Analysis of microRNA Expression in Liquid-Based Cytology Samples May Be Useful for Primary Lung Cancer Diagnosis.

OBJECTIVES Bronchoscopy is frequently performed for patients suspected of having lung cancer; however, we sometimes fail to make a definitive diagnosis, resulting in additional invasive testing. Many studies indicate that microRNAs (miRs) are abnormally expressed in cancers. We examined the diagnostic value of 4 miRs (miR-21, miR-31, miR-182, and miR-183) extracted from liquid-based cytology (LBC) samples and validated whether they were diagnostically useful. METHODS We collected 18 surgically resected tissue samples and 136 LBC specimens obtained during bronchoscopic examination at Hiroshima University Hospital. We extracted RNA from these samples and compared the expression of 4 miRs by reverse transcription-quantitative polymerase chain reaction. RESULTS We confirmed that expression of the 4 miRs was significantly higher in cancer tissues than in tumor-adjacent normal tissues. We examined the expression of these miRs in 125 (cancer cases, 83; noncancer cases, 42) of 136 cytologic samples. Expression of all 4 miRs was significantly higher in patients with lung cancer than in those without lung cancer. Among samples judged as benign or indeterminate, levels of these miRs were also significantly higher in patients with lung cancer than in those without lung cancer. CONCLUSIONS The analysis of miR expression in LBC samples might be helpful for primary lung cancer diagnosis.

[1]  Baosen Zhou,et al.  Clinically Correlated MicroRNAs in the Diagnosis of Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis , 2018, BioMed research international.

[2]  Joshua D. Campbell,et al.  Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection , 2017, Cancer Prevention Research.

[3]  Hui Xia,et al.  miR-21 modulates the effect of EZH2 on the biological behavior of human lung cancer stem cells in vitro , 2017, Oncotarget.

[4]  D. Xie,et al.  Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non–Small Cell Lung Cancer Using Next-Generation Sequencing , 2017, Clinical Cancer Research.

[5]  H. Ji,et al.  The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis , 2017, Oncogene.

[6]  K. Shimada,et al.  Evaluation of RNA and DNA extraction from liquid‐based cytology specimens , 2016, Diagnostic cytopathology.

[7]  C. Xiao,et al.  The MicroRNA-183-96-182 Cluster Promotes T Helper 17 Cell Pathogenicity by Negatively Regulating Transcription Factor Foxo1 Expression. , 2016, Immunity.

[8]  X. Liu,et al.  Diagnostic Value of Serum miR-182, miR-183, miR-210, and miR-126 Levels in Patients with Early-Stage Non-Small Cell Lung Cancer , 2016, PloS one.

[9]  Zhongming Zhao,et al.  MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. , 2015, The Journal of clinical investigation.

[10]  Klaus Pantel,et al.  Data Normalization Strategies for MicroRNA Quantification. , 2015, Clinical chemistry.

[11]  Zhen Liu,et al.  miR-31 functions as an oncogene in cervical cancer , 2015, Archives of Gynecology and Obstetrics.

[12]  Hao Wang,et al.  MiR-21 promotes intrahepatic cholangiocarcinoma proliferation and growth in vitro and in vivo by targeting PTPN14 and PTEN , 2015, Oncotarget.

[13]  Hui Zhang,et al.  MiR-183/-96/-182 cluster is up-regulated in most breast cancers and increases cell proliferation and migration , 2014, Breast Cancer Research.

[14]  C. Shaw,et al.  MicroRNA Expression Differences in Human Hematopoietic Cell Lineages Enable Regulated Transgene Expression , 2014, PloS one.

[15]  G. Yousef,et al.  Clinical evaluation of microRNA expression profiling in non small cell lung cancer. , 2013, Lung cancer.

[16]  R. Kolde,et al.  Meta‐analysis of microRNA expression in lung cancer , 2013, International journal of cancer.

[17]  Lei Yang,et al.  The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. , 2013, International journal of oncology.

[18]  Yingyong Hou,et al.  Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens. , 2012, American journal of respiratory and critical care medicine.

[19]  Xiao-guang Liu,et al.  High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer , 2012, Medical Oncology.

[20]  J. Steen,et al.  Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma , 2012, Acta Neuropathologica.

[21]  W. De,et al.  Prognostic significance of serum miRNA‐21 expression in human non‐small cell lung cancer , 2011, Journal of surgical oncology.

[22]  X. Liu,et al.  Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: A case control study , 2011, BMC Cancer.

[23]  Nicola J. Armstrong,et al.  Haemolysis during Sample Preparation Alters microRNA Content of Plasma , 2011, PloS one.

[24]  Subbaya Subramanian,et al.  MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. , 2010, Cancer research.

[25]  E. Olson,et al.  Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. , 2010, Cancer cell.

[26]  Guanghai Yang,et al.  MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). , 2010, Clinica chimica acta; international journal of clinical chemistry.

[27]  Fei Li,et al.  Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. , 2010, Biochemical and biophysical research communications.

[28]  E. Dmitrovsky,et al.  MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. , 2010, The Journal of clinical investigation.

[29]  Hong Peng,et al.  Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. , 2010, Lung cancer.

[30]  Shu Zheng,et al.  MicroRNA‐183 regulates Ezrin expression in lