97)00176-0. [DOI] [PubMed] [Google Scholar]
  • 8.Dall'olio F., Trere D. Expression of alpha 2,6 sialylated sugar chain in normal and neoplastic colon tissues. Detection by digoxigenin conjugated sambucus nigra aglutinin. Eur. Jr. Histochem. 1993;37:257–265. [PubMed] [Google Scholar]
  • 9.Marth E., Flaschka G., Stiegler S., Mose J. Sialic acid as a marker for differentiation between benign and malignant intracranial tumours. Clinica. Chimica. Acta. 1988;176:251–258. doi: 10.1016/0009-8981(88)90184-2. [DOI] [PubMed] [Google Scholar]
  • 10.Kelm S., Schauer R. Sialic acid in molecular and cellular interaction. Int. rev. cytol. 1997;175:137–240. doi: 10.1016/S0074-7696(08)62127-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Gatchev O., Rastam L., Lindberg G., Gullberg B., Eklund G.A., Tornberg S. Tumours of the central nervous system and serum sialic acid concentration in men and women. Br. J. Cancer. 1993;68:425–427. doi: 10.1038/bjc.1993.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Schauer R., Corfield A.P. Occurance of sialic acids-chemistry, metabolism and function. In: Schauer R., editor. Cell biology monographs. New York: Springer Verlag; 1982. pp. 5–50. [Google Scholar]
  • 13.Vierbuchen M.J., Fruectnicht W., Brackrock S., Kranse K.T., Zienkiewicz T.J. Quantitative lectin histochemical and immunochemical studies on the occurance of alpha 2, 6-linked sialic acid residues in colorectal carcinomas. Relation to clinicopathological features. Cancer. 1995;76:727–735. doi: 10.1002/1097-0142(19950901)76:5<727::AID-CNCR2820760504>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  • 14.Holmes E., Osterander G., Hakomori S. Biosynthesis of the sialyl-LeX determinant carried out by type-2 chain glycosphingolipids (IV 3 NeuAcIII3 FucnLc4, Vi3NeuAcV3FucnLc6 and Vi3 NeuAcIII3 V3 Fuc2 nLc6) in human lung carcinoma cell lines. J. Biol. Chem. 1986;261:3737–3743. [PubMed] [Google Scholar]
  • 15.UICC TNM classification of malignant tumours. (1980) UICCTechnical Report series. Seller A.H. (ed). 1st edition, 7.
  • 16.Miller A.B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–214. doi: 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  • 17.Skoza L., Mohos S. Stable thiobarbituric acid chromophore with dimethyl sulfoxide. Application to sialic acid assay in analytical De-O-acetylation. Biochem. J. 1976;159:457–462. doi: 10.1042/bj1590457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Warren L., Buck C.A., Tuszynski G.P. Glycopeptide changes and malignant transformetios: A possible role for carbohydrate in malignant behaviour. Biochim. Biophys. Acta. 1978;516:97–127. doi: 10.1016/0304-419x(78)90005-7. [DOI] [PubMed] [Google Scholar]
  • 19.Winzler R.J. Methods of biochemical analysis. New York: Intersciences Publishers; 1955. Determination of serum glycoproteins; pp. 279–311. [DOI] [PubMed] [Google Scholar]
  • 20.Kessel D., Allen J. Elevated plasma sialytransferase in the cancer patients. Cancer Res. 1975;35:670–672. [PubMed] [Google Scholar]
  • 21.Thompson S., Turner G.A. Elevated levels of abnormally fucosylated heptoglobins in cancer sera. Br. J. Cancer. 1987;56:605–610. doi: 10.1038/bjc.1987.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Noursis M.J. SPSS for windows. SPSS Advanced stastic release 7.5. Chicago: SPSS Inc; 1996. [Google Scholar]
  • 23.Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 1958;34:457–481. doi: 10.2307/2281868. [DOI] [Google Scholar]
  • 24.Cox A.R. Regression analysis model and life table. J. Stat. Soc. (Br.) 1972;34:187–198. [Google Scholar]
  • 25.Patel P.S., Baxi B.R., Adhvaryu S.G., Balar D.B. Evaluation of serum sialic acid, heat stable alkaline phosphatase and fucose as markers of breast carcinoma. Anticance. Res. 1990;10:1071–1074. [PubMed] [Google Scholar]
  • 26.Patel P.S., Raval G.N., Rawal R.M., Patel G.H., Balar D.B., Shah P.M., Patel D.D. Comparision between serum levels of carcinoembryonic antigen, sialic acid and phosphohexose isomerase in lung cancer. Neoplasma. 1995;42:53–56. [PubMed] [Google Scholar]
  • 27.Raval G.N., Parekh L.J., Patel M.M., Patel P.S., Rawal R.M., Balar D.B., Patel D.D. Role of sialic acid and alkaline DNase in breast cancer. The Int. Jr. Biol. Markers. 1997;12:61–67. doi: 10.1177/172460089701200204. [DOI] [PubMed] [Google Scholar]
  • 28.Kobata A., Takasaki S. Structural characterization of oligo-saccharides from glycoproteins. In: Fukuda M., Kobata A., editors. Glycobiology: A practical approach. New York: Oxford University Press; 1993. pp. 165–85. [Google Scholar]
  • 29.Varki A. Biological roles of oligosaccharides: All of the theories are correct. Glycobiology. 1993;3:97–130. doi: 10.1093/glycob/3.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Baxi B.R., Patel P.S., Adhvaryu S.G., Dayal P.K. Usefulness of serum glycoconjugates in precancerous and cancerous disease of the oral cavity. Cancer. 1991;67:135–140. doi: 10.1002/1097-0142(19910101)67:1<135::AID-CNCR2820670124>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  • 31.Sashikantha M.C., Rao B.B. Study of serum fucose and serum sialic acid levels in oral squmous cell carcinoma. Ind. J. Dent. Res. 1994;5:119–124. [PubMed] [Google Scholar]
  • 32.Gosh M., Nayak B.R. Serum sialic acid, fucose, sialic acid/fucose ratio as tumour marker in oral cancer. Annals of Densitry. 1991;50:33–35. [PubMed] [Google Scholar]
  • 33.Ogoshi K., Miyaji M., Nakamura K., Kondoh Y., Makuuchi H., Tajima T. Immuntherapy and combined assay of serum level of CEA and acute phase reactants. Cancer Immunol. Immunotherapy. 1997;46:14–20. doi: 10.1007/s002620050454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Fernandez-Rodriguez J., Paez-de-la-cadena M., Martinez-zorzano V.S. Fucose level in serum and in tumor of colorectal adenocarcinoma patients. Cancer Lett. 1997;121:147–53. doi: 10.1016/S0304-3835(97)00343-1. [DOI] [PubMed] [Google Scholar]
  • 35.Patel P.S., Raval G.N., Patel M.M., Balar D.B., Patel D.D. Electrophoretic pattern of serum glycoproteins on polyacrylamide disc gel in patients with breast cancer. Anticancer Res. 1996;16:2089–2094. [PubMed] [Google Scholar]
  • 36.Alhadeff J.A. Malignant cell glycoproteins and glycolipids. CRC Crit. Rev. in Oncol. Hematol. 1989;9:37–107. doi: 10.1016/S1040-8428(89)80014-9. [DOI] [PubMed] [Google Scholar]
  • 37.Feizi T, Childs R.A. Carbohydrates as antigenic determinants of glycoproteins. Biochem. J. 1987;245:1–11. doi: 10.1042/bj2450001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Miles D.W., Happerfield L.C., Smith P., Gillibrand R., Bobrow L.G., Gregory W.M., Rubens R.D. Expression of sialyl Tn predicts the effect of adjuvant chemotherapy in node positive breast cancer. Br. J. Cancer. 1994;70:1272–1275. doi: 10.1038/bjc.1994.486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Muryama T., Zuber C., Seelentag W.K., Li W.P., Kemmner W., Heiz P.U., Roth J.L. Colon carcinoma glycoprotein carrying alpha 2,6-linked sialic acid reactive with sambucus nigra agglutinin are not constitutively expressed in normal human colon mucosa and are distinct from sialyl Tn antigen. Int. J. Cancer. 1997;70:575–581. doi: 10.1002/(SICI)1097-0215(19970304)70:5<575::AID-IJC14>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  • 40.Gessner P., Riedl S., Quentmaier A., Kemmno W. Enhanced activity of CMP-NeuAc: Gal beta 1-4GlcNAc:alpha 2–6 Sialyltransferase in metastasizing tumour tissue and serum of tumour patients. Cancer Lett. 1993;75:143–149. doi: 10.1016/0304-3835(93)90056-F. [DOI] [PubMed] [Google Scholar]
  • 41.Shimada I., Shoji M., Futu-suya R., Katoh T., Kominato Y., Sakamoto T., Fujikura T. Elevation of ratio of urinary N-acetyl Neuraminlactose to free sialic acids in some advanced cancer patients. J. Gastroentrol. 1995;75:143–149. doi: 10.1007/BF01211370. [DOI] [PubMed] [Google Scholar]
  • 42.Lileng R., Tved K., Nesland J.M., Reed W., Erikstein B.K., Funderud S. CDW75 antigen expression in breast cancer. Pathol. Res. Pract. 1993;189:394–398. doi: 10.1016/S0344-0338(11)80325-0. [DOI] [PubMed] [Google Scholar]
  • 43.Yamamoto H., Kaneko Y., Vandermulan D., Kersey D., Mkrdichian E., Leestma J., Moskal J.R. The expression of CMP-NeUAc: Gal beta 1,4 Glc Nac, alpha 2,6 sialyltransferase (E.C 2.4.99.1) the glycoprotein bearing alpha 2,6-linked sialic acids in human brain tumours. Glycoconjugate J. 1995;12:848–856. doi: 10.1007/BF00731247. [DOI] [PubMed] [Google Scholar]
  • 44.Dao T.L., Ip C., Patel J. Serum sialyltransferase and 5′nucleotidase as reliable biomarkers in women with breast cancer. J. Natl. Cancer. Invst. 1980;65:529–534. [PubMed] [Google Scholar]
  • 45.Nakata B., Chung K.H., Maguruma K., Yamashita Y., Inoue T., Matsuoka T., Onoda N., Kato Y., Sakurai M., Sowa M. Changes in tumor marker levels as a predictor of chemotherapeutic effect in patients with gastric carcinoma. Cancer. 1998;83:19–24. doi: 10.1002/(SICI)1097-0142(19980701)83:1<19::AID-CNCR3>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  • 46.Suer S., Sonmez H., Karaaslan I., Baloglu H., Kokoglu E. Tissue sialic acid and fibronectin levels in human prostatic cancer. Cancer Lett. 1996;99:135–137. doi: 10.1016/0304-3835(95)04084-6. [DOI] [PubMed] [Google Scholar]
  • 47.Wang J.W., Ambros R.A., Weber P.B., Rosano T.G. Fucosyl transferase and α-L fucosidase and fucose level in normal and malignant endometrial tissue. Cancer Res. 1995;55:3654–3658. [PubMed] [Google Scholar]
  • 48.Akamatsu S., Yazawa S., Tachikawa T., Furuta T., Okaichi Y., Nakamura T., Asao T., Nagamachi Y. Alpha 2–3 sialyltransferase associated with the synthesis of CA19-9 in colorectal tumours. Cancer. 1996;77:1694–1700. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1694::AID-CNCR41>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Clinical Biochemistry are provided here courtesy of Springer

RESOURCES