Plasma AXIN1 expression exhibit negative correlations with inflammatory biomarkers and is associated with gastrointestinal symptoms in endometriosis

Dihm,Katharina; Ek,Malin; Roth,Bodil; Ohlsson,Bodil

doi:10.3892/br.2020.1282

Plasma AXIN1 expression exhibit negative correlations with inflammatory biomarkers and is associated with gastrointestinal symptoms in endometriosis

Authors:
- Katharina Dihm
- Malin Ek
- Bodil Roth
- Bodil Ohlsson
View Affiliations

Affiliations: Department of Internal Medicine, Skane University Hospital, Lund University, 205 02 Malmo, Sweden
Published online on: February 28, 2020 https://doi.org/10.3892/br.2020.1282
Pages: 211-221
Copyright: © Dihm et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The cytoplasmic protein AXIN1 is involved in the Wnt signalling pathway and its expression is increased in patients with endometriosis compared with healthy controls. The aim of the present cross‑sectional study was to further assess the levels of AXIN1 and other inflammatory biomarkers in patients with endometriosis. Patients with laparoscopy‑verified endometriosis were recruited (n=172) and completed a questionnaire regarding socioeconomic factors, lifestyle habits and medical history. Plasma AXIN1 and high‑sensitivity C‑reactive protein (hs‑CRP) levels were analysed by ELISA. The levels of calprotectin were determined in the faeces, and the haemoglobin concentration and number of erythrocytes, leukocytes and platelets were determined in the blood in a subgroup of 64 patients during clinical routine procedures. F‑calprotectin expression was detected in 18 women (28.1%), who had more severe constipation and more frequently experienced incomplete evacuation when defecating, and 5 women (7.8%) exhibited elevated levels. P‑AXIN1 levels were higher in patients who received hormonal treatment, and correlated inversely with faecal‑calprotectin levels (P=0.003), B‑haemoglobin levels (P=0.030) and the numbers of B‑erythrocytes (P=0.033) and B‑platelets (P=0.017), but were not correlated with hs‑CRP levels (P=0.818). Higher levels of AXIN1 were associated with the duration of the gastrointestinal symptoms and with diarrhoea, constipation, vomiting and nausea and the intestinal symptoms' effect on quality of life, and tended to be associated with the duration of endometriosis. Hs‑CRP expression was not associated with the clinical characteristics or symptoms of endometriosis, but higher levels were associated with obesity (P=0.002) and hormonal treatment (P=0.011). In conclusion, P‑AXIN1 expression was negatively correlated with certain inflammatory biomarkers and was positively associated with gastrointestinal symptoms. P‑AXIN1 levels were increased in patients who received hormonal treatment, highlighting the importance of obtaining native samples for future studies regarding its role in the development and presentation of endometriosis. However, hs‑CRP and other studied biomarkers seemed to be of no value for the assessment and diagnosis of endometriosis.

