Levels of oncofetal proteins in pathological tissues of patients with gastric cancer
https://doi.org/10.31146/1682-8658-ecg-169-9-50-55
Abstract
Aim. Study of levels of CA-19.9, CA-125, CA-72.4 and He-4 in tissues of tumor, peritoneum and omentum in patients with gastric cancer T3–4аN0–3M1 and T3–4аN0–3M0.
Materials and methods. The study included 62 patients: 21 (10♂, 11♀) — gastric cancer T3–4аN0–3M1 and peritoneal metastases; 24 (15♂, 9♀) — gastric cancer T3–4аN0–3M0 without metastases; 17 (6♂, 11♀) — non-cancer patients (controls). Levels of oncofetal proteins were measured by ELISA in tissues of the peritoneum, greater omentum, and gastric tumors (GT).
Results. Levels of practically all studied factors were elevated in tissues of GT, omentum and peritoneum. Levels of He-4 and CA-19.9 in all tissues of patients with advanced cancer increased higher than in the majority of patients without metastases: in GT — respectively by 2.6 and 1.8 times (p<0.05), in the omentum — respectively by 24.4 and 4.8 times, in the peritoneum — respectively by 2.1 and 8.5 times. Omental tissues of patients with advanced cancer showed a higher increase in levels of CA-72.4 and CA-125 as well — by 6.1 and 2.1 times, respectively. A small number of patients with T3–4аN0–3M0 gastric cancer, who had CA-19.9 in the omentum and peritoneum as high as in patients with T3–4аN0–3M1, developed metastases in the corresponding tissues 4–6 months after the study.
Conclusion. The content of oncoprotein markers in tissues of the peritoneum and omentum is one of the factors associated with metastatic characteristics, and CA-19.9 level can serve as an informative laboratory test for the predictive assessment of the further disease development.
About the Authors
O. I. Kit
Rostov Research Institute of Oncology
Russian Federation
Russian Federation
Kit Oleg Ivanovich, General Director, Honored Doctor of the Russian Federation, D. Med. Sc., Professor, Corresponding
Member of RAS, 344037, Rostov-on-Don, Russia
E. M. Frantsiyants
Rostov Research Institute of Oncology
Russian Federation
Frantsiyants Elena Mikhaylovna, Head of Laboratory of Malignant Tumor Pathogenesis Study, D. Biol. Sc., Professor, 344037, Rostov-on-Don, Russia
Russian Federation
Frantsiyants Elena Mikhaylovna, Head of Laboratory of Malignant Tumor Pathogenesis Study, D. Biol. Sc., Professor, 344037, Rostov-on-Don, Russia
I. V. Kaplieva
Rostov Research Institute of Oncology
Russian Federation
Kaplieva Irina Viktorovna, Senior researcher of Laboratory of Malignant Tumor Pathogenesis Study, D. Med. Sc., 344037, Rostov-on-Don, Russia
Russian Federation
Kaplieva Irina Viktorovna, Senior researcher of Laboratory of Malignant Tumor Pathogenesis Study, D. Med. Sc., 344037, Rostov-on-Don, Russia
Yu. A. Gevorkyan
Rostov Research Institute of Oncology
Russian Federation
Gevorkyan Yuryi Artushevich, Head of Department of Abdominal Oncology No.2, D. Med. Sc., Professor, 344037, Rostov-on-Don, Russia
Russian Federation
Gevorkyan Yuryi Artushevich, Head of Department of Abdominal Oncology No.2, D. Med. Sc., Professor, 344037, Rostov-on-Don, Russia
N. V. Soldatkina
Rostov Research Institute of Oncology
Russian Federation
Soldatkina Natalia Vasilevna, Senior researcher of Department of Abdominal Oncology No.2., D. Med. Sc., 344037, Rostov-on-Don, Russia
Russian Federation
Soldatkina Natalia Vasilevna, Senior researcher of Department of Abdominal Oncology No.2., D. Med. Sc., 344037, Rostov-on-Don, Russia
E. A. Dzhenkova
