Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

A Five-microRNA Signature as Risk Stratification System in Uterine Corpus Endometrial Carcinoma

Author(s): Zhichao Chen, Xiaoyuan Huang*, Yufeng Lv*, Yuan Fang, Lili Pan, Zuhuan Gan, Zhong Huang and Wenhao Wei

Volume 24, Issue 2, 2021

Published on: 30 July, 2020

Page: [187 - 194] Pages: 8

DOI: 10.2174/1386207323999200730211227

Price: $65

Abstract

Background: MicroRNAs (miRs) have been shown to play important roles in various cancers and may be a reliable prognostic marker. However, its prognostic value in endometrial carcinoma (UCEC) needs to be further explored.

Objectives: The aim of this study was to create a miR-based signature to effectively predict the prognosis for patients with uterine corpus endometrial carcinoma (UCEC).

Methods: Using UCEC data set in TCGA, we identified differentially expressed miRs between UCEC and healthy endometrial tissues. The LASSO method was used to construct a miR-based signature prognosis index for predicting prognosis in the training cohort. The miR-based signature prognosis index was validated in an independent test cohort. MiRNet tool was applied to perform functional enrichment analysis of this miR-based signature.

Results: A total of 208 miRs were differentially expressed between UCEC and healthy endometrial tissues. Five miRs (miR-652, miR-3170, miR-195, miR-34a, and miR-934) were identified to generate a prognosis index (PI). The five-miR signature is a promising biomarker for predicting the 5-year-survival rate of UCEC with AUC = 0.730. The PI remained an independent prognostic factor adjusted by routine clinicopathologic factors. Using the PI, we could successfully identify the high-risk individuals, furthermore, it still worked in an independent test cohort. The five miRs involved in various pathways associated with cancer.

Conclusion: We proposed and validated a five-miR signature that could serve as an independent prognostic predictor of UCECs.

Keywords: Uterine corpus endometrial carcinoma, gynaecology tumor, microRNA signature, prognosis, risk stratification system, TCGA.

[1]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[2]
Evans-Metcalf, E.R.; Brooks, S.E.; Reale, F.R.; Baker, S.P. Profile of women 45 years of age and younger with endometrial cancer. Obstet. Gynecol., 1998, 91(3), 349-354.
[http://dx.doi.org/10.1016/S0029-7844(97)00668-6] [PMID: 9491858]
[3]
Lee, T.S.; Jung, J.Y.; Kim, J.W.; Park, N.H.; Song, Y.S.; Kang, S.B.; Lee, H.P. Feasibility of ovarian preservation in patients with early stage endometrial carcinoma. Gynecol. Oncol., 2007, 104(1), 52-57.
[http://dx.doi.org/10.1016/j.ygyno.2006.07.003] [PMID: 16887175]
[4]
Practice Bulletin No. Practice Bulletin No. 149: Endometrial cancer. Obstet. Gynecol., 2015, 125(4), 1006-1026.
[http://dx.doi.org/10.1097/01.AOG.0000462977.61229.de] [PMID: 25798986]
[5]
Bokhman, J.V. Two pathogenetic types of endometrial carcinoma. Gynecol. Oncol., 1983, 15(1), 10-17.
[http://dx.doi.org/10.1016/0090-8258(83)90111-7] [PMID: 6822361]
[6]
McAlpine, J.N.; Temkin, S.M.; Mackay, H.J. Endometrial cancer: Not your grandmother’s cancer. Cancer, 2016, 122(18), 2787-2798.
[http://dx.doi.org/10.1002/cncr.30094] [PMID: 27308732]
[7]
Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[8]
Wiemer, E.A. The role of microRNAs in cancer: no small matter. Eur. J. Cancer, 2007, 43(10), 1529-1544.
[http://dx.doi.org/10.1016/j.ejca.2007.04.002] [PMID: 17531469]
[9]
Hou, L.J.; Zhai, J.J. Aberrant expression profile of translationally controlled tumor protein and tumor-suppressive microRNAs in cervical cancer. J. BUON, 2015, 20(6), 1504-1509.
[PMID: 26854447]
[10]
Ghanbari, R.; Rezasoltani, S.; Hashemi, J.; Mohamadkhani, A.; Tahmasebifar, A.; Arefian, E.; Mobarra, N.; Asadi, J.; Nazemalhosseini Mojarad, E.; Yazdani, Y.; Knuutila, S.; Malekzadeh, R. Expression analysis of previously verified fecal and plasma dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE tissue samples of CRC patients. Arch. Iran Med., 2017, 20(2), 92-95.
[PMID: 28193082]
[11]
Lin, Y.; Lv, Y.; Liang, R.; Yuan, C.; Zhang, J.; He, D.; Zheng, X.; Zhang, J. Four-miRNA signature as a prognostic tool for lung adenocarcinoma. OncoTargets Ther., 2017, 11, 29-36.
[http://dx.doi.org/10.2147/OTT.S155016] [PMID: 29317831]
[12]
Schultz, N.A.; Andersen, K.K.; Roslind, A.; Willenbrock, H.; Wøjdemann, M.; Johansen, J.S. Prognostic microRNAs in cancer tissue from patients operated for pancreatic cancer--five microRNAs in a prognostic index. World J. Surg., 2012, 36(11), 2699-2707.
[http://dx.doi.org/10.1007/s00268-012-1705-y] [PMID: 22851141]
[13]
Yu, L.; Xiang, L.; Feng, J.; Li, B.; Zhou, Z.; Li, J.; Lin, Y.; Lv, Y.; Zou, D.; Lei, Z.; Zhang, J. miRNA-21 and miRNA-223 expression signature as a predictor for lymph node metastasis, distant metastasis and survival in kidney renal clear cell carcinoma. J. Cancer, 2018, 9(20), 3651-3659.
[http://dx.doi.org/10.7150/jca.27117] [PMID: 30405833]
[14]
Hess, J.; Unger, K.; Maihoefer, C.; Schuttrumpf, L.; Wintergerst, L.; Heider, T.; Weber, P.; Marschner, S.; Braselmann, H.; Samaga, D.; Kuger, S.; Pflugradt, U.; Baumeister, P. A Five-MicroRNA signature predicts survival and disease control of patients with head and neck cancer negative for HPV-infection. Clin. Cancer Res., 2018.
[PMID: 30171046]
[15]
Kandimalla, R.; Gao, F.; Matsuyama, T.; Ishikawa, T.; Uetake, H.; Takahashi, N.; Yamada, Y.; Becerra, C.; Kopetz, S.; Wang, X.; Goel, A. Genome-wide discovery and identification of a novel miRNA signature for recurrence prediction in stage ii and iii colorectal cancer. Clin. Cancer Res., 2018, 24(16), 3867-3877.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3236] [PMID: 29514841]
[16]
Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 2015, 43(7)e47
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[17]
Gan, Z.; Zou, Q.; Lin, Y.; Huang, X.; Huang, Z.; Chen, Z.; Xu, Z.; Lv, Y. Construction and validation of a seven-microRNA signature as a prognostic tool for lung squamous cell carcinoma. Cancer Manag. Res., 2019, 11, 5701-5709.
[http://dx.doi.org/10.2147/CMAR.S191637] [PMID: 31417313]
[18]
Tibshirani, R. The lasso method for variable selection in the Cox model. Stat. Med., 1997, 16(4), 385-395.
[http://dx.doi.org/10.1002/(SICI)1097-0258(19970228)16:4<385:AID-SIM380>3.0.CO;2-3] [PMID: 9044528]
[19]
Heagerty, P.J.; Lumley, T.; Pepe, M.S. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics, 2000, 56(2), 337-344.
[http://dx.doi.org/10.1111/j.0006-341X.2000.00337.x] [PMID: 10877287]
[20]
Fan, Y.; Siklenka, K.; Arora, S.K.; Ribeiro, P.; Kimmins, S.; Xia, J. miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis. Nucleic Acids Res., 2016, 44(W1)W135-41
[http://dx.doi.org/10.1093/nar/gkw288] [PMID: 27105848]
[21]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[22]
Kandoth, C.; Schultz, N.; Cherniack, A.D.; Akbani, R.; Liu, Y.; Shen, H.; Robertson, A.G.; Pashtan, I.; Shen, R.; Benz, C.C.; Yau, C.; Laird, P.W.; Ding, L.; Zhang, W.; Mills, G.B.; Kucherlapati, R.; Mardis, E.R.; Levine, D.A. Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature, 2013, 497(7447), 67-73.
[http://dx.doi.org/10.1038/nature12113] [PMID: 23636398]
[23]
Wang, Y.; Xu, M.; Yang, Q. A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma. Curr. Probl. Cancer, 2018.
[PMID: 29567372]
[24]
Jayaraman, M.; Radhakrishnan, R.; Mathews, C.A.; Yan, M.; Husain, S.; Moxley, K.M.; Song, Y.S.; Dhanasekaran, D.N. Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer. Genes Cancer, 2017, 8(5-6), 566-576.
[PMID: 28740575]
[25]
Karaayvaz, M.; Zhang, C.; Liang, S.; Shroyer, K.R.; Ju, J. Prognostic significance of miR-205 in endometrial cancer. PLoS One, 2012, 7(4)e35158
[http://dx.doi.org/10.1371/journal.pone.0035158] [PMID: 22514717]
[26]
Rupaimoole, R.; Slack, F.J. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov., 2017, 16(3), 203-222.
[http://dx.doi.org/10.1038/nrd.2016.246] [PMID: 28209991]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy