Document Type : Review Article(s)


1 Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

2 Department of Food and Drug Deputy, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Biochemistry, Payame Noor University, Tehran, Iran

4 Non-communicable Diseases Institute, Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran

5 Imam Khomeini Educational Hospital, Mazandaran University of Medical Sciences, Sari, Iran



Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide and is a leading cause of cancer-related mortality. Since many colon cancers present no significant clinical symptoms, identifying new biomarkers or a set of biological indicators significant for clinical trials is crucial for the early detection of CRC. This advancement also aids in establishing new objectives for interventional therapeutic strategies against the disease. Currently, research is exploring various proteins, glycoproteins, and cellular and humoral substances involved in cellular homeostasis mechanisms as potential cancer markers. This review examines the potential utility of fucosylation and sialylation processes, as well as sex hormones, as biomarkers in the diagnosis and prognosis of CRC. A comprehensive search was conducted in PUBMED, MEDLINE, and Google Scholar, supplemented by a manual search of relevant journals. The keywords were L-fucose, sialic acid, fucosyltransferase-4, galectin-3, and steroid hormones in CRCs.


Durdi Qujeq (Google Scholar)

Roya Abbasi Natajomrani (Google Scholar)


Main Subjects

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.98579.1910

  1. Zhao JY, Que WQ, Tang J, Li JM, Su XQ, Guo YJ. Colorectal cancer survivors' experiences of return-to-work: A meta-synthesis of qualitative studies. Eur J Oncol Nurs. 2023;63:102284. doi: 10.1016/j.ejon.2023.102284.
  2. López-Cortés R, Muinelo-Romay L, Fernández-Briera A, Gil-Martín E. Inhibition of α(1,6)fucosyltransferase: effects on cell proliferation, migration, and adhesion in an syngeneic colorectal cancer model. Int J Mol Sci. 2022;23(15):8463. doi: 10.3390/ijms23158463.
  3. Lv C, Luo K, Liu S. Fucosyltransferase 4 predicts patient outcome in rectal cancer through an immune microenvironment-mediated multi-mechanism. J Oncol. 2022;2022:4637570. doi: 10.1155/2022/4637570.
  4. Janbabaei G, Hedayatizadeh-Omran A, Alizadeh-Navaei R, Moradi S, Ahmadi A, Alashti MR, et al. An epidemiological study on patients with colorectal cancer admitted to one referral center in north of Iran from 2006 to 2015. WCRJ. 2017;4(1): e841. doi: 10.32113/wcrj_20173_841.
  5. Klimeck L, Heisser T, Hoffmeister M, Brenner H. Colorectal cancer: A health and economic problem. Best Pract Res Clin Gastroenterol. 2023;66:101839. doi: 10.1016/j.bpg.2023.101839.
  6. Armitage EG, Barbas C. Metabolomics in cancer biomarker discovery: current trends and future perspectives. J Pharm Biomed Anal. 2014;87:1-11. doi: 10.1016/j.jpba.2013.08.041.
  7. Das V, Kalita J, Pal M. Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges. Biomed Pharmacother. 2017;87:8-19. doi: 10.1016/j.biopha.2016.12.064.
  8. Sinicrope FA. Increasing incidence of early-onset colorectal cancer. N Engl J Med. 2022;386(16):1547-58. doi: 10.1056/NEJMra2200869.
  9. Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. Colorectal cancer. Nat Rev Dis Primers. 2015;1:15065. doi: 10.1038/nrdp.2015.65.
