Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer.

BACKGROUND MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

[1]  Qiong Wu,et al.  Recent advances of miRNAs in the development and clinical application of gastric cancer , 2020, Chinese medical journal.

[2]  L. G. de Almeida Chuffa,et al.  The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers. , 2020, Life sciences.

[3]  S. Mayer,et al.  Discovery of potential serum and urine-based microRNA as minimally-invasive biomarkers for breast and gynecological cancer. , 2020, Cancer biomarkers : section A of Disease markers.

[4]  Jun-ling Wang,et al.  Identification of microRNAs as novel biomarkers for esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas (TCGA) and bioinformatics , 2019, Chinese medical journal.

[5]  R. Cui,et al.  Circulating MicroRNAs in Cancer: Potential and Challenge , 2019, Front. Genet..

[6]  Mu Xu,et al.  A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma. , 2018, Current problems in cancer.

[7]  Jie Shen,et al.  Long non-coding RNA NIFK-AS1 inhibits M2 polarization of macrophages in endometrial cancer through targeting miR-146a. , 2018, The international journal of biochemistry & cell biology.

[8]  X. Zhang,et al.  Dual functional roles of the MyD88 signaling in colorectal cancer development. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[9]  Suping Han,et al.  miR-146a promotes cervical cancer cell viability via targeting IRAK1 and TRAF6. , 2018, Oncology reports.

[10]  L. Xue,et al.  Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage , 2018, Clinical Epigenetics.

[11]  C. C. Grigorescu,et al.  Clinical and morphological correlations in early diagnosis of endometrial cancer. , 2018, Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie.

[12]  D. G. Zisoulis,et al.  miR-151a induces partial EMT by regulating E-cadherin in NSCLC cells , 2017, Oncogenesis.

[13]  G. Lippi,et al.  Aberrant MicroRNA Expression in Patients With Endometrial Cancer , 2016, International Journal of Gynecologic Cancer.

[14]  Lingyun Zhang,et al.  Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1 , 2016, International Journal of Gynecologic Cancer.

[15]  Donghong Zhang,et al.  Serum miRNAs panel (miR-16-2*, miR-195, miR-2861, miR-497) as novel non-invasive biomarkers for detection of cervical cancer , 2015, Scientific Reports.

[16]  Y. Miao,et al.  MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7 , 2015, Tumor Biology.

[17]  Artemis G. Hatzigeorgiou,et al.  DIANA-miRPath v3.0: deciphering microRNA function with experimental support , 2015, Nucleic Acids Res..

[18]  A. Hölscher,et al.  Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor , 2015, Tumor Biology.

[19]  Yanmei Xu,et al.  Exosomes: Novel Biomarkers for Clinical Diagnosis , 2015, TheScientificWorldJournal.

[20]  Y. Shu,et al.  MiR-4728-3p could act as a marker of HER2 status. , 2015, Cancer biomarkers : section A of Disease markers.

[21]  X. Shen,et al.  Circulating microRNAs as a Fingerprint for Endometrial Endometrioid Adenocarcinoma , 2014, PloS one.

[22]  Zebo Huang,et al.  Prognostic Value of miR-21 in Various Cancers: An Updating Meta-Analysis , 2014, PloS one.

[23]  Zuhong Lu,et al.  miRNA in Plasma Exosome is Stable under Different Storage Conditions , 2014, Molecules.

[24]  Chenyu Zhang,et al.  Identification of four serum microRNAs from a genome-wide serum microRNA expression profile as potential non-invasive biomarkers for endometrioid endometrial cancer , 2013, Oncology letters.

[25]  G. Zamboni,et al.  Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients , 2013, International journal of cancer.

[26]  T. Ørntoft,et al.  Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs , 2011, BMC Genomics.

[27]  Alicia Algeciras-Schimnich,et al.  Analysis of circulating microRNA: preanalytical and analytical challenges. , 2011, Clinical chemistry.

[28]  Muneesh Tewari,et al.  Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). , 2010, Methods.

[29]  Anindya Dutta,et al.  MicroRNAs in cancer. , 2009, Annual review of pathology.

[30]  Cicek Gercel-Taylor,et al.  MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. , 2008, Gynecologic oncology.

[31]  B. Degnan,et al.  Real-time RT-PCR quantification of Kuruma shrimp transcripts: a comparison of relative and absolute quantification procedures. , 2007, Journal of biotechnology.

[32]  E. Asselin,et al.  Regulation of COX-2 protein expression by Akt in endometrial cancer cells is mediated through NF-κB/IκB pathway , 2004, Molecular Cancer.

[33]  T. Vaskivuo,et al.  Apoptosis and apoptosis‐related factors Bcl‐2, Bax, tumor necrosis factor‐α, and NF‐κB in human endometrial hyperplasia and carcinoma , 2002 .

[34]  R. Erkkola,et al.  The expression of cyclooxygenase-1 and -2 in proliferative endometrium and endometrial adenocarcinoma , 2002, Annals of medicine.

[35]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[36]  H. Critchley,et al.  The NF-κB pathway in human endometrium and first trimester decidua , 2001 .

[37]  D. Baird,et al.  Prostaglandins and menstruation. , 1996, European journal of obstetrics, gynecology, and reproductive biology.

[38]  R. Kelly Pregnancy maintenance and parturition: the role of prostaglandin in manipulating the immune and inflammatory response. , 1994, Endocrine reviews.