BMI‑1 promotes invasion and metastasis in endometrial adenocarcinoma and is a poor prognostic factor Corrigendum in /10.3892/or.2022.8352

Yu,Jing; Chen,Ling; Bao,Zhenhua; Liu,Ying; Liu,Guohong; Li,Fengling; Li,Lianqin

doi:10.3892/or.2020.7539

BMI‑1 promotes invasion and metastasis in endometrial adenocarcinoma and is a poor prognostic factor

Corrigendum in: /10.3892/or.2022.8352

Authors:
- Jing Yu
- Ling Chen
- Zhenhua Bao
- Ying Liu
- Guohong Liu
- Fengling Li
- Lianqin Li
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Affiliations: Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China, Department of Obstetrics and Gynecology, First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang 832001, P.R. China, Department of Oncology, People's Hospital of Haiyang, Haiyang, Shandong 265100, P.R. China, Department of Physical Examination, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China, Department of Obstetrics and Gynecology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China
Published online on: March 10, 2020 https://doi.org/10.3892/or.2020.7539
Pages: 1630-1640
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial adenocarcinoma is one of the most common types of gynecological malignancies and its incidence and mortality rates are increasing. Due to tumor recurrence and metastasis, the overall five‑year survival rate of patients with endometrial adenocarcinoma is shortened. The aim of the present was to investigate the role of the polycomb group protein B‑lymphoma Mo‑MLV insertion region 1 (BMI‑1) in the invasion, metastasis and the epithelial‑mesenchymal transition (EMT) of endometrial adenocarcinoma cells, as well its effects on the prognosis of patients with endometrial adenocarcinoma. Immunohistochemistry was used to examine the expression profile of BMI‑1 in normal and endometrial adenocarcinoma tissues. Western blotting was used to examine the expression levels of BMI‑1 and EMT markers. Kaplan‑Meier plots and a Cox proportional hazards model were used to assess the overall survival. MTT cell viability assays were used to detect the proliferation of endometrial cancer cells. Transwell assays were used to examine cell migration and invasion. Small interfering RNA was used to downregulate BMI‑1 expression levels, to study its effect on EMT. Immunohistochemical and clinicopathological analyses showed that BMI‑1 expression was increased in endometrial adenocarcinoma tissue compared with the normal endometrial tissue (P<0.05). The increased expression levels of BMI‑1 were closely associated with stage, myometrial invasion and lymph node metastasis (P<0.05). Kaplan‑Meier plots and a Cox proportional hazards model showed that increased BMI‑1 expression was associated with a less favorable prognosis [P=0.040, hazards ratio (HR)=1.596] and was associated with late‑stage adenocarcinoma (P=0.006, HR=1.670). Myometrial invasion (P=0.006, HR=1.509) and lymph node metastasis (P=0.004, HR=1.703) were determined to predict a less favorable prognosis. Downregulation of BMI‑1 reduced migration and invasion in endometrial cancer cells in vivo. It was also found that downregulation of BMI‑1 increased the expression levels of the epithelial markers E‑cadherin and keratin, and decreased the expression levels of the mesenchymal markers N‑cadherin, vimentin and the downstream transcription factor, Slug. In conclusion, BMI‑1 expression was correlated with tumor invasion and metastasis, contributing to deep myometrial invasion and lymph node metastasis, and was a poor prognostic factor for endometrial adenocarcinoma.

