Abstract
Introduction. Stomach cancer in Russia occupies the 4th place among most frequent malignant neoplasms, after tumors of the lung, breast and colon. The search for new diagnostic and prognostic markers of this pathology is an urgent task of modern molecular oncology.
The purpose of the study is a comprehensive analysis of the content of soluble forms of galectin-3, haptoglobin, as well as pro-angiogenic molecules VEGF, sVEGFR1 and sVEGFR2 in patients with gastric cancer.
Material and methods. The study included plasma and serum samples from 60 patients with gastric cancer and from 32 healthy donors. The concentrations of galectin-3, haptoglobin, as well as VEGF, sVEGFR1 and sVEGFR2 were determined using ELISA. The Mann-Whitney test was used to analyze the statistically significant differences in independent groups. Correlation analysis was performed using the Spearman rank correlation coefficient. Overall survival was analyzed by constructing survival curves using the Kaplan–Meier method. Differences were considered statistically significant at p<0.05.
Results. The data of a complex comparative study of the content of soluble forms of galectin-3, haptoglobin, as well as VEGF, sVEGFR1 and sVEGFR2 are presented. The diagnostic significance of galectin-3 and haptoglobin was determined. The study showed that the content of galectin-3 and haptoglobin was statistically significantly lower in the group of healthy donors compared to patients with gastric cancer. Further we showed that the content of galectin-3 and haptoglobin is associated with the localization of the tumor in the stomach. Statistically significant correlations were found between the soluble forms of some of the studied markers, indicating the presence of independent mechanisms of their regulation in gastric cancer, which may explain the ambiguous clinical significance for this type of tumor.
Conclusion. The results will help to better understand the biology of gastric cancer and improve the efficiency of its diagnostics and therapy.
Authors and affiliations
O.V. Kovaleva(1), N.N. Zybina(2), A.N. Gratchev(1), V.L. Chang(3), N.A. Ognerubov(3), I.S. Stilidi(1), N.E. Kushlinskii(1)
1-N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia,
Kashirskoye shosse 23, Moscow, 115520, Russion Federation;
2-A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine of the Ministry of Emergency Situations of Russia,
st. Academician Lebedeva, 4/2, St. Petersburg, 194044, Russian Federation;
3-Medical Institute of Derzhavin Tambov State University, Russian Federation,
392036, Central Federal District, Tambov Region, Tambov, st. Internatsional’naya, 33
References
De Oliveira F.L., Gatto M., Bassi N., Luisetto R., Ghirardello A., Punzi L. et al. Galectin-3 in autoimmunity and autoimmune diseases. Exp Biol Med (Maywood). 2015; 240 (8): 1019–28. https://doi.org/10.1177/1535370215593826
Newlaczyl A.U., Yu L.G. Galectin-3--a jack-of-all-trades in cancer. Cancer letters. 2011; 313 (2): 123–8. https://doi.org/10.1016/j.canlet.2011.09.003
Colnot C., Fowlis D., Ripoche M.A., Bouchaert I., Poirier F. Embryonic implantation in galectin 1/galectin 3 double mutant mice. Dev Dyn. 1998; 211 (4): 306–13. https://doi.org/10.1002/(SICI)1097-0177(199804)211:4<306::AID-AJA2>3.0.CO;2-L
Dumic J., Dabelic S., Flogel M. Galectin-3: an open-ended story. Biochimica et biophysica acta. 2006; 1760 (4): 616–35. https://doi.org/10.1016/j.bbagen.2005.12.020
Sano H., Hsu D.K., Yu L., Apgar J.R., Kuwabara I., Yamanaka T. et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. Journal of immunology. 2000; 165 (4): 2156–64. https://doi.org/10.4049/jimmunol.165.4.2156
John C.M., Jarvis G.A., Swanson K.V., Leffler H., Cooper M.D., Huflejt M.E. et al. Galectin-3 binds lactosaminylated lipooligosaccharides from Neisseria gonorrhoeae and is selectively expressed by mucosal epithelial cells that are infected. Cellular microbiology. 2002; 4 (10): 649–62. https://doi.org/10.1046/j.1462-5822.2002.00219.x
MacKinnon A.C., Farnworth S.L., Hodkinson P.S., Henderson N.C., Atkinson K.M., Leffler H. et al. Regulation of alternative macrophage activation by galectin-3. Journal of immunology. 2008; 180 (4): 2650–8. https://doi.org/10.4049/jimmunol.180.4.2650
Karlsson A., Christenson K., Matlak M., Bjorstad A., Brown K.L., Telemo E. et al. Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils. Glycobiology. 2009; 19 (1): 16–20. https://doi.org/10.1093/glycob/cwn104
Pugliese G., Iacobini C., Pesce C.M., Menini S. Galectin-3: an emerging all-out player in metabolic disorders and their complications. Glycobiology. 2015; 25 (2): 136–50. https://doi.org/10.1093/glycob/cwu111
Dong R., Zhang M., Hu Q., Zheng S., Soh A., Zheng Y. et al. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). Int. J. Mol. Med. 2018; 41 (2): 599–614. https://doi.org/10.3892/ijmm.2017.3311
Tao L., Jin L., Dechun L., Hongqiang Y., Changhua K., Guijun L. Galectin-3 Expression in Colorectal Cancer and its Correlation with Clinical Pathological Characteristics and Prognosis. Open Med (Wars). 2017; 12: 226–30. https://doi.org/10.1515/med-2017-0032
Bresalier R.S., Byrd J.C., Tessler D., Lebel J., Koomen J., Hawke D. et al. A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer. Gastroenterology. 2004; 127 (3): 741–8. https://doi.org/10.1053/j.gastro.2004.06.016
Cheng D., Liang B., Li Y. Serum galectin-3 as a potential marker for gastric cancer. Med Sci Monit. 2015; 21: 755–60. https://doi.org/10.12659/MSM.892386
Tas F., Bilgin E., Tastekin D., Erturk K., Duranyildiz D. Clinical Significance of Serum Galectin-3 Levels in Gastric Cancer Patients. J. Gastrointest Cancer. 2016; 47 (2): 182–6. https://doi.org/10.1007/s12029-016-9817-5
Subhash V.V., Ho B. Galectin 3 acts as an enhancer of survival responses in H. pylori-infected gastric cancer cells. Cell Biol Toxicol. 2016; 32 (1): 23–35. https://doi.org/10.1007/s10565-016-9315-3
Sato S., Ohike N., Enosawa T., Sato M., Imataka H., Wada Y. et al. Clinicopathologic Significance of Galectin-3 Expression Patterns in Gastric Cancer Patients. The Showa University Journal of Medical Sciences. 2009; 21 (1): 45–53. https://doi.org/10.15369/sujms.21.45
Markowska A.I., Liu F.T., Panjwani N. Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response. The Journal of experimental medicine. 2010; 207 (9): 1981–93. https://doi.org/10.1084/jem.20090121
D’Haene N., Sauvage S., Maris C., Adanja I., Le Mercier M., Decaestecker C. et al. VEGFR1 and VEGFR2 involvement in extracellular galectin-1- and galectin-3-induced angiogenesis. PloS one. 2013; 8 (6): e67029. https://doi.org/10.1371/journal.pone.0067029