IL-8 AND WISP1 IN THE MOLECULAR CHARACTERISTICS OF MALIGNANT ASCITES IN OVARIAN CANCER



Cite item

Full Text

Abstract

An unfavorable prognosis for ovarian cancer is associated with metastasis to the peritoneum and the formation of malignant ascites, which contains factors affecting the growth and survival of tumor cells. Molecular and functional analysis of ascites provides information both for clinical diagnosis and for understanding the mechanisms of progression and resistance in ovarian cancer.

The aim of the study was to evaluate the levels of IL-8 and WISP-1 in the acellular portion of ascites in advanced ovarian cancer.

In 30 patients diagnosed with ascitic ovarian cancer stage III-IV according to FIGO, before treatment, the level of IL-8 (Kit A-8762, Interleukin-8-ELISA-BEST, JSC Vector-Best, Russia) and WISP1 (Kit SEG895Hu Cloud-Clone Corp., China) (pg/ml). Based on the results of the effectiveness of chemotherapy according to the TP scheme, all patients were divided into the following groups: without relapse, relapse-free period up to 6 months - early relapse and progression during chemotherapy. Statistical processing was carried out using Statistica 13. Analysis of patient progression-free time was carried out using the Cox regression method, and the patient survival function was assessed using the Kaplan-Meier method (Jamovi 2.4.14).

We found that the level of IL-8 in the acellular part of malignant ascites in ovarian cancer in patients without relapse is significantly lower than in the early relapse group (176.58 (139.68-217.01) pg/ml versus 320.43 pg/ml ml (250.49-369.81), p=0.019). The level of WISP-1 was significantly increased in the acellular part of ascites only in patients with progression during chemotherapy (980.51 (796.61-1524.15) pg/ml versus 770.55 (500.60-1254.90) pg/ml in patients without relapse and 764.09 (581.55-823.38) pg/ml in patients with relapse). We found a positive strong Pearson correlation between IL-8 and WISP-1 in ascites in a group of patients without relapse (r=0.783, p=0.012). In the multivariate version of Cox regression, the risk of relapse increases by 1.01 (1.01-1.02, p=0.001) times with an increase in the level of IL-8 in the acellular part of ascites. When IL-8 levels in the acellular portion of ascites are above 225 pg/ml, the median progression-free time in patients with advanced ovarian cancer is 11.7 [5.2-18.2, 95%CI] months.

Thus, increased levels of IL-8 and WISP-1 in malignant ascites in ovarian cancer are associated with a shorter progression-free time. IL-8 in malignant ascites activates Wnt/β-catenin signaling in advanced ovarian cancer.

About the authors

Tatyana V. Abakumova

Ulyanovsk State University

Email: taty-abakumova@yandex.ru
ORCID iD: 0000-0001-7559-5246
SPIN-code: 8564-4253
Scopus Author ID: 37103623900

Doctor of Biological Sciences, Professor at the Department of Physiology and Pathophysiology, Leading Researcher, Scientific Research Technological Institute named S.P. Kapitsa, UlSU

Russian Federation, 2, Arch.Livchak Str., Ulyanovsk, 432017, Russia

Dinara R. Dolgova

Ulyanovsk State University

Email: dolgova.dinara@yandex.ru
ORCID iD: 0000-0001-5475-7031
SPIN-code: 7093-3564
Scopus Author ID: 55378365200

Candidate of Biological Sciences, assistant professor at the Department of Physiology and Pathophysiology, Senior Researcher, Director of the Research Medical and Biological Center, Scientific Research Technological Institute named S.P. Kapitsa, UlSU

Russian Federation, 2, Arch.Livchak Str., Ulyanovsk, 432017, Russia

Sabina S. Pirmamedova

Ulyanovsk State University;
Regional Clinical Oncology Center of Ulyanovsk

Email: sabina-doc@inbox.ru
ORCID iD: 0000-0003-3245-4472
SPIN-code: 3050-0178
Scopus Author ID: 56529650400

Candidate of Medical Sciences, doctor of the Department Oncogynecology of the Regional Clinical Oncological Center, Ulyanovsk, Senior Researcher, Scientific Research Technological Institute named S.P. Kapitsa, UlSU

Russian Federation, 2, Arch.Livchak Str., 432017, Ulyanovsk; 90, September 12th Str., 432017, Ulyanovsk

Inna I. Antoneeva

Ulyanovsk State University; Regional Clinical Oncology Center of Ulyanovsk

Email: aii72@mail.ru
ORCID iD: 0000-0002-1525-2070
SPIN-code: 5305-5108
Scopus Author ID: 6504605612

Doctor of medical sciences, Professor, Professor at the department of Oncology and Radiology, UlSU, Head of the Department of Oncogynecology of the Regional Clinical Oncological Center, Ulyanovsk

Russian Federation, 2, Arch.Livchak Str., 432017, Ulyanovsk; 90, September 12th Str., 432017, Ulyanovsk

Snezhanna O. Gening

LLC BestDoctor

Author for correspondence.
Email: sgening@bk.ru
SPIN-code: 2496-2467
Scopus Author ID: 55151451500

Ph.D., oncologist LLC BestDoctor

Réunion, 27 b, Vyatskaya Str., build. 15, 121205, Moscow

Inna A. Ivanchenko

Ulyanovsk State University

Email: in.iwan4enko@yandex.ru
ORCID iD: 0009-0004-5638-7790

4th year student of the Faculty of Medicine, specialty “General Medicine”, UlSU

Russian Federation, 2, Arch.Livchak Str., Ulyanovsk, 432017, Russia

Tatyana P. Gening

Ulyanovsk State University

Email: Naum-53@yandex.ru
ORCID iD: 0000-0002-5117-1382
SPIN-code: 7285-8939
Scopus Author ID: 6507217338

Doctor of Biological Sciences, Professor, Head of the Department of Physiology and Pathophysiology, UlSU.

