Serum galectin-3 and -9 and clinical and morphological characteristics of colorectal cancer

O.V. Kovaleva; Yu.B. Kuzmin; A.A. Alferov; A.N. Gratchev; S.O. Kochkina; L.V. Akulenko; N.N. Zybina; O.O. Janushevich; Z.Z. Mammadli; I.S. Stilidi; N.E. Kushlinskii

doi:10.18127/j20700997-202303-03

Serum galectin-3 and -9 and clinical and morphological characteristics of colorectal cancer

O.V. Kovaleva¹, Yu.B. Kuzmin², A.A. Alferov³, A.N. Gratchev⁴, S.O. Kochkina⁵, L.V. Akulenko⁶, N.N. Zybina⁷, O.O. Janushevich⁸, Z.Z. Mammadli⁹, I.S. Stilidi¹⁰, N.E. Kushlinskii¹¹

research article UDC 616.34-002+577.112 Pages: 17-24 doi.org/10.18127/j20700997-202303-03

^1,4,5,9,10 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia (Moscow, Russia)
^2,3,11 N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia (Moscow, Russia); A.I. Evdokimov Moscow State University of Medicine and Dentistry
^6,8 A.I. Evdokimov Moscow State University of Medicine and Dentistry
⁷ A.M. Nikiforov All-Russian Center for Emergency and Radiation Medicine Ministry of Emergency Situations of Russia (St. Petersburg, Russia)

Keywords: Galectin-9 colorectal cancer blood serum prognosis

Abstract

Formulation of the problem. Galectins are galactoside-binding lectin involved in numerous cellular processes including apoptosis, adhesion, migration, tumor growth, invasion, and metastasis.

The purpose of the work is a comparative study of the content of galectin-3 and -9 in the blood serum of healthy donors and patients with colorectal cancer (CRC) in association with the main clinical and morphological characteristics of the disease and prognosis.

Results. Serum galectin-9 levels fluctuated widely in 140 examined patients with CRC, however, the median content of the marker in the blood serum of patients with CRC was significantly higher (11.1 ng/ml) than in the control group of healthy donors (9.61 ng/ml; р=0.05). At the same time, the data of ROC analysis do not allow the use of determining the levels of serum galectin-9 in the diagnosis of CRC.

A more significant difference was noted for galectin-3, namely, its median content in the healthy donor group was 8.2 (6.0-10.17) ng/ml, while in the group of patients with CRC it was 12.6 (9.4-16.2) ng/ml (p<0.0001). The study did not reveal significant associations with the main clinical and morphological characteristics of CRC. Correlation analysis between the content of galectin-3 and galectin-9 revealed a strong direct correlation between the content of these proteins in the circulation of both CRC patients (r=0.391; p<0.0001) and healthy donors (r=0.700; p=0.0006).A significant relationship was found between low values of galectin-9 (<11.1 ng/ml) and poor prognosis of overall survival.

Practical significance. Baseline pre-treatment serum levels of galectin-9 in CRC patients can be used as a prognostic marker in assessing overall survival: serum galectin-9 levels <11.1 ng/mL indicate a poor survival prognosis.

Received: 20.06.2023
Approved after review: 07.07.2023
Accepted: 01.08.2023

How to cite

Ковалёва О.В., Кузьмин Ю.Б., Алфёров А.А., Грачёв А.Н., Кочкина С.О., Акуленко Л.В., Зыбина Н.Н., Янушевич О.О., Мамедли З.З., Стилиди И.С., Кушлинский Н.Е. Сывороточные галектины-3 и -9 и клинико-морфологические характеристики колоректального рака // Технологии живых систем. 2023. T. 20. № 3. С. 17-24. DOI: https://doi.org/10.18127/j20700997-202303-03

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[1] Compagno D., Tiraboschi C., Garcia J.D., Rondon Y., Corapi E., Velazquez C., Laderach D.J. Galectins as Checkpoints of the Immune System in Cancers, Their Clinical Relevance, and Implication in Clinical Trials. Biomolecules. 2020. V. 10. № 5. http://doi.org/ 10.3390/biom10050750

[2] de Oliveira F.L., Gatto M., Bassi N., Luisetto R., Ghirardello A., Punzi L., Doria A. Galectin-3 in autoimmunity and autoimmune diseases. Exp. Biol. Med. (Maywood). 2015. V. 240. № 8. P. 1019–1028. http://doi.org/10.1177/1535370215593826

[3] Zubieta M.R., Furman D., Barrio M., Bravo A.I., Domenichini E., Mordoh J. Galectin-3 expression correlates with apoptosis of tumor-associated lymphocytes in human melanoma biopsies. Am. J. Pathol. 2006. V. 168. № 5. P. 1666–1675. http://doi.org/10.2353/ajpath.2006.050971

[4] Melief S.M., Visconti V.V., Visser M., van Diepen M., Kapiteijn E.H., van den Berg J.H., Haanen J.B., Smit V.T., Oosting J., van der Burg S.H., Verdegaal E.M. Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature. Cancer Immunol. Res. 2017. V. 5. № 2. P. 170–179. http://doi.org/10.1158/2326-6066.CIR-16-0288

[5] Chen X., Song C.H., Liu Z.Q., Feng B.S., Zheng P.Y., Li P., In S.H., Tang S.G., Yang P.C. Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine. Allergy. 2011.
V. 66. № 8. P. 1038–1046. http://doi.org/10.1111/j.1398-9995.2011.02585.x

[6] Imaizumi T., Kumagai M., Sasaki N., Kurotaki H., Mori F., Seki M., Nishi N., Fujimoto K., Tanji K., Shibata T., Tamo W., Matsumiya T., Yoshida H., Cui X.F., Takanashi S., Hanada K., Okumura K., Yagihashi S., Wakabayashi K., Nakamura T., Hirashima M., Satoh K. Interferon-gamma stimulates the expression of galectin-9 in cultured human endothelial cells. J. Leukoc. Biol. 2002. V. 72. № 3. P. 486–491.

[7] Morishita A., Oura K., Tadokoro T., Shi T., Fujita K., Tani J., Atsukawa M., Masaki T. Galectin-9 in Gastroenterological Cancer. International Journal of Molecular Sciences. 2023. V. 24. № 7. P. 6174.

[8] Chabot S., Kashio Y., Seki M., Shirato Y., Nakamura K., Nishi N., Nakamura T., Matsumoto R., Hirashima M. Regulation of galectin-9 expression and release in Jurkat T cell line cells. Glycobiology. 2002. V. 12. № 2. P. 111–118. http://doi.org/10.1093/glycob/12.2.111

[9] Oomizu S., Arikawa T., Niki T., Kadowaki T., Ueno M., Nishi N., Yamauchi A., Hattori T., Masaki T., Hirashima M. Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion. PLoS One. 2012. V. 7. № 11. P. e48574. http://doi.org/10.1371/journal.pone.0048574

[10] Merani S., Chen W., Elahi S. The bitter side of sweet: the role of Galectin-9 in immunopathogenesis of viral infections. Rev. Med. Virol. 2015. V. 25. № 3. P. 175–186. http://doi.org/10.1002/rmv.1832

[11] Yasinska I.M., Sakhnevych S.S., Pavlova L., Teo Hansen Selno A., Teuscher Abeleira A.M., Benlaouer O., Goncalves Silva I., Mosimann M., Varani L., Bardelli M., Hussain R., Siligardi G., Cholewa D., Berger S.M., Gibbs B.F., Ushkaryov Y.A., Fasler-Kan E., Klenova E., Sumbayev V.V. The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer. Front. Immunol. 2019. V. 10. P. 1594. http://doi.org/10.3389/fimmu.2019.01594

[12] Sakaki M., Oka N., Nakanishi R., Yamaguchi K., Fukumori T., Kanayama H.O. Serum level of galectin-3 in human bladder cancer. J. Med. Invest. 2008. V. 55. № 1-2. P. 127–132. http://doi.org/10.2152/jmi.55.127

[13] Kovaleva O.V., Zybina N.N., Grachev A.N., Chang V.L., Ognerubov N.A., Stilidi I.S., Kushlinskiy N.E. Galektin-3. gaptoglobin i proangiogennyye faktory pri rake zheludka. Molekulyarnaya meditsina. 2022. T. 20. № 4. S. 28–34. https://doi.org/10.29296/ 24999490-2022-04-05 (in Russian).

[14] Kuzmin Yu.B., Alferov A.A., Prishchep P.L., Korotkova E.A., Kovaleva O.V., Tsarapayev P.V., Kuznetsov I.N., Sokolov N.Yu., Bulycheva I.V., Gershteyn E.S., Varfolomeyeva S.R., Stilidi I.S., Kushlinskiy N.E. Galektin-3 i kontrolnaya tochka immuniteta sVISTA v syvorotke krovi bolnykh opukholyami kostey. Klinicheskaya laboratornaya diagnostika. 2023. T. 68. № 2. S. 74–80. https://doi.org/10.51620/0869-2084-2023-68-2-74-80 (in Russian).

[15] Cymbaluk-Ploska A., Gargulinska P., Kwiatkowski S., Pius-Sadowska E., Machalinski B. Could Galectin 3 Be a Good Prognostic Factor in Endometrial Cancer?. Diagnostics (Basel). 2020. V. 10. № 9. http://doi.org/10.3390/diagnostics10090635

[16] Wang C., Zhou X., Ma L., Zhuang Y., Wei Y., Zhang L., Jin S., Liang W., Shen X., Li C., Wang Y., Pang L. Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis. Pathol. Res. Pract. 2019. V. 215. № 10. P. 152612. http://doi.org/10.1016/j.prp.2019.152612

[17] Wdowiak K., Gallego-Colon E., Francuz T., Czajka-Francuz P., Ruiz-Agamez N., Kubeczko M., Grochola I., Wybraniec M.T., Chudek J., Wojnar J. Increased serum levels of Galectin-9 in patients with chronic lymphocytic leukemia. Oncol. Lett. 2019. V. 17. № 1. P. 1019–1029. http://doi.org/10.3892/ol.2018.9656

[18] Okoye I., Xu L., Motamedi M., Parashar P., Walker J.W., Elahi S. Galectin-9 expression defines exhausted T cells and impaired cytotoxic NK cells in patients with virus-associated solid tumors. J. Immunother. Cancer. 2020. V. 8. № 2. Р. е001849. http://doi.org/10.1136/jitc-2020-001849

[19] Wang K., Chen Z., Wu R., Yin J., Fan M., Xu X. Prognostic Role of High Gal-9 Expression in Solid Tumours: a Meta-Analysis. Cell Physiol. Biochem. 2018. V. 45. № 3. P. 993–1002. http://doi.org/10.1159/000487294

[20] He Y., Jia K., Dziadziuszko R., Zhao S., Zhang X., Deng J., Wang H., Hirsch F.R., Zhou C. Galectin-9 in non-small cell lung cancer. Lung Cancer. 2019. V. 136. P. 80–85. http://doi.org/10.1016/j.lungcan.2019.08.014

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