Prognostic Significance of microRNA-221/222 Expression in Cancers: Evidence from 1,204 Subjects

Background The prognostic significance of the expression of the miR-221/222 family in cancer remains controversial. We here performed a meta-analysis of published data investigating the effects of miR-221/222 expression on both overall survival (OS) and disease-free survival (DFS) among patients with cancer. Methods A systematic search of the PubMed, Embase, Cochrane, and CNKI databases was performed with the last search being updated on March 15, 2013. The hazard ratio (HR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Results A total of 17 studies involving 1,204 subjects were included in this meta-analysis. When assessing the prognostic significance of miR-221 expression, the pooled HR was 1.91 (95% CI: 1.28-2.85, p=0.002) for OS and 1.36 (95% CI: 0.88-2.09, p=0.163) for DFS. When assessing the prognostic significance of miR-222 expression, the pooled HR was 2.15 (95% CI: 1.51-3.06, p<0.0001) for OS and 1.37 (95% CI: 0.45-4.13, p=0.581) for DFS. We also found that an elevated miR-221 expression was significantly associated with poor OS when stratifying by ethnicity, cancer type, statistical methodology, sample, and quality assessment. There was no evidence of publication bias. Conclusion The meta-analysis demonstrates that the elevated expression of miR-221 and miR-222 is associated with poor OS in patients with cancer. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. More work is required to fully elucidate the role of the miR-221/222 family in human tumors.

[1]  Wei Zhang,et al.  Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis , 2013, Disease markers.

[2]  G. Sun,et al.  Protective Role of Helicobacter pylori Infection in Prognosis of Gastric Cancer: Evidence from 2454 Patients with Gastric Cancer , 2013, PloS one.

[3]  M. Gazouli,et al.  Expression of microRNAs, miR‐21, miR‐31, miR‐122, miR‐145, miR‐146a, miR‐200c, miR‐221, miR‐222, and miR‐223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance , 2013, Molecular carcinogenesis.

[4]  S. Choi,et al.  Prognostic implications for high expression of oncogenic microRNAs in advanced gastric carcinoma. , 2013 .

[5]  Jong Y. Park,et al.  miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases. , 2013, Asian journal of andrology.

[6]  S. Meltzer,et al.  MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. , 2012, Gastroenterology.

[7]  Lei Han,et al.  High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma , 2012, Journal of Translational Medicine.

[8]  Carlos Cordon-Cardo,et al.  miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer. , 2012, The American journal of pathology.

[9]  John P A Ioannidis,et al.  Clinical outcome prediction by microRNAs in human cancer: a systematic review. , 2012, Journal of the National Cancer Institute.

[10]  C. Fan,et al.  Increased Expression of MicroRNA-221 in Gastric Cancer and Its Clinical Significance , 2012, The Journal of international medical research.

[11]  E. Howe,et al.  The miR-200 and miR-221/222 microRNA Families: Opposing Effects on Epithelial Identity , 2012, Journal of Mammary Gland Biology and Neoplasia.

[12]  J. Michálek,et al.  MiR‐195, miR‐196b, miR‐181c, miR‐21 expression levels and O‐6‐methylguanine‐DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients , 2011, Cancer science.

[13]  A. Hui,et al.  Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies , 2011, BMC Cancer.

[14]  Xiaonan Fu,et al.  Prognostic role of microRNA‐21 in various carcinomas: a systematic review and meta‐analysis , 2011, European journal of clinical investigation.

[15]  E. Han,et al.  Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma. , 2011, Human pathology.

[16]  C. Croce,et al.  MicroRNA profiling for the identification of cancers with unknown primary tissue‐of‐origin , 2011, The Journal of pathology.

[17]  Wen Li,et al.  Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma , 2011, Molecular Biology Reports.

[18]  R. Tibshirani,et al.  MicroRNAs Are Independent Predictors of Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP , 2011, Clinical Cancer Research.

[19]  Wanjun Yu,et al.  Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. , 2011, Biochemical and biophysical research communications.

[20]  Maria Kafousi,et al.  MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer , 2011, Cell cycle.

[21]  Chengcheng Guo,et al.  Diagnostic and Prognostic Value of Circulating miR-221 for Extranodal Natural Killer/T-Cell Lymphoma , 2011, Disease markers.

[22]  R. Govindan,et al.  Use of MicroRNA Expression Levels to Predict Outcomes in Resected Stage I Non-small Cell Lung Cancer , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[23]  Tongyu Lin,et al.  Circulating miR‐221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression , 2010, Journal of gastroenterology and hepatology.

[24]  P. Pu,et al.  MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN , 2010, BMC Cancer.

[25]  Muneesh Tewari,et al.  MiR‐221 and MiR‐222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival , 2010, Genes, chromosomes & cancer.

[26]  Jianjun Chen,et al.  MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. , 2010, Blood cells, molecules & diseases.

[27]  K. Choy,et al.  MiR-222 Overexpression Confers Cell Migratory Advantages in Hepatocellular Carcinoma through Enhancing AKT Signaling , 2010, Clinical Cancer Research.

[28]  Hansjuerg Alder,et al.  miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. , 2009, Cancer cell.

[29]  Gian Luca Grazi,et al.  MicroRNA-221 Targets Bmf in Hepatocellular Carcinoma and Correlates with Tumor Multifocality , 2009, Clinical Cancer Research.

[30]  G. Kristiansen,et al.  Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma , 2009, International journal of cancer.

[31]  C. Scholz,et al.  Expression of microRNA‐221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence , 2009, International Journal of Cancer.

[32]  Lu Jiang,et al.  MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines. , 2009, Cancer genomics & proteomics.

[33]  Tyler E. Miller,et al.  MicroRNA-221/222 Confers Tamoxifen Resistance in Breast Cancer by Targeting p27Kip1*♦ , 2008, Journal of Biological Chemistry.

[34]  C. Croce,et al.  MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer , 2008, Oncogene.

[35]  Leonard D. Goldstein,et al.  MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype , 2007, Genome Biology.

[36]  C. Croce,et al.  MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. , 2007, Endocrine-related cancer.

[37]  Giovanni Vanni Frajese,et al.  miR-221 and miR-222 Expression Affects the Proliferation Potential of Human Prostate Carcinoma Cell Lines by Targeting p27Kip1* , 2007, Journal of Biological Chemistry.

[38]  C. Benz,et al.  Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies , 2006, Molecular Cancer.

[39]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  C. Croce,et al.  MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Matakidou,et al.  Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[43]  I. Olkin,et al.  Meta-analysis of observational studies in epidemiology - A proposal for reporting , 2000 .

[44]  M. Parmar,et al.  Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. , 1998, Statistics in medicine.

[45]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[46]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[47]  B. Woolf.  ON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE , 1955, Annals of human genetics.

[48]  Chen Haicha.  Expression of MicroRNA-21 in gastric cancer , 2013 .

[49]  G-D Zhuang.  Increased MiR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro , 2013 .

[50]  Hao Jun-we.  MiR-221 Expression Affects Invasion Potential of Human Prostate Carcinoma Cell Lines , 2012 .

[51]  C. Croce,et al.  miR221/222 in cancer: their role in tumor progression and response to therapy. , 2012, Current molecular medicine.

[52]  F. Wang,et al.  MicroRNAs as promising biomarkers for gastric cancer. , 2012, Cancer biomarkers : section A of Disease markers.

[53]  H. Taubert,et al.  Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival , 2010, International journal of cancer.