Vol 60, No 4 (2022)
Original paper
Published online: 2022-12-19

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FUCA2 and TSTA3 expression in gastric cancer: candidate biomarkers of malignant transformation

Michael Williames Leal Quirino1, Amanda Pinheiro de Barros Albuquerque1, Maria de Fátima Deodato de Souza1, Antônio Felix da Silva Filho1, Mário Rino Martins2, Maira Galdino da Rocha Pitta1, Michelly Cristiny Pereira1, Moacyr Jesus Barreto de Melo1
Pubmed: 36583336
Folia Histochem Cytobiol 2022;60(4):335-343.

Abstract

Introduction. Aberrant fucosylation is closely related to malignant transformation, cancer detection, and evaluation of treatment efficacy. The fucosylation process requires GDP-L-fucose, fucosyltransferases, and fucosidases. In gastric cancer (GC), fucosylation alterations were associated with tumor formation, metastasis inhibition, and multi-drug resistance. It is not clear whether tissue-specific transplantation antigen P35B (TSTA3) and alpha-L-fucosidase 2 (FUCA2) have any effect on the development of GC.

Materials and methods. We used immunohistochemistry to assess the expression of TSTA3 and FUCA2 in 71 gastric adenocarcinoma samples and their relationship with clinicopathological parameters.

Results. TSTA3 expression was associated with lower histological grade I and II (P = 0.0120) and intestinal type Lauren classification (P = 0.0120). TSTA3 immunopositivity could predict Lauren’s classification. Analysis of mRNA expression in GC validation cohorts corroborates the significant TSTA3 association with histological grade observed in our study. However, no associations were found between TSTA3 staining and overall survival. FUCA2 expression was markedly increased in GC tissues compared with non-tumoral tissues (P < 0.0001) and was associated with surgical staging III and IV (P = 0.0417) and advanced histological grade tumor states (P = 0.0125).

Conclusions. Alterations of FUCA2 and TSAT3 immunoexpression could lay the basis for future studies using cell glycosylation as a biomarker for the planning of therapeutic strategy in primary gastric cancer.