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1	Sheikh MA, Althouse AD, Freese KE, Soisson S, Edwards RP, Welburn S, Sukumvanich P, Comerci J, Kelley J, LaPorte RE and Linkov F: USA endometrial cancer projections to 2030: Should we be concerned? Future Oncol. 10:2561–2568. 2014. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
3	Kulhan M, Kulhan G, Nayki U, Nayki C, Ulug P, Sipahi M and Yildirim Y: Assessment of clinicopathological features, evaluation of treatment, and prognosis of clear cell and serous papillary endometrial carcinoma. Ginekol Pol. 87:570–574. 2016. View Article : Google Scholar : PubMed/NCBI
4	Dessai SB, Adrash D, Geetha M, Arvind S, Bipin J, Nayanar S, Sachin K, Biji MS and Balasubramanian S: Pattern of care in operable endometrial cancer treated at a rural-based tertiary care cancer center. Indian J Cancer. 53:416–419. 2016.PubMed/NCBI
5	Ouldamer L, Bendifallah S, Body G, Touboul C, Graesslin O, Raimond E, Collinet P, Coutant C, Bricou A, Lavoué V, et al: Incidence, patterns and prognosis of first distant recurrence after surgically treated early stage endometrial cancer: Results from the multicentre FRANCOGYN study group. Eur J Surg Oncol. 45:672–678. 2019. View Article : Google Scholar : PubMed/NCBI
6	Francis SR, Ager BJ, Do OA, Huang YJ, Soisson AP, Dodson MK, Werner TL, Sause WT, Grant JD and Gaffney DK: Recurrent early stage endometrial cancer: Patterns of recurrence and results of salvage therapy. Gynecol Oncol. 154:38–44. 2019. View Article : Google Scholar : PubMed/NCBI
7	Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Rossetti D, Frigerio L and Mariani A: Management of endometrial cancer: Issues and controversies. Eur J Gynaecol Oncol. 37:6–12. 2016.PubMed/NCBI
8	Evans T, Sany O, Pearmain P, Ganesan R, Blann A and Sundar S: Differential trends in the rising incidence of endometrial cancer by type: data from a UK population-based registry from 1994 to 2006. Br J Cancer. 104:1505–1510. 2011. View Article : Google Scholar : PubMed/NCBI
9	Rajasekhar VK and Begemann M: Concise review: Roles of polycomb group proteins in development and disease: A stem cell perspective. Stem Cells. 25:2498–2510. 2007. View Article : Google Scholar : PubMed/NCBI
10	Jiang L, Li J and Song L: Bmi-1, stem cells and cancer. Acta Biochim Biophys Sin (Shanghai). 41:527–534. 2009. View Article : Google Scholar : PubMed/NCBI
11	Beà S, Tort F, Pinyol M, Puig X, Hernández L, Hernández S, Fernandez PL, van Lohuizen M, Colomer D and Campo E: BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res. 61:2409–2412. 2001.PubMed/NCBI
12	Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH, Lee Y, Choe IS and Kim JW: Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast. 13:383–388. 2004. View Article : Google Scholar : PubMed/NCBI
13	Wang H, Pan K, Zhang HK, Weng DS, Zhou J, Li JJ, Huang W, Song HF, Chen MS and Xia JC: Increased polycomb-group oncogene Bmi-1 expression correlates with poor prognosis in hepatocellular carcinoma. J Cancer Res Clin Oncol. 134:535–541. 2008. View Article : Google Scholar : PubMed/NCBI
14	Zhang X, Wang CX, Zhu CB, Zhang J, Kan SF, Du LT, Li W, Wang LL and Wang S: Overexpression of Bmi-1 in uterine cervical cancer: Correlation with clinicopathology and prognosis. Int J Gynecol Cancer. 20:1597–1603. 2010.PubMed/NCBI
15	Honig A, Weidler C, Häusler S, Krockenberger M, Buchholz S, Köster F, Segerer SE, Dietl J and Engel JB: Overexpression of polycomb protein BMI-1 in human specimens of breast, ovarian, endometrial and cervical cancer. Anticancer Res. 30:1559–1564. 2010.PubMed/NCBI
16	Guo BH, Feng Y, Zhang R, Xu LH, Li MZ, Kung HF, Song LB and Zeng MS: Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer. Mol Cancer. 10:102011. View Article : Google Scholar : PubMed/NCBI