View Figures

View References

1	Eskenazi B and Warner ML: Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 24:235–258. 1997.PubMed/NCBI View Article : Google Scholar
2	Creed J, Maggrah A, Reguly B and Harbottle A: Mitochondrial DNA deletions accurately detect endometriosis in symptomatic females of child-bearing age. Biomark Med. 13:291–306. 2019.PubMed/NCBI View Article : Google Scholar
3	Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M and Wei J: Endometriosis. Endocr Soc. 40:1048–1079. 2019.PubMed/NCBI View Article : Google Scholar
4	Viganò D, Zara F and Usai P: Irritable bowel syndrome and endometriosis: New insights for old diseases. Dig Liver Dis. 50:213–219. 2018.PubMed/NCBI View Article : Google Scholar
5	Giudice LC and Kao LC: Endometriosis. Lancet. 364:1789–1799. 2004.PubMed/NCBI View Article : Google Scholar
6	Fassbender A, Burney RO, O DF, D'Hooghe T and Giudice L: Update on biomarkers for the detection of endometriosis. Biomed Res Int. 2015(130854)2015.PubMed/NCBI View Article : Google Scholar
7	Ek M, Roth B, Engström G and Ohlsson B: AXIN1 in plasma or serum is a potential new biomarker for endometriosis. Int J Mol Sci. 20(189)2019.PubMed/NCBI View Article : Google Scholar
8	Kikuchi A: Roles of axin in the Wnt signalling pathway. Cell Signal. 11:777–788. 1999.PubMed/NCBI View Article : Google Scholar
9	MacDonald BT, Tamai K and He X: Wnt/beta-catenin signaling: Components, mechanisms, and diseases. Dev Cell. 17:9–26. 2009.PubMed/NCBI View Article : Google Scholar
10	Shi J, Chi S, Xue J, Yang J, Li F and Liu X: Emerging role and therapeutic implication of Wnt signaling pathways in autoimmune diseases. J Immunol Res. 2016(9392132)2016.PubMed/NCBI View Article : Google Scholar
11	Hod K, Dickman R, Sperber A, Melamed S, Dekel R, Ron Y, Halpern Z, Berliner S and Maharshak N: Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable bowel syndrome. Neurogastroenterol Motil. 23:1105–1110. 2011.PubMed/NCBI View Article : Google Scholar
12	Pletikosic S, Plavsic I, Hauser G and Tkalcic M: Fecal calprotectin and serum chromogranin A as potential biomarkers of irritable bowel syndrome symptom severity. Med Hypotheses. 85:339–342. 2015.PubMed/NCBI View Article : Google Scholar
13	Thubert T, Santulli P, Marcellin L, Menard S, M'Baye M, Streuli I, Borghese B, de Ziegler D and Chapron C: Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis: Prospective study of 834 patients. Am J Obstet Gynecol. 210:533.e1–533.e10. 2014.PubMed/NCBI View Article : Google Scholar
14	Ni Bhriain H, Trovik J, Wik E, Stefansson IM, Akslen LA, Salvesen HB and Staff AC: Plasma calprotectin concentrations in women with endometrial carcinoma. Gynecol Oncol. 114:491–495. 2009.PubMed/NCBI View Article : Google Scholar
15	Kostakis ID, Cholidou KG, Kallianidis K, Perrea D and Antsaklis A: The role of calprotectin in obstetrics and gynecology. Eur J Obstet Gynecol Reprod Biol. 151:3–9. 2010.PubMed/NCBI View Article : Google Scholar
16	Yang Z, Clark N and Park KT: Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children. Clin Gastroenterol Hepatol. 12:253–262, e2. 2014.PubMed/NCBI View Article : Google Scholar
17	Mumolo MG, Bertani L, Ceccarelli L, Laino G, Di Fluri G, Albano E, Tapete G and Costa F: From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol. 24:3681–3694. 2018.PubMed/NCBI View Article : Google Scholar
18	World Medical Association: World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 310: 2191-2194, 2013.
19	Ek M, Roth B, Nilsson PM and Ohlsson B: Characteristics of endometriosis: A case-cohort study showing elevated IgG titers against the TSH receptor (TRAb) and mental comorbidity. Eur J Obstet Gynecol Reprod Biol. 231:8–14. 2018.PubMed/NCBI View Article : Google Scholar
20	Bengtsson M, Ohlsson B and Ulander K: Development and psychometric testing of the visual analogue scale for irritable bowel syndrome (VAS-IBS). BMC Gastroenterol. 7(16)2007.PubMed/NCBI View Article : Google Scholar