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References

  1. Choi YJ, Kim N. Gastric cancer and family history. Korean J Intern Med. 2016; 31(6): 1042–1053.
  2. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–249.
  3. Bonelli P, Borrelli A, Tuccillo FM, et al. Precision medicine in gastric cancer. World J Gastrointest Oncol. 2019; 11(10): 804–829.
  4. Padró M, Cobler L, Garrido M, et al. Down-regulation of FUT3 and FUT5 by shRNA alters Lewis antigens expression and reduces the adhesion capacities of gastric cancer cells. Biochim Biophys Acta. 2011; 1810(12): 1141–1149.
  5. 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): 173–179.
  6. Wu J, Qin H, Li T, et al. Characterization of site-specific glycosylation of secreted proteins associated with multi-drug resistance of gastric cancer. Oncotarget. 2016; 7(18): 25315–25327.
  7. Zhu J, Wang Y, Yu Y, et al. Aberrant fucosylation of glycosphingolipids in human hepatocellular carcinoma tissues. Liver Int. 2014; 34(1): 147–160.
  8. Munkley J, Elliott DJ. Hallmarks of glycosylation in cancer. Oncotarget. 2016; 7(23): 35478–35489.
  9. Magalhães A, Duarte HO, Reis CA. Aberrant glycosylation in cancer: a novel molecular mechanism controlling metastasis. Cancer Cell. 2017; 31(6): 733–735.
  10. Moriwaki K, Noda K, Nakagawa T, et al. A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation. Glycobiology. 2007; 17(12): 1311–1320.
  11. Natoni A, Macauley MS, O'Dwyer ME. Targeting selectins and their ligands in cancer. Front Oncol. 2016; 6: 93.
  12. Muinelo-Romay L, Villar-Portela S, Cuevas Alvarez E, et al. α(1,6)Fucosyltransferase expression is an independent prognostic factor for disease-free survival in colorectal carcinoma. Hum Pathol. 2011; 42(11): 1740–1750.
  13. Tonetti M, Sturla L, Bisso A, et al. Synthesis of GDP-L-fucose by the human FX protein. J Biol Chem. 1996; 271(44): 27274–27279.
  14. Zhou H, Sun L, Li J, et al. The crystal structure of human GDP-L-fucose synthase. Acta Biochim Biophys Sin (Shanghai). 2013; 45(9): 720–725.
  15. Villar-Portela S, Muinelo-Romay L, Cuevas E, et al. FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer. Histopathology. 2013; 63(2): 174–186.
  16. Croce MV, Price MR, Segal-Eiras A. Association of a alpha1 acidic glycoprotein and squamous cell carcinoma of the head and neck. Pathol Oncol Res. 2001; 7(2): 111–117.
  17. Noda K, Miyoshi E, Gu J, et al. Relationship between elevated FX expression and increased production of GDP-L-fucose, a common donor substrate for fucosylation in human hepatocellular carcinoma and hepatoma cell lines. Cancer Res. 2003; 63(19): 6282–6289.
  18. Kizuka Y, Nakano M, Yamaguchi Y, et al. An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3. Cell Chem Biol. 2017; 24(12): 1467–1478.e5.
  19. Niittymäki J, Mattila P, Renkonen R. Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII. APMIS. 2006; 114(7-8): 539–548.
  20. Yang J, Kong P, Yang J, et al. High TSTA3 Expression as a Candidate Biomarker for Poor Prognosis of Patients With ESCC. Technol Cancer Res Treat. 2018; 17: 1533033818781405.
  21. de Carlos A, Rodrõ JE, Vin JE. Cell surface human a - L -fucosidase. 2001; 3331: 3321–3331.
  22. Sulzenbacher G, Bignon C, Nishimura T, et al. Crystal structure of Thermotoga maritima alpha-L-fucosidase. Insights into the catalytic mechanism and the molecular basis for fucosidosis. J Biol Chem. 2004; 279(13): 13119–13128.
  23. You J, Lin S, Jiang T. Origins and evolution of the α-L-Fucosidases: from bacteria to metazoans. Front Microbiol. 2019; 10: 1756.
  24. Delacadena M, Fernandez J, Decarlos A, et al. Low levels of alpha-L-fucosidase activity in colorectal cancer are due to decreased amounts of the enzymatic protein and are related with Dukes' stage. Int J Oncol. 1996; 9(4): 747–754.
  25. Ayude D, Páez de la Cadena M, Cordero OJ, et al. Clinical interest of the combined use of serum CD26 and alpha-L-fucosidase in the early diagnosis of colorectal cancer. Dis Markers. 2003; 19(6): 267–272.
  26. Fawzy Montaser M, Amin Sakr M, Omar Khalifa M. Alpha-L-fucosidase as a tumour marker of hepatocellular carcinoma. Arab J Gastroenterol. 2012; 13(1): 9–13.
  27. Cheng TC, Tu SH, Chen LC, et al. Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface. Oncotarget. 2015; 6(25): 21283–21300.
  28. Bonin S, Parascandolo A, Aversa C, et al. Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients. Oncotarget. 2018; 9(20): 15228–15238.
  29. Xing H, Qiu H, Ding X, et al. Clinical performance of α-L-fucosidase for early detection of hepatocellular carcinoma. Biomark Med. 2019; 13(7): 545–555.