17	Yuan W, Yuan Y, Zhang T and Wu S: Role of Bmi-1 in regulation of ionizing irradiation-induced epithelial-mesenchymal transition and migration of breast cancer cells. PLoS One. 10:e01187992015. View Article : Google Scholar : PubMed/NCBI
18	Wang MC, Jiao M, Wu T, Jing L, Cui J, Guo H, Tian T, Ruan ZP, Wei YC, Jiang LL, et al: Polycomb complex protein BMI-1 promotes invasion and metastasis of pancreatic cancer stem cells by activating PI3K/AKT signaling, an ex vivo, in vitro, and in vivo study. Oncotarget. 7:9586–9599. 2016.PubMed/NCBI
19	Silva J, García V, García JM, Peña C, Domínguez G, Díaz R, Lorenzo Y, Hurtado A, Sánchez A and Bonilla F: Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients. Breast Cancer Res. 9:R552007. View Article : Google Scholar : PubMed/NCBI
20	Abe S, Yamashita SI, Miyahara SO, Wakahara J, Yamamoto L, Mori R, Imamura N, Yoshida Y, Waseda R, Hiratsuka M, et al: Prognostic significance of BMI-1 But Not MEL-18 expression in pulmonary squamous cell carcinoma. Anticancer Res. 37:1923–1929. 2017. View Article : Google Scholar : PubMed/NCBI
21	Zhang X, Tian T, Sun W, Liu C and Fang X: Bmi-1 overexpression as an efficient prognostic marker in patients with nonsmall cell lung cancer. Medicine (Baltimore). 96:e73462017. View Article : Google Scholar : PubMed/NCBI
22	Engelsen IB, Mannelqvist M, Stefansson IM, Carter SL, Beroukhim R, Øyan AM, Otte AP, Kalland KH, Akslen LA and Salvesen HB: Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma. Br J Cancer. 98:1662–1669. 2008. View Article : Google Scholar : PubMed/NCBI
23	Li F, Liang A, Lv Y, Liu G, Jiang A and Liu P: MicroRNA-200c inhibits epithelial-mesenchymal transition by targeting the BMI-1 gene through the Phospho-AKT pathway in endometrial carcinoma cells in vitro. Med Sci Monit. 23:5139–5149. 2017. View Article : Google Scholar : PubMed/NCBI
24	FIGO Committee on Gynecologic Oncology, . FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 125:97–98. 2014. View Article : Google Scholar : PubMed/NCBI
25	Hellmann F, Verdi M, Schlemper BR Jr and Caponi S: 50th anniversary of the Declaration of Helsinki: The double standard was introduced. Arch Med Res. 45:600–601. 2014. View Article : Google Scholar : PubMed/NCBI
26	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
27	Makker A and Goel MM: Tumor progression, metastasis, and modulators of epithelial-mesenchymal transition in endometrioid endometrial carcinoma: An update. Endocr Relat Cancer. 23:R85–R111. 2016. View Article : Google Scholar : PubMed/NCBI
28	Mahdi H, Jernigan A, Nutter B, Michener C and Rose PG: Lymph node metastasis and pattern of recurrence in clinically early stage endometrial cancer with positive lymphovascular space invasion. J Gynecol Oncol. 26:208–213. 2015. View Article : Google Scholar : PubMed/NCBI
29	Devis L, Moiola CP, Masia N, Martinez-Garcia E, Santacana M, Stirbat TV, Brochard-Wyart F, García Á, Alameda F, Cabrera S, et al: Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early-stage endometrioid endometrial cancer. J Pathol. 241:475–487. 2017. View Article : Google Scholar : PubMed/NCBI
30	Giannella L, Cerami LB, Setti T, Bergamini E and Boselli F: Prediction of endometrial hyperplasia and cancer among premenopausal Women with abnormal uterine bleeding. Biomed Res Int. 2019:85981522019. View Article : Google Scholar : PubMed/NCBI
31	Khafaga A and Goldstein SR: Abnormal uterine bleeding. Obstet Gynecol Clin North Am. 46:595–605. 2019. View Article : Google Scholar : PubMed/NCBI
32	Goldstein SR and Lumsden MA: Abnormal uterine bleeding in perimenopause. Climacteric. 20:414–420. 2017. View Article : Google Scholar : PubMed/NCBI
33	Munro MG, Critchley HOD and Fraser IS; FIGO Menstrual Disorders Committee, : The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 143:393–408. 2018. View Article : Google Scholar : PubMed/NCBI