Rostov Research Institute of Oncology
Russian Federation
Dzhenkova Elena Alekseevna, Scientifi c Secretary, D. Biol.Sc., Assistant Professor, 344037, Rostov-on-Don, Russia
Russian Federation
Dzhenkova Elena Alekseevna, Scientifi c Secretary, D. Biol.Sc., Assistant Professor, 344037, Rostov-on-Don, Russia
N. S. Samoylenko
Rostov Research Institute of Oncology
Russian Federation
Samoylenko Nikolay Sergeevich, Postgraduate student of Department of Abdominal Oncology No.2., 344037, Rostov-on-Don, Russia
Russian Federation
Samoylenko Nikolay Sergeevich, Postgraduate student of Department of Abdominal Oncology No.2., 344037, Rostov-on-Don, Russia
Yu. A. Pogorelova
Rostov Research Institute of Oncology
Russian Federation
Pogorelova Yulia Aleksandrovna, Senior researcher of Laboratory of Malignant Tumor Pathogenesis Study, Cand. Biol. Sc., 344037, Rostov-on-Don, Russia
Russian Federation
Pogorelova Yulia Aleksandrovna, Senior researcher of Laboratory of Malignant Tumor Pathogenesis Study, Cand. Biol. Sc., 344037, Rostov-on-Don, Russia
References
1. Kit O. I. Nejroendokrinnye, klinicheskie i molekulyarno-biologicheskie aspekty raka zheludka [Neuroendocrine, clinical and molecular biological aspects of gastric cancer]. Rostov-on-Don, ZAO “Rostizdat”, 2012.
2. Mikuła-Pietrasik J., Uruski P., Tykarski A., Książek K. The peritoneal “soil” for a cancerous “seed”: a comprehensive review of the pathogenesis of intraperitoneal cancer metastases. Cellular and Molecular Life Sciences, 2018, vol.75, no. 3, pp.509–525. http://doi.org/10.1007/s00018–017–2663–1.
3. Paget S. The distribution of secondary growths in cancer of the breast. Lancet, 1889, no.1, pp.571–573. doi: 10.1016/S0140–6736(00)49915–0.
4. Hiratsuka S., Watanabe A., Aburatani H., Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat. Cell. Biol., 2006, no.8, pp. 1369–1375. doi: 10.1038/ncb1507.
5. Tsai J.H., Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev., 2013, no.27, pp.2192–2206. doi: 10.1101/gad.225334.113.
6. Kaplan RN, Rafi i S, Lyden D. Preparing the “soil”: the premetastatic niche. Cancer Res. 2006;66:11089–11093. doi: 10.1158/0008–5472.CAN-06–2407.
7. Shimada H., Noie T., Ohashi M. et al. Clinical significance of serum tumor markers for gastric cancer: A systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer, 2014, no.17, pp.26–33. doi: 10.1007/s10120–013–0259–5.
8. Kim J.H., Jun K. H., Jung H. et al. Prognostic value of preoperative serum levels of five tumor markers (Carcinoembryonic Antigen, CA19–9, Alphafetoprotein, CA72–4, and CA125) in gastric cancer. Hepatogastroenterology, 2014, no.61, pp.863–869.
9. Yu J., Zhang S., Zhao B. Differences and correlation of serum CEA, CA19–9 and CA72–4 in gastric cancer. Mol. Clin. Oncol., 2016, no.4, pp.441–449. doi: 10.3892/mco.2015.712.
10. Zhou H., Dong A., Xia H. et al. Associations between CA19–9 and CA125 levels and human epidermal growth factor receptor 2 overexpression in patients with gastric cancer. Oncologyletters, 2018, vol. 16, no. 1, pp. 1079–1086.
11. Kim D.H., Yun H. Y., Ryu D. H. et al. Preoperative CA 125 is significant indicator of curative resection in gastric cancer patients. World journal of gastroenterology, 2015, vol. 21, no. 4, pp. 1216–1221.
12. Kim D.H., Kim S. M., Hyun J. K. et al. Changes in postoperative recurrence and prognostic risk factors for patients with gastric cancer who underwent curative gastric resection during different time periods. Ann. Surg. Oncol., 2013, no.20, pp. 2317–2327.
13. Bingle L., Singleton V., Bingle C. D. The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene, 2002, no. 21, pp. 2768–73.10.1038/sj.onc.1205363
14. James N.E., Chichester C., Ribeiro J. R. Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer. Frontiers in oncology, 2018, no. 8, p. 124. doi: 10.3389/fonc.2018.00124
15. Moore R.G., McMeekin D.S., Brown A. K. et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol. Oncol., 2009, no.112, pp.40–6.10.1016/j.ygyno.2008.08.031.
16. Bingle L., Cross S. S., High A. S. et al. WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res, 2006, no.7, p. 61.10.1186/1465–9921–7–61
17. LeBleu V.S., Teng Y., O’Connell J.T. et al. Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nature medicine, 2013, no. 19, pp. 227–231.
18. Nagy B. Jr., Krasznai Z. T., Balla H. et al. Elevated human epididymis protein 4 concentrations in chronic kidney disease. Annals of clinical biochemistry, 2012, no. 49, pp. 377–380.
19. Wan J., Wang Y., Cai G. et al. Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease. Oncotarget, 2016, vol.7, no.42, pp.67748–67759.
20. Strimbu K., Tavel J. A. What are biomarkers? Current Opinion in HIV and AIDS, 2010, vol. 5, no. 6, pp. 463–466. doi: 10.1097/COH.0b013e32833ed177.
21. Hanash S.M., Pitteri S. J., Faca V. M. Mining the plasma proteome for cancer biomarkers. Nature, 2008, vol. 452, no. 7187, pp. 571–579.
22. Ludwig J.A., Weinstein J. N. Biomarkers in cancer staging, prognosis and treatment selection. Nature Reviews Cancer, 2005, vol. 5, no. 11, pp. 845–856.
23. Yotsukura S., Mamitsuka H. Evaluation of serum-based cancer biomarkers: a brief review from a clinical and computational viewpoint. Critical Reviews in Oncology/Hematology, 2014, vol. 93, no. 2, pp. 103–115.
24. Kirwan A., Utratna M., O’Dwyer M.E. et al. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics. BioMed research international, 2015, 490531.
25. Lengyel E. Ovarian cancer development and metastasis. Am. J. Pathol., 2010, no. 177, pp. 1053–1064. doi: 10.2353/ajpath.2010.100105.
26. Coccolini F., Gheza F., Lotti M. et al. Peritoneal carcinomatosis. World Journal of Gastroenterology: WJG, 2013, vol. 19, no. 41, pp. 6979–6994. http://doi.org/10.3748/wjg.v19.i41.6979
27. Low R.N. MR imaging of the peritoneal spread of malignancy. Abdom. Imaging., 2007, no. 32, pp. 267–283. doi: 10.1007/s00261–007–9210–8.
28. Nowicka A., Marini F. C., Solley T. N. et al. Human Omental-Derived Adipose Stem Cells Increase Ovarian Cancer Proliferation, Migration, and Chemoresistance. PLoS ONE, 2013, vol. 8, no. 12, e81859.http://doi.org/10.1371/journal.pone.0081859.
29. Gerber S.A., Rybalko V. Y., Bigelow C. E. et al. Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am. J. Pathol., 2006, no. 169, pp. 1739–1752. doi: 10.2353/ajpath.2006.051222.
30. Lambert A.W., Pattabiraman D. R., Weinberg R. A. Emerging Biological Principles of Metastasis. Cell, 2017, vol. 168, no. 4, pp. 670–691.
Review
For citations:
Kit O.I., Frantsiyants E.M., Kaplieva I.V., Gevorkyan Yu.A., Soldatkina N.V., Dzhenkova E.A., Samoylenko N.S., Pogorelova Yu.A. Levels of oncofetal proteins in pathological tissues of patients with gastric cancer. Experimental and Clinical Gastroenterology. 2019;(9):50-55. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-169-9-50-55
Views:
424
Email this article 