Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer

被引:8
作者
Khatun, Masuma [1 ]
Urpilainen, Elina [1 ]
Ahtikoski, Anne [2 ,3 ]
Arffman, Riikka K. [1 ]
Pasanen, Annukka [4 ]
Puistola, Ulla [1 ]
Tapanainen, Juha S. [1 ,5 ,6 ]
Andersson, Leif C. [4 ]
Butzow, Ralf [4 ]
Loukovaara, Mikko [5 ,6 ]
Piltonen, Terhi T. [1 ]
机构
[1] Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit,Med Res Ctr, Oulu, Finland
[2] Univ Oulu, Oulu Univ Hosp, Dept Pathol, Oulu, Finland
[3] Turku Univ Hosp, Dept Pathol, Turku, Finland
[4] Univ Helsinki, Dept Pathol, Helsinki, Finland
[5] Helsinki Univ Hosp, Dept Obstet & Gynaecol, Helsinki, Finland
[6] Univ Helsinki, Helsinki, Finland
基金
芬兰科学院;
关键词
stanniocalcin-1; uterine cancer; type 2 diabetes mellitus; disease-specific survival; endometrioid carcinoma; metformin; RENAL ISCHEMIA/REPERFUSION INJURY; ELEVATED EXPRESSION; GENE-EXPRESSION; METFORMIN; CARCINOMA; BIOMARKER; INVASION; CELLS;
D O I
10.3389/pore.2021.1609936
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 68 条
[1]   Stanniocalcin-1 expression in normal human endometrium and dysregulation in endometriosis [J].
Aghajanova, Lusine ;
Altmae, Signe ;
Kasvandik, Sergo ;
Salumets, Andres ;
Stavreus-Evers, Anneli ;
Giudice, Linda C. .
FERTILITY AND STERILITY, 2016, 106 (03) :681-+
[2]   Preoperative biopsy and intraoperative tumor diameter predict lymph node dissemination in endometrial cancer [J].
AlHilli, Mariam M. ;
Podratz, Karl C. ;
Dowdy, Sean C. ;
Bakkum-Gamez, Jamie N. ;
Weaver, Amy L. ;
McGree, Michaela E. ;
Kumar, Sanjeev ;
Keeney, Gary L. ;
Cliby, William A. ;
Mariani, Andrea .
GYNECOLOGIC ONCOLOGY, 2013, 128 (02) :294-299
[3]   Expression of Stanniocalcin 1 as a Potential Biomarker of Gastric Cancer [J].
Arigami, Takaaki ;
Uenosono, Yoshikazu ;
Ishigami, Sumiya ;
Hagihara, Takahiko ;
Haraguchi, Naoto ;
Matsushita, Daisuke ;
Yanagita, Shigehiro ;
Nakajo, Akihiro ;
Okumura, Hiroshi ;
Hokita, Shuichi ;
Natsugoe, Shoji .
ONCOLOGY, 2012, 83 (03) :158-164
[4]   Current recommendations and recent progress in endometrial cancer [J].
Brooks, Rebecca A. ;
Fleming, Gini F. ;
Lastra, Ricardo R. ;
Lee, Nita K. ;
Moroney, John W. ;
Son, Christina H. ;
Tatebe, Ken ;
Veneris, Jennifer L. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2019, 69 (04) :258-279
[5]   Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy [J].
Cantrell, Leigh A. ;
Zhou, Chunxiao ;
Mendivil, Alberto ;
Malloy, Kimberly M. ;
Gehrig, Paola A. ;
Bae-Jump, Victoria L. .
GYNECOLOGIC ONCOLOGY, 2010, 116 (01) :92-98
[6]   Mammalian stanniocalcins and cancer [J].
Chang, ACM ;
Jellinek, DA ;
Reddel, RR .
ENDOCRINE-RELATED CANCER, 2003, 10 (03) :359-373
[7]   Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways [J].
Chang, Ming-Cheng ;
Chen, Chi-An ;
Chen, Pao-Jen ;
Chiang, Ying-Cheng ;
Chen, Yu-Li ;
Mao, Tsui-Lien ;
Lin, Han-Wei ;
Chiang, Wen-Hsien Lin ;
Cheng, Wen-Fang .
BIOCHEMICAL JOURNAL, 2012, 442 :293-302
[8]   Type 2 diabetes [J].
Chatterjee, Sudesna ;
Khunti, Kamlesh ;
Davies, Melanie J. .
LANCET, 2017, 389 (10085) :2239-2251
[9]   Role of stanniocalcin-1 in breast cancer [J].
Chen, Fengxia ;
Zhang, Zhicai ;
Pu, Feifei .
ONCOLOGY LETTERS, 2019, 18 (04) :3946-3953
[10]   Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation [J].
Deol, HK ;
Varghese, R ;
Wagner, GF ;
DiMattia, GE .
ENDOCRINOLOGY, 2000, 141 (09) :3412-3421