Abstract
Relevance. Ectopic secretion, which occurs in the early stages of tumor development, is not only one of the first signs of a neoplasm, but can also indicate the severity of the oncological process.
Purpose of the study: To evaluate the possibility of using the expression of sorcin, histamine and caldesmon to predict distant metastases of gastric, prostate and lung carcinomas.
Material and methods. The medical histories of 98 people and histological material from carcinomas of the stomach, prostate and lungs were studied. Using the method of immunohistochemistry, data were obtained on the relative area of expression of molecular markers in tumor cells – sorcin, histamine and caldesmon at various stages of tumor differentiation. Discriminant analysis was used to predict distant metastasis of carcinomas.
Results. It was found that the relative expression of sorcin, histamine and caldesmon is statistically significantly lower in tumors with a high degree of differentiation (G1–G2) than in low-grade ones (G3–G4). Moreover, the presence of metastases was registered only for tumors with a low degree of differentiation. The relative expression area of sorcin, histamine and caldesmon had a high correlation with tumor differentiation. To predict the occurrence of distant metastases based on the expression of biological markers, discriminant functions were generated. Evaluation of the resulting discriminant model showed the correctness of the forecast in 94.8% of cases.
Conclusion. The study found that high levels of the relative area of sorcin, histamine and caldesmon indicate low differentiation of adenocarcinomas in the stomach, prostate gland and lungs. These biological markers can be used to predict distant metastases for adequate selection of further treatment tactics.
Authors and affiliations
U.A. Novak-Bobarykina(4), M.A. Dokhov(1, 2), Yu.S. Krylova(1, 3), T.V. Kvetnaya(4), M.A. Paltsev(5, 6)
1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovsky Ave., 2–4, St. Petersburg, 191036, Russian Federation;
2-Federal State Budgetary Educational Institution of Higher Education St. Petersburg State Pediatric Medical University
of the Ministry of Health of Russia, st. Litovskaya 2, St. Petersburg, 194100, Russian Federation;
3-Federal State Budgetary Educational Institution of Higher Education “First St. Petersburg State Medical University Academician
named after I.P. Pavlov” Ministry of Health of Russia, st. Lev Tolstoy, 6–8, St. Petersburg, 197022, Russian Federation;
4-Autonomous scientific non-profit organization of higher education Research Center “St. Petersburg
Institute of Bioregulation and Gerontology”, Dynamo Ave., 3, St. Petersburg, 197110, Russian Federation;
5-Federal State Budgetary Educational Institution of Higher Education “Moscow State University
named after. M.V. Lomonosov”, Leninskie Gory, 1, Moscow, 119234, Russian Federation;
6-Federal State Autonomous Educational Institution of Higher Education “Russian Peoples’ Friendship University
named after Patrice Lumumba”, st. Miklouho-Maklaya, 6, Moscow, 117198, Russian Federation
References
Stecklein S.R., Sharma P. Last but not least: antibody-drug conjugates in hormone receptor-positive metastatic breast cancer. Ann Oncol. 2020; 31 (12): 1594–6. https://doi.org/10.1016/j.annonc.2020.10.001.
Truong T.H., Lange C.A. Deciphering Steroid Receptor Crosstalk in Hormone-Driven Cancers. Endocrinology. 2018; 159 (12): 3897–07. https://doi.org/10.1210/en.2018-00831.
Neschadim A., Summerlee A.J., Silvertown J.D. Targeting the relaxin hormonal pathway in prostate cancer. Int. J. Cancer. 2015; 137 (10): 2287–95. https://doi.org/10.1002/ijc.29079.
Reznikov A. Hormonal impact on tumor growth and progression. Exp Oncol. 2015; 37 (3): 162–72.
Nualart F., Los Angeles Garcia M., Medina R.A., Owen G.I. Glucose transporters in sex steroid hormone related cancer. Curr Vasc Pharmacol. 2009; 7 (4): 534–48. https://doi.org/10.2174/157016109789043928.
Ceresoli G.L., De Vincenzo F., Sauta M.G., Bonomi M., Zucali P.A. Role of chemotherapy in combination with hormonal therapy in first-line treatment of metastatic hormone-sensitive prostate cancer. Q J. Nucl Med Mol Imaging. 2015; 59 (4): 374–80.
Bodmer A., Castiglione-Gertsch M. Role of hormonal manipulations in patients with hormone-sensitive metastatic breast cancer. Eur. J. Cancer. 2011; 47 (3): 28–37. https://doi.org/10.1016/S0959-8049(11)70144-7.
Deli T., Orosz M., Jakab A. Hormone Replacement Therapy in Cancer Survivors – Review of the Literature. Pathol Oncol Res. 2020; 26 (1): 63–78. https://doi.org/10.1007/s12253-018-00569-x.
Subramani R., Nandy S.B., Pedroza D.A., Lakshmanaswamy R. Role of Growth Hormone in Breast Cancer. Endocrinology. 2017; 158 (6): 1543–55. https://doi.org/doi:10.1210/en.2016-1928.
Saeger W., Schnabel P.A., Komminoth P. Grading neuroendokriner Tumoren. Pathologe. 2016; 37: 304–13. https://doi.org/doi:10.1007/s00292-016-0186-4.
Shabnam B., Padmavathi G., Banik K., Girisa S., Monisha J., Sethi G., Fan L., Wang L., Mao X., Kunnumakkara A.B. Sorcin a Potential Molecular Target for Cancer Therapy. Transl Oncol. 2018; 11 (6): 1379–89. https://doi.org/10.1016/j.tranon.2018.08.015.
Mao J., Ling F., Gislaine Pires Sanches J., Yu X., Wei Y., Zhang J. The potential mechanism of action of Sorcin and its interacting proteins. Clin Chim Acta. 2020; 510: 741–5. https://doi.org/10.1016/j.cca.2020.09.011.
Gupta K., Sirohi V.K., Kumari S., Shukla V., Manohar M., Popli P., Dwivedi A. Sorcin is involved during embryo implantation via activating VEGF/PI3K/Akt pathway in mice. J. Mol. Endocrinol. 2018; 60 (2): 119–32. https://doi.org/10.1530/JME-17-0153.
Ilari A., Fiorillo A., Poser E., Lalioti V.S., Sundell G.N., Ivarsson Y., Genovese I., Colotti G. Structural basis of Sorcin-mediated calcium-dependent signal transduction. Sci Rep. 2015; 5: 16828. https://doi.org/10.1038/srep16828.
Johansson S., Landstrom M., Henriksson R. Alterations of tumor cells, stroma and apoptosis in rat prostatic adenocarcinoma following treatment with histamine, interleukin-2 and irradiation. Anticancer Res. 1999; 19: 1961–70.
Rivera E.S., Davio C.A., Venturino A. Histamine receptors in an experimental mammary carcinoma. Biomed. Pharmacother. 1994; 48: 346–99.
Bartholeyns J., Bouclier M. Involvement of histamine in growth of mouse and rat tumors: Antitumoral properties of monofluoromethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase. Cancer Res. 1984; 44: 639–645.
Huang Z.,Guo B.-J., Xiang J.-J. Zhongguo bingli shengli zazhi (КНР). Clin. J. Pathphysiol. 2003; 19 (7): 1000–10.
Hirst D.G., Flitney F.W. The physiological importance and therapeutic potencial of nitric oxide in the tumorassociated vasculature. In: Tumor angiogenesis. Oxford Univ. Press. 1997; 153–67.
Zheng P.-P., Hop W.C., SillevisSmitt P.A.E. et al. Low-molecular weight caldesmon as a potential serum marker for glioma. Clinical Cancer Research. 2005; 11 (12): 4388–92. https://doi.org/10.1158/1078-0432.ccr-04-2512
Cheng Q., Tang A., Wang Z. et al. CALD1 modulates gliomas progression via facilitating tumor angiogenesis. Cancers. 2021; 13 (11): 2705. https://doi.org/10.3390/cancers13112705
Li C., Yang F., Wang R. et al. CALD1 promotes the expression of PD-L1 in bladder cancer via the JAK/stat signaling pathway. Annals of Translational Medicine. 2021; 9 (18): 1441. https://doi.org/10.21037/atm-21-4192
Li Y., Shan Z., Liu C. et al. MicroRNA-294 promotes cellular proliferation and motility through the PI3K/akt and JAK/STAT pathways by upregulation of NRAS in bladder cancer. Biochemistry (Moscow). 2017; 82 (4): 474–82. https://doi.org/10.1134/s0006297917040095
Helfman D.M., Levy E.T., Berthier C. et al. Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Molecular Biology of the Cell. 1999; 10 (10): 3097–112. https://doi.org/10.1091/mbc.10.10.3097