  10. Burton C, Ma Y. Current trends in cancer biomarker discovery using urinary metabolomics: achievements and new challenges. Curr Med Chem. 2019;26(1):5-28. doi: 10.2174/0929867324666170914102236.
  11. Very N, Lefebvre T, El Yazidi-Belkoura I. Drug resistance related to aberrant glycosylation in colorectal cancer. Oncotarget. 2017;9(1):1380-402. doi: 10.18632/oncotarget.22377.
  12. Tumas J, Kvederaviciute K, Petrulionis M, Kurlinkus B, Rimkus A, Sakalauskaite G, et al. Metabolomics in pancreatic cancer biomarkers research. Med Oncol. 2016;33(12):133. doi: 10.1007/s12032-016-0853-6.
  13. Zhao Q, Zhan T, Deng Z, Li Q, Liu Y, Yang S, et al. Glycan analysis of colorectal cancer samples reveals stage-dependent changes in CEA glycosylation patterns. Clin Proteomics. 2018;15:9. doi: 10.1186/s12014-018-9182-4.
  14. Nardy AF, Freire-de-Lima L, Freire-de-Lima CG, Morrot A. The Sweet side of immune evasion: role of glycans in the mechanisms of cancer progression. Front Oncol. 2016;6:54. doi: 10.3389/fonc.2016.00054.
  15. Ferreira JA, Magalhães A, Gomes J, Peixoto A, Gaiteiro C, Fernandes E, et al. Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics. Cancer Lett. 2017;387:32-45. doi: 10.1016/j.canlet.2016.01.044.
  16. Glavey SV, Huynh D, Reagan MR, Manier S, Moschetta M, Kawano Y, et al. The cancer glycome: carbohydrates as mediators of metastasis. Blood Rev. 2015;29(4):269-79. doi: 10.1016/j.blre.2015.01.003.
  17. Cummings RD, Pierce JM. The challenge and promise of glycomics. Chem Biol. 2014;21(1):1-15. doi: 10.1016/j.chembiol.2013.12.010.
  18. Brooks S, Dwek M, Schumacher U. Functional and molecular glycobiology. Garland Science. 1st ed. London: Taylor & Francis Group; 2023.p.298. Available at:
  19. Fu C, Zhao H, Wang Y, Cai H, Xiao Y, Zeng Y, et al. Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. HLA. 2016;88(6):275-86. doi: 10.1111/tan.12900.
  20. Guo H, Abbott KL. Functional impact of tumor-specific N-linked glycan changes in breast and ovarian cancers. Adv Cancer Res. 2015;126:281-303. doi: 10.1016/bs.acr.2014.11.006.
  21. Wang S, Yin D, Wang W, Shen X, Zhu JJ, Chen HY, et al. Targeting and imaging of cancer cells via monosaccharide-imprinted fluorescent nanoparticles. Sci Rep. 2016;6:22757. doi: 10.1038/srep22757.
  22. Blanas A, Sahasrabudhe NM, Rodríguez E, van Kooyk Y, van Vliet SJ. Fucosylated antigens in cancer: an alliance toward tumor progression, metastasis, and resistance to chemotherapy. Front Oncol. 2018;8:39. doi: 10.3389/fonc.2018.00039.
  23. Yan X, Lin Y, Liu S, Aziz F, Yan Q. Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of breast cancer. Biomed Pharmacother. 2015;70:299-304. doi: 10.1016/j.biopha.2014.12.048.
  24. Li Y, Sun Z, Liu B, Shan Y, Zhao L, Jia L. Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer. Cell Death Dis. 2017;8(6):e2892. doi: 10.1038/cddis.2017.281.
  25. Kumar S, Saxena M, Srinivas K, Singh VK. Fucose: A biomarker in grading of oral cancer. Natl J Maxillofac Surg. 2015;6(2):176-9. doi: 10.4103/0975-5950.183869.
  26. Schneider M, Al-Shareffi E, Haltiwanger RS. Biological func­tions of fucose in mammals. Glycobiology. 2017;27:601-18. doi:10.1093/glycob/cwx034.
  27. Manchil PR, Joy ET, Kiran MS, Sherubin JE, Khan MF, Aravind BS. Correlation of serum levo-fucose levels as a biomarker with tumor node metastasis staging in oral cancer patients. J Pharm Bioallied Sci. 2016;8(Suppl 1):S147-S150. doi: 10.4103/0975-7406.191946.
  28. Aziz F, Gao W, Yan Q. Fucosyltransferase-4 and Oligosaccharide Lewis Y antigen as potentially correlative biomarkers of Helicobacter pylori CagA associated gastric cancer. Pathol Oncol Res. 2017;23(1):173-9. doi: 10.1007/s12253-016-0122-1.
  29. Haq S, Sambi M, Qorri B, Mendonza N, SzewczukMR. Aber-rant sialic acid expression and its role in regulating metasta-sis in colorectal cancer. Adv Res Gastroenterol Hepatol. 2017;7(2):22-6. doi:10.19080/ARGH.2017.07.555707.
  30. Chou FC, Chen HY, Kuo CC, Sytwu HK. Role of galectins in tumors and in clinical immunotherapy. Int J Mol Sci. 2018;19(2):430. doi: 10.3390/ijms19020430.
  31. Łukaszewicz-Zając M, Mroczko B. Circulating biomarkers of colorectal cancer (CRC)-their utility in diagnosis and prognosis. J Clin Med. 2021;10(11):2391. doi: 10.3390/jcm10112391.
  32. Munkley J. Aberrant sialylation in cancer: therapeutic opportunities. Cancers (Basel). 2022;14(17):4248. doi: 10.3390/cancers14174248.
  33. Abbasi Natajomrani R, Qujeq D, Hosseini V, Hajihosseini R. Serum alpha-(1, 3)-fucosyltransferase IV, copper, and zinc levels in patients with colorectal cancer and healthy controls. Kermanshah Univ Med Sci. 2020;24(4):e107028. doi10.5812/jkums.107028.
  34. Kononova S, Litvinova E, Vakhitov T, Skalinskaya M, Sitkin S. Acceptive immunity: the role of fucosylated glycans in human host-microbiome interactions. Int J Mol Sci. 2021;22(8):3854. doi: 10.3390/ijms22083854.
  35. Sethi MK, Fanayan S. Mass spectrometry-based N-glycomics of colorectal cancer. Int J Mol Sci. 2015;16(12):29278-304. doi: 10.3390/ijms161226165.
  36. Büll C, Stoel MA, den Brok MH, Adema GJ. Sialic acids sweeten a tumor's life. Cancer Res. 2014;74(12):3199-204. doi: 10.1158/0008-5472.CAN-14-0728.
  37. Peng C, Wallwiener M, Rudolph A, Ćuk K, Eilber U, Celik M, et al. Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer. Int J Cancer. 2016;138(10):2499-509. doi: 10.1002/ijc.29975.
  38. Khan FAT, Chandak R, Nayyar AS, Chandran A, Nachiappan S, Reddy GS. Serum l-fucose levels as a potential biomarker in the early detection of oral potentially malignant epithelial lesions and oral squamous cell carcinoma: An original research article. J Curr Oncol. 2019;2(2):53-60. doi: 10.4103/jco.jco_9_19.
  39. Guruaribam VD, Sarumathi T. Relevance of serum and salivary sialic acid in oral cancer diagnostics. J Cancer Res Ther. 2020;16(3):401-4. doi: 10.4103/jcrt.JCRT_512_19.
  40. Abbasi Natajomrani R, Qujeq D, Hosseini V, Hajihosseini R. Evaluation of L-fucose and Sialic Acid Levels in Patients With Colorectal Cancer and Control Subject. Res Mol Med. 2020; 8(3):147-52. doi:10.32598/rmm.8.3.609.7.
  41. Ruvolo PP. Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta. 2016;1863(3):427-37. doi: 10.1016/j.bbamcr.2015.08.008.
  42. Nejat Pish-Kenari F, Qujeq D, Maghsoudi H. Some of the effective factors in the pathogenesis of gastro-oesophageal reflux disease. J Cell Mol Med. 2018;22(12):6401-4. doi: 10.1111/jcmm.13939.
  43. Dobie C, Skropeta D. Insights into the role of sialylation in cancer progression and metastasis. Br J Cancer 2021;124:76–90. doi:10.1038/s41416-020-01126-7.
  44. Sciacchitano S, Lavra L, Morgante A, Ulivieri A, Magi F, De Francesco GP, et al. Galectin-3: one molecule for an alphabet of diseases, from A to Z. Int J Mol Sci. 2018;26;19(2):379. doi: 10.3390/ijms19020379.