34	Stovall TG, Photopulos GJ, Poston WM, Ling FW and Sandlers LG: Pipelle endometrial sampling in patients with known endometrial carcinoma. Obstet Gynecol. 77:954–959. 1991.PubMed/NCBI
35	Guido RS, Kanbour-Shakir A, Rulin MC and Christopherson WA: Pipelle endometrial sampling. Sensitivity in the detection of endometrial cancer. J Reprod Med. 40:553–555. 1995.PubMed/NCBI
36	Peng HX, Liu XD, Luo ZY, Zhang XH, Luo XQ, Chen X, Jiang H and Xu L: Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia. BMC Cancer. 17:762017. View Article : Google Scholar : PubMed/NCBI
37	Song W, Tao K, Li H, Jin C, Song Z, Li J, Shi H, Li X, Dang Z and Dou K: Bmi-1 is related to proliferation, survival and poor prognosis in pancreatic cancer. Cancer Sci. 101:1754–1760. 2010. View Article : Google Scholar : PubMed/NCBI
38	Wang Y, Zhe H, Ding Z, Gao P, Zhang N and Li G: Cancer stem cell marker Bmi-1 expression is associated with basal-like phenotype and poor survival in breast cancer. World J Surg. 36:1189–1194. 2012. View Article : Google Scholar : PubMed/NCBI
39	Lei X, Li YF, Chen GD, Ou DP, Qiu XX, Zuo CH and Yang LY: Ack1 overexpression promotes metastasis and indicates poor prognosis of hepatocellular carcinoma. Oncotarget. 6:40622–40641. 2015. View Article : Google Scholar : PubMed/NCBI
40	Yang M, Xie X and Ding Y: SALL4 is a marker of poor prognosis in serous ovarian carcinoma promoting invasion and metastasis. Oncol Rep. 35:1796–1806. 2016. View Article : Google Scholar : PubMed/NCBI
41	Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI
42	Acloque H, Adams MS, Fishwick K, Bronner-Fraser M and Nieto MA: Epithelial-mesenchymal transitions: The importance of changing cell state in development and disease. J Clin Invest. 119:1438–1449. 2009. View Article : Google Scholar : PubMed/NCBI
43	Zeisberg M and Neilson EG: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 119:1429–1437. 2009. View Article : Google Scholar : PubMed/NCBI
44	Kalluri R and Weinberg RA: The basics of epithelial--mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
45	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
46	Tam WL and Weinberg RA: The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 19:1438–1449. 2013. View Article : Google Scholar : PubMed/NCBI
47	Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, Kong QL, Xu LH, Zhang X, Liu WL, et al: The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest. 119:3626–3636. 2009. View Article : Google Scholar : PubMed/NCBI
48	Li H, Song F, Chen X, Li Y, Fan J and Wu X: Bmi-1 regulates epithelial-to-mesenchymal transition to promote migration and invasion of breast cancer cells. Int J Clin Exp Pathol. 7:3057–3064. 2014.PubMed/NCBI
49	Yi C, Li BB and Zhou CX: Bmi-1 expression predicts prognosis in salivary adenoid cystic carcinoma and correlates with epithelial-mesenchymal transition-related factors. Ann Diagn Pathol. 22:38–44. 2016. View Article : Google Scholar : PubMed/NCBI
50	Liu Y, Chu Z, Li Q, Peng B, Xu S, Lian CG and Geng S: Downregulation of Bmi-1 suppresses epithelial-mesenchymal transition in melanoma. Oncol Rep. 37:139–146. 2017. View Article : Google Scholar : PubMed/NCBI
51	Zheng Z, Bao F, Chen X, Huang H and Zhang X: MicroRNA-330-3p expression indicates good prognosis and suppresses cell proliferation by targeting Bmi-1 in osteosarcoma. Cell Physiol Biochem. 46:442–450. 2018. View Article : Google Scholar : PubMed/NCBI
52	Joensuu K, Hagstrom J, Leidenius M, Haglund C, Andersson LC, Sariola H and Heikkilä P: Bmi-1, c-myc and Snail expression in primary breast cancers and their metastases-elevated Bmi-1 expression in late breast cancer relapses. Virchows Arch. 459:31–39. 2011. View Article : Google Scholar : PubMed/NCBI