Skip to main content
Erschienen in: Virchows Archiv 5/2021

31.07.2021 | Original Article

MicroRNA-21 expression in cancer cells is an independent biomarker of progression-free survival of endometrioid endometrial carcinoma

verfasst von: Kimiya Sato, Morikazu Miyamoto, Masashi Takano, Hitoshi Tsuda

Erschienen in: Virchows Archiv | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

Abstract

Endometrial carcinoma is one of the most common gynecological cancers. MicroRNA-21 (miR-21) is the most consistently overexpressed miRNA in almost all human cancer types, and it might be a useful clinical biomarker and therapeutic target. However, its precise localization and significance in endometrial carcinoma have not been clarified. This study aimed to examine miR-21 expression in endometrial carcinoma and reveal its clinicopathological importance. We investigated miR-21 expression by in situ hybridization (ISH) using locked nucleic acid (LNA)-modified probes in 230 endometrial carcinoma patients. We evaluated miR-21 expression in cancer cells and stroma separately. High miR-21 expression in cancer cells was significantly associated with higher histological grade and lymph node metastasis. In Kaplan–Meier analysis, high miR-21 expression in cancer cells was significantly associated with poor progression-free survival. In particular, in endometrioid carcinoma, high miR-21 expression in cancer cells was an independent prognostic factor associated with poor progression-free survival, as well as older age and higher International Federation of Gynecology and Obstetrics (FIGO) stage.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRef Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90CrossRef
2.
Zurück zum Zitat WHO Classification of Tumours Editorial Board (2020) Female Genital Tumours (WHO Classification of Tumours). IARC Press, Lyon WHO Classification of Tumours Editorial Board (2020) Female Genital Tumours (WHO Classification of Tumours). IARC Press, Lyon
3.
Zurück zum Zitat Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15:10–17CrossRef Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15:10–17CrossRef
4.
Zurück zum Zitat Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714CrossRef Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714CrossRef
5.
Zurück zum Zitat Bautista-Sánchez D, Arriaga-Canon C, Pedroza-Torres A et al (2020) The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics. Mol Ther Nucleic Acids 20:409–420CrossRef Bautista-Sánchez D, Arriaga-Canon C, Pedroza-Torres A et al (2020) The promising role of miR-21 as a cancer biomarker and its importance in RNA-based therapeutics. Mol Ther Nucleic Acids 20:409–420CrossRef
6.
Zurück zum Zitat Hermansen SK, Dahlrot RH, Nielsen BS, Hansen S, Kristensen BW (2013) MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J Neurooncol 111:71–81CrossRef Hermansen SK, Dahlrot RH, Nielsen BS, Hansen S, Kristensen BW (2013) MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J Neurooncol 111:71–81CrossRef
7.
Zurück zum Zitat Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M (2008) MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg 12:2171–2176CrossRef Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M (2008) MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg 12:2171–2176CrossRef
8.
Zurück zum Zitat Yamamichi N, Shimomura R, Inada K et al (2009) Locked nucleic acid in situ hybridization analysis of miR-21 expression during colorectal cancer development. Clin Cancer Res 15:4009–4016CrossRef Yamamichi N, Shimomura R, Inada K et al (2009) Locked nucleic acid in situ hybridization analysis of miR-21 expression during colorectal cancer development. Clin Cancer Res 15:4009–4016CrossRef
9.
Zurück zum Zitat Rask L, Balslev E, Jorgensen S et al (2011) High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer. APMIS 119:663–673CrossRef Rask L, Balslev E, Jorgensen S et al (2011) High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer. APMIS 119:663–673CrossRef
10.
Zurück zum Zitat Wang Y, Li J, Tong L et al (2013) The prognostic value of miR-21 and miR-155 in non-small-cell lung cancer: a meta-analysis. Jpn J Clin Oncol 43:813–820CrossRef Wang Y, Li J, Tong L et al (2013) The prognostic value of miR-21 and miR-155 in non-small-cell lung cancer: a meta-analysis. Jpn J Clin Oncol 43:813–820CrossRef
11.
Zurück zum Zitat Wang Y, Zhou S, Fan K, Jiang C (2019) MicroRNA-21 and its impact on signaling pathways in cervical cancer. Oncol Lett 17:3066–3070PubMedPubMedCentral Wang Y, Zhou S, Fan K, Jiang C (2019) MicroRNA-21 and its impact on signaling pathways in cervical cancer. Oncol Lett 17:3066–3070PubMedPubMedCentral
12.
