University of Oulu

Khatun M, Urpilainen E, Ahtikoski A, Arffman RK, Pasanen A, Puistola U, Tapanainen JS, Andersson LC, Butzow R, Loukovaara M and Piltonen TT (2021) Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer. Pathol. Oncol. Res. 27:1609936. doi: 10.3389/pore.2021.1609936

Low expression of stanniocalcin 1 (STC-1) protein is associated with poor clinicopathologic features of endometrial cancer

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Author: Khatun, Masuma1; Urpilainen, Elina1; Ahtikoski, Anne2,3;
Organizations: 1Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
2Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland
3Department of Pathology, Turku University Hospital, Turku, Finland
4Department of Pathology, University of Helsinki, Helsinki, Finland
5Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Frontiers Media, 2021
Publish Date: 2021-11-01


Stanniocalcin-1 (STC-1) is a glycoprotein hormone involved in diverse biological processes, including regulation of calcium phosphate homeostasis, cell proliferation, apoptosis, inflammation, oxidative stress responses, and cancer development. The role of STC-1 in endometrial cancer (EC) is yet to be elucidated. In this study, we investigated the protein expression pattern of STC-1 in a tissue microarray (TMA) cohort of hysterectomy specimens from 832 patients with EC. We then evaluated the prognostic value of STC-1 expression regarding the clinicopathologic features and patients survival over a period of 140 months. Our results revealed that in EC tissue samples, STC-1 is mainly localized in the endometrial epithelium, although some expression was also observed in the stroma. Decreased STC-1 expression was associated with factors relating to a worse prognosis, such as grade 3 endometrioid tumors (p = 0.030), deep myometrial invasion (p = 0.003), lymphovascular space invasion (p = 0.050), and large tumor size (p = 0.001). Moreover, STC-1 expression was decreased in tumors obtained from obese women (p = 0.014) and in women with diabetes mellitus type 2 (DMT2; p = 0.001). Interestingly, the data also showed an association between DNA mismatch repair (MMR) deficiency and weak STC-1 expression, specifically in the endometrial epithelium (p = 0.048). No association was observed between STC-1 expression and disease-specific survival. As STC-1 expression was particularly low in cases with obesity and DMT2 in the TMA cohort, we also evaluated the correlation between metformin use and STC-1 expression in an additional EC cohort that only included women with DMT2 (n = 111). The analysis showed no difference in STC-1 expression in either the epithelium or the stroma in women undergoing metformin therapy compared to metformin non-users. Overall, our data may suggest a favorable role for STC-1 in EC behavior; however, further studies are required to elucidate the detailed mechanism and possible applications to cancer treatment.

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Series: Pathology & oncology research
ISSN: 1219-4956
ISSN-E: 1532-2807
ISSN-L: 1219-4956
Volume: 27
Article number: 1609936
DOI: 10.3389/pore.2021.1609936
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Helsinki University Hospital research funds, The Sigrid Juselius Foundation, Academy of Finland.
Copyright information: © 2021 Khatun, Urpilainen, Ahtikoski, Arffman, Pasanen, Puistola, Tapanainen, Andersson, Butzow, Loukovaara and Piltonen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.