21	Labmedicin Skåne Analysportalen. Available online: http://www.analysportalen-labmedicin.skane.se/.
22	Bengtsson M, Hammar O, Mandl T and Ohlsson B: Evaluation of gastrointestinal symptoms In different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS). BMC Gastroenterol. 11(122)2011.PubMed/NCBI View Article : Google Scholar
23	World Health Organization. Global databae on body mass index. Available from: http://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi.
24	Moparthi L and Koch S: Wnt signaling in intestinal inflammation. Differentiation. 108:24–32. 2019.PubMed/NCBI View Article : Google Scholar
25	Clevers H and Nusse R: Wnt/β-catenin signaling and disease. Cell. 149:1192–1205. 2012.PubMed/NCBI View Article : Google Scholar
26	Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, Mohammed S, Heck AJ, Maurice MM, Mahmoudi T and Clevers H: Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 149:1245–1256. 2012.PubMed/NCBI View Article : Google Scholar
27	Arend RC, Londoño-Joshi AI, Straughn JM Jr and Buchsbaum DJ: The Wnt/β-catenin pathway in ovarian cancer: A review. Gynecol Oncol. 131:772–779. 2013.PubMed/NCBI View Article : Google Scholar
28	Silva-García O, Valdez-Alarcón JJ and Baizabal-Aguirre VM: The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria. Mediators Inflamm. 2014(310183)2014.PubMed/NCBI View Article : Google Scholar
29	Katoh M: Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β-catenin signaling activation (Review). Int J Mol Med. 42:713–725. 2018.PubMed/NCBI View Article : Google Scholar
30	Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S and Kikuchi A: Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBOJ. 17:1371–1384. 1998.PubMed/NCBI View Article : Google Scholar
31	Song X, Wang S and Li L: New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein Cell. 5:186–193. 2014.PubMed/NCBI View Article : Google Scholar
32	Mukherjee A, Dhar N, Stathos M, Schaffer DV and Kane RS: Understanding how Wnt influences destruction complex activity and β-catenin dynamics. iScience. 6:13–21. 2018.PubMed/NCBI View Article : Google Scholar
33	Matsuzaki S, Botchorishvili R, Pouly JL and Canis M: Targeting the Wnt/beta-pathway in endometriosis: A potentially effective approach for treatment and prevention. Mol Cell Ther. 2(36)2014.PubMed/NCBI View Article : Google Scholar
34	Zhang L, Xiong W, Xiong Y, Liu H and Liu Y: 17 β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis. Mol Hum Reprod. 22:526–535. 2016.PubMed/NCBI View Article : Google Scholar
35	Issa B, Onon TS, Agrawal A, Shekhar C, Morrs J, Hamdy S and Whorwell PJ: Visceral hypersensitivity in endometriosis: A new target for treatment? Gut. 61:3667–3672. 2012.PubMed/NCBI View Article : Google Scholar
36	Nilholm C, Roth B and Ohlson B: A dietary intervention with reduction of starch and sucrose leads to reduced gastrointestinal and extra-intestinal symptoms in IBS patients. Nutrients. 11: pii(E1662)2019.PubMed/NCBI View Article : Google Scholar
37	Daryabor G, Kabelitz D and Kalantar K: An update on immune dysregulation in obesity-related insulin resistance. Scand J Immunol. 89(e12747)2019.PubMed/NCBI View Article : Google Scholar
38	Røseth AG, Schmidt PN and Fagerhol MK: Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol. 34:50–54. 1999.PubMed/NCBI View Article : Google Scholar
39	Andréasson K, Scheja A, Saxne T, Ohlsson B and Hesselstrand R: Faecal calprotectin: A biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med. 270:50–57. 2011.PubMed/NCBI View Article : Google Scholar
40	Ek M, Roth B, Valentin L, Nordengren J and Ohlsson B: Autoantibodies common in patients with gastrointestinal diseases are not found in patients with endometriosis: A cross-sectional study. Eur J Obstet Gynecol Reprod Biol. 240:370–374. 2019.PubMed/NCBI View Article : Google Scholar
41	Hirsch M, Begum MR, Paniz É, Barker C and Davis CJ: Diagnosis and management of endometriosis: A systematic review of international and national guidelines. BJOG. 125:556–564. 2018.PubMed/NCBI View Article : Google Scholar