  45. Wang Y, Liu S, Tian Y, Wang Y, Zhang Q, Zhou X, Meng X, et al. Prognostic role of galectin-3 expression in patients with solid tumors: a meta-analysis of 36 eligible studies. Cancer Cell Int. 2018 3;18:172. doi: 10.1186/s12935-018-0668-y.
  46. Radziejewska I. Galectin-3 and epithelial MUC1 mucin-interactions supporting cancer development. Cancers (Basel). 2023;15(10):2680. doi: 10.3390/cancers15102680.
  47. Wu KL, Chen HH, Pen CT, Yeh WL, Huang EY, Hsiao CC, et al. Circulating galectin-1 and 90K/Mac-2BP correlated with the tumor stages of patients with colorectal cancer. Biomed Res Int. 2015;2015:306964. doi: 10.1155/2015/306964.
  48. Abbasinatajomrani R, Qujeq D, Hajihosseini R, Hosseini V, Kazemi Veisari A, Hoznian K. Evaluation of galactin-3 levels in patients with colorectal cancer and control subjects. Intl J Cancer Oncol. 2019;6(2):26-32. doi :10.15436/2377-0902.19.2571.
  49. Hara A, Niwa M, Noguchi K, Kanayama T, Niwa A, Matsuo M, et al. Galectin-3 as a next-generation biomarker for detecting early stage of various diseases. Biomolecules. 2020;10(3):389. doi: 10.3390/biom10030389.
  50. Liu FT, Stowell SR. The role of galectins in immunity and infection. Nat Rev Immunol. 2023;23(8):479-94. doi: 10.1038/s41577-022-00829-7.
  51. Vladoiu MC, Labrie M, St-Pierre Y. Intracellular galectins in cancer cells: potential new targets for therapy (Review). Int J Oncol. 2014;44(4):1001-14. doi: 10.3892/ijo.2014.2267.
  52. Niang DGM, Gaba FM, Diouf A, Hendricks J, Diallo RN, Niang MDS, et al. Galectin-3 as a biomarker in breast neoplasms: Mechanisms and applications in patient care. J Leukoc Biol. 2022;112(5):1041-52. doi: 10.1002/JLB.5MR0822-673R.
  53. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177-93. doi: 10.3322/caac.21395.
  54. Amos-Landgraf JM, Heijmans J, Wielenga MC, Dunkin E, Krentz KJ, Clipson L, et al. Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones. Proc Natl Acad Sci U S A. 2014;111(46):16514-9. doi: 10.1073/pnas.1323064111.
  55. Bouras E, Papandreou C, Tzoulaki I, Tsilidis KK. Endogenous sex steroid hormones and colorectal cancer risk: a systematic review and meta-analysis. Discov Oncol. 2021;12(1):8. doi: 10.1007/s12672-021-00402-z.
  56. Roshan MH, Tambo A, Pace NP. The role of testosterone in colorectal carcinoma: pathomechanisms and open questions. EPMA J. 2016;7(1):22. doi: 10.1186/s13167-016-0071-5.
  57. Abbasi Natajomrani R, Qujeq D, Hajihosseini R, Hosseini V. Serum lipid profile and steroid hormone levels in patients with colorectal cancer. Hormozgan Med J. 2021;25(1):9-13. doi: 10.5812/hmj.102085.
  58. Butler EN, Zhou CK, Curry M, McMenamin Ú, Cardwell C, Bradley MC, et al. Testosterone therapy and cancer risks among men in the SEER-Medicare linked database. Br J Cancer. 2023;128(1):48-56. doi: 10.1038/s41416-022-02019-7.
  59. Ząbczyńska M, Link-Lenczowski P, Pocheć E. Glycosylation in autoimmune diseases. Adv Exp Med Biol. 2021;1325:205-18. doi: 10.1007/978-3-030-70115-4_10.
  60. Caiazza F, Ryan EJ, Doherty G, Winter DC, Sheahan K. Estrogen receptors and their implications in colorectal carcinogenesis. Front Oncol. 2015;5:19. doi: 10.3389/fonc.2015.00019.
  61. Lehnen N, Hallek M. Sex-specific differences of special tumor diseases. [In German] Inn Med (Heidelb). 2023;64(8):717-26. doi: 10.1007/s00108-023-01551-9.