  30. Togayachi A, Iwaki J, Kaji H, et al. Glycobiomarker, fucosylated short-form secretogranin III levels are increased in serum of patients with small cell lung carcinoma. J Proteome Res. 2017; 16(12): 4495–4505.
  31. Waidely E, Al-Youbi AO, Bashammakh AS, et al. Alpha-l-Fucosidase immunoassay for early detection of hepatocellular carcinoma. Anal Chem. 2017; 89(17): 9459–9466.
  32. Doherty M, Theodoratou E, Walsh I, et al. Plasma N-glycans in colorectal cancer risk. Sci Rep. 2018; 8(1): 8655.
  33. Kim KH, Lee SY, Hwang H, et al. Direct monitoring of fucosylated glycopeptides of alpha-fetoprotein in human serum for early hepatocellular carcinoma by liquid chromatography-tandem mass spectrometry with immunoprecipitation. Proteomics Clin Appl. 2018; 12(6): e1800062.
  34. Yazawa S, Yokobori T, Kaira K, et al. A new enzyme immunoassay for the determination of highly sialylated and fucosylated human α-acid glycoprotein as a biomarker of tumorigenesis. Clin Chim Acta. 2018; 478: 120–128.
  35. Keeley TS, Yang S, Lau E. The Diverse Contributions of Fucose Linkages in Cancer. Cancers (Basel). 2019; 11(9).
  36. de Souza Md, da Silva Filho AF, de Barros Albuquerque AP, et al. Overexpression of UDP-glucose 4-epimerase is associated with differentiation grade of gastric cancer. Dis Markers. 2019; 2019: 6325326.
  37. Dimitrova N, Zamudio JR, Jong RM, et al. The CBio Cancer Genomics. PLoS One. 2017; 32: 736–740.
  38. Contessa JN, Bhojani MS, Freeze HH, et al. Inhibition of N-linked glycosylation disrupts receptor tyrosine kinase signaling in tumor cells. Cancer Res. 2008; 68(10): 3803–3809.
  39. Sun Y, Liu X, Zhang Q, et al. Oncogenic potential of TSTA3 in breast cancer and its regulation by the tumor suppressors miR-125a-5p and miR-125b. Tumour Biol. 2016; 37(4): 4963–4972.
  40. Yang J, Kong P, Yang J, et al. High TSTA3 expression as a candidate biomarker for poor prognosis of patients with ESCC. Technol Cancer Res Treat. 2018; 17: 1533033818781405.
  41. Villar-Portela S, Muinelo-Romay L, Cuevas E, et al. FX enzyme and GDP-L-Fuc transporter expression in colorectal cancer. Histopathology. 2013; 63(2): 174–186.
  42. Norton PA, Mehta AS. Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review. World J Gastroenterol. 2019; 25(23): 2947–2960.
  43. Park S, Lim JM, Chun JN, et al. Altered expression of fucosylation pathway genes is associated with poor prognosis and tumor metastasis in non‑small cell lung cancer. Int J Oncol. 2020; 56(2): 559–567.
  44. Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer. 2015; 15(9): 540–555.
  45. Listinsky JJ, Siegal GP, Listinsky CM. The emerging importance of α-L-fucose in human breast cancer: a review. Am J Transl Res. 2011; 3(4): 292–322.
  46. Shan M, Yang D, Dou H, et al. Fucosylation in cancer biology and its clinical applications. Prog Mol Biol Transl Sci. 2019; 162: 93–119.
  47. Song Q, Lv X, Ru Yi, et al. Circulating exosomal gastric cancer-associated long noncoding RNA1 as a noninvasive biomarker for predicting chemotherapy response and prognosis of advanced gastric cancer: A multi-cohort, multi-phase study. EBioMedicine. 2022; 78: 103971.
  48. Gan Y, Liang Q, Song X. Diagnostic value of alpha-L-fucosidase for hepatocellular carcinoma: a meta-analysis. Tumour Biol. 2014; 35(5): 3953–3960.
  49. Shuang Z, Mao Y, Lin G, et al. Alpha-L-fucosidase serves as a prognostic indicator for intrahepatic cholangiocarcinoma and inhibits its invasion capacity. Biomed Res Int. 2018; 2018: 8182575.
  50. Xu XC, Zhang YH, Zhang WB, et al. MicroRNA-133a functions as a tumor suppressor in gastric cancer. J Biol Regul Homeost Agents. 2014; 28(4): 615–624.
  51. Gan Y, Liang Q, Song X. Diagnostic value of alpha-L-fucosidase for hepatocellular carcinoma: a meta-analysis. Tumour Biol. 2014; 35(5): 3953–3960.
  52. Cheng TC, Tu SH, Chen LC, et al. Down-regulation of α-L-fucosidase 1 expression confers inferior survival for triple-negative breast cancer patients by modulating the glycosylation status of the tumor cell surface. Oncotarget. 2015; 6(25): 21283–21300.
  53. Liu TW, Ho CW, Huang HH, et al. Role for alpha-L-fucosidase in the control of Helicobacter pylori-infected gastric cancer cells. Proc Natl Acad Sci U S A. 2009; 106(34): 14581–14586.
  54. Yu X, Zhang R, Yang T, et al. Alpha-l-fucosidase: a novel serum biomarker to predict prognosis in early stage esophageal squamous cell carcinoma. J Thorac Dis. 2019; 11(9): 3980–3990.



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