Zurück zum Zitat Qin X, Yan L, Zhao X, Li C, Fu Y (2012) microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer. Oncol Lett 4:1290–1296CrossRef Qin X, Yan L, Zhao X, Li C, Fu Y (2012) microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer. Oncol Lett 4:1290–1296CrossRef
13.
Zurück zum Zitat Zhao W, Geng P, Li Y, Wei X, Cheng J (2017) MicroRNA-21 promotes endometrial carcinoma proliferation and invasion by targeting PTEN. Int J Clin Exp Pathol 10:11489–11495PubMedPubMedCentral Zhao W, Geng P, Li Y, Wei X, Cheng J (2017) MicroRNA-21 promotes endometrial carcinoma proliferation and invasion by targeting PTEN. Int J Clin Exp Pathol 10:11489–11495PubMedPubMedCentral
14.
Zurück zum Zitat Gao Y, Dai M, Liu H et al (2016) Diagnostic value of circulating miR-21: an update meta-analysis in various cancers and validation in endometrial cancer. Oncotarget 7:68894–68908CrossRef Gao Y, Dai M, Liu H et al (2016) Diagnostic value of circulating miR-21: an update meta-analysis in various cancers and validation in endometrial cancer. Oncotarget 7:68894–68908CrossRef
15.
Zurück zum Zitat Wang C, Li Q, He Y (2020) MicroRNA-21-5p promotes epithelial to mesenchymal transition by targeting SRY-box 17 in endometrial cancer. Oncol Rep 43:1897–1905PubMedPubMedCentral Wang C, Li Q, He Y (2020) MicroRNA-21-5p promotes epithelial to mesenchymal transition by targeting SRY-box 17 in endometrial cancer. Oncol Rep 43:1897–1905PubMedPubMedCentral
16.
Zurück zum Zitat Eriksen AH, Andersen RF, Nielsen BS et al (2016) Intratumoral heterogeneity of microRNA expression in rectal cancer. PLoS One 11:e0156919CrossRef Eriksen AH, Andersen RF, Nielsen BS et al (2016) Intratumoral heterogeneity of microRNA expression in rectal cancer. PLoS One 11:e0156919CrossRef
17.
Zurück zum Zitat Zedan AH, Blavnsfeldt SG, Hansen TF et al (2017) Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations. PLoS One 12:e0179113CrossRef Zedan AH, Blavnsfeldt SG, Hansen TF et al (2017) Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations. PLoS One 12:e0179113CrossRef
18.
Zurück zum Zitat Chen C, Ridzon DA, Broomer AJ et al (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179CrossRef Chen C, Ridzon DA, Broomer AJ et al (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179CrossRef
19.
Zurück zum Zitat Cao Z, Yoon JH, Nam SW, Lee JY, Park WS (2012) PDCD4 expression inversely correlated with miR-21 levels in gastric cancers. J Cancer Res Clin Oncol 138:611–619CrossRef Cao Z, Yoon JH, Nam SW, Lee JY, Park WS (2012) PDCD4 expression inversely correlated with miR-21 levels in gastric cancers. J Cancer Res Clin Oncol 138:611–619CrossRef
20.
Zurück zum Zitat Peltier HJ, Latham GJ (2008) Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 14:844–852CrossRef Peltier HJ, Latham GJ (2008) Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA 14:844–852CrossRef
21.
Zurück zum Zitat Viera AJ, Garrett JM (2005) Understanding interobserver agreement: the kappa statistic. Fam Med 37:360–363PubMed Viera AJ, Garrett JM (2005) Understanding interobserver agreement: the kappa statistic. Fam Med 37:360–363PubMed
22.
Zurück zum Zitat McHugh ML (2012) Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22:276–282CrossRef McHugh ML (2012) Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22:276–282CrossRef
23.
Zurück zum Zitat Kadera BE, Li L, Toste PA et al (2013) MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One 8:e71978CrossRef Kadera BE, Li L, Toste PA et al (2013) MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One 8:e71978CrossRef
24.
Zurück zum Zitat Uozaki H, Morita S, Kumagai A et al (2014) Stromal miR-21 is more important than miR-21 of tumour cells for the progression of gastric cancer. Histopathology 65:775–783CrossRef Uozaki H, Morita S, Kumagai A et al (2014) Stromal miR-21 is more important than miR-21 of tumour cells for the progression of gastric cancer. Histopathology 65:775–783CrossRef
Metadaten
Titel
MicroRNA-21 expression in cancer cells is an independent biomarker of progression-free survival of endometrioid endometrial carcinoma
verfasst von
Kimiya Sato
Morikazu Miyamoto
Masashi Takano
Hitoshi Tsuda
Publikationsdatum
31.07.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 5/2021
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-021-03171-w

Weitere Artikel der Ausgabe 5/2021

Virchows Archiv 5/2021 Zur Ausgabe

Neu im Fachgebiet Pathologie

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Molekularpathologische Untersuchungen im Wandel der Zeit

11.04.2024 | Pathologie | Schwerpunkt: Next Generation Pathology

Vergleichende Pathologie in der onkologischen Forschung

Open Access 08.04.2024 | GIST | CME

Gastrointestinale Stromatumoren

Wo stehen wir?

03.04.2024 | Zielgerichtete Therapie | Schwerpunkt: Next Generation Pathology

Personalisierte Medizin in der Onkologie