Russian Federation, 2, Arch.Livchak Str., Ulyanovsk, 432017, Russia

References

  1. Aleshikova O.I., Antonova I.B., Babaeva N.A. Cytokine profle dynamics in ascites with advanced ovarian cancer // Obstetrics and Gynecology: News, Opinions, Training. 2019. Vol. 7, no. 1, pp. 16–23 (In Russian). doi: 10.24411/2303-9698-2019-11002
  2. Abell S.K., De Courten B., Boyle J.A., Teede H.J. Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus // Int J Mol Sci. 2015. Vol.16, pp.13442–13473. doi: 10.3390/ijms160613442.
  3. Antony F., Deantonio C., Cotella D., Soluri M.F., Tarasiuk O., Raspagliesi F., Adorni F., Piazza S., Ciani Y., Santoro C., Macor P., Mezzanzanica D., Sblattero D. High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids // Oncoimmunology. 2019. Vol.8, no. 9, pp. e1614856. doi: 10.1080/2162402X.2019.1614856.
  4. Barchetta I., Cimini F.A., De Gioannis R., Ciccarelli G., Bertoccini L., Lenzi A., Baroni M.G., Cavallo M.G. Procollagen-III peptide identifies adipose tissue-associated inflammation in type 2 diabetes with or without nonalcoholic liver disease // Diabetes Metab Res Rev. 2018. Vol.34, no. 5, pp. e2998. doi: 10.1002/dmrr.2998.
  5. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA Cancer J Clin. 2018. Vol.68, no. 6, pp. 394-424. doi: 10.3322/caac.21492.
  6. Brigstock D.R. The CCN family: a new stimulus package // J Endocrinol. 2003. Vol.178, pp. 169–175. doi: 10.1677/joe.0.1780169.
  7. Chang A.C., Lien M.Y., Tsai M.H., Hua C.H., Tang C.H. WISP-1 Promotes Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells Via the miR-153-3p/Snail Axis // Cancers (Basel). 2019. Vol.11, no. 12, pp. 1903. doi: 10.3390/cancers11121903.
  8. Jones V.S., Huang R.Y., Chen L.P., Chen Z.S., Fu L., Huang R.P. Cytokines in cancer drug resistance: Cues to new therapeutic strategies // Biochim Biophys Acta. 2016. Vol.1865, no. 2, pp. 255-65. doi: 10.1016/j.bbcan.2016.03.005.
  9. Jun J.I., Lau L.F. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets // Nat Rev Drug Discov. 2011. Vol.10, pp. 945–963. doi: 10.1038/nrd3599.
  10. Krugmann J., Schwarz C.L., Melcher B., Sterlacci W., Ozalinskaite A., Lermann J., Agaimy A., Vieth M. Malignant ascites occurs most often in patients with high-grade serous papillary ovarian cancer at initial diagnosis: a retrospective analysis of 191 women treated at Bayreuth Hospital, 2006-2015 // Arch Gynecol Obstet. 2019. Vol. 299, no. 2, pp. 515-523. doi: 10.1007/s00404-018-4952-9.
  11. Li Y., Wang F., Liu T., Lv N., Yuan X., Li P. WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis // J Ovarian Res. 2022. Vol. 15, no. 1, pp. 94. doi: 10.1186/s13048-022-01016-x.
  12. Rickard B.P., Conrad C., Sorrin A.J., Ruhi M.K., Reader J.C., Huang S.A., Franco W., Scarcelli G., Polacheck W.J., Roque D.M., Del Carmen M.G., Huang H.C., Demirci U., Rizvi I. Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response // Cancers (Basel). 2021. Vol.13, no. 17, pp. 4318. doi: 10.3390/cancers13174318
  13. Tsai H.C., Tzeng H.E., Huang C.Y., Huang Y.L., Tsai C.H., Wang S.W., Wang P.C., Chang A.C., Fong Y.C., Tang C.H. WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma // Cell Death Dis. 2017. Vol. 8, no. 4, pp. e2750. doi: 10.1038/cddis.2016.421.
  14. Wen J., Zhao Z., Huang L, Wang L., Miao Y., Wu J. IL-8 promotes cell migration through regulating EMT by activating the Wnt/β-catenin pathway in ovarian cancer // J Cell Mol Med. 2020. Vol. 24, no. 2, pp. 1588-1598. doi: 10.1111/jcmm.14848.
  15. Wróblewski M., Szewczyk-Golec K., Hołyńska-Iwan I., Wróblewska J., Woźniak A. Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients // Cancers (Basel). 2021. Vol. 13, no. 18, pp. 4702. doi: 10.3390/cancers13184702.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) Abakumova T.V., Dolgova D.R., Pirmamedova S.S., Antoneeva I.I., Gening S.O., Ivanchenko I.A., Gening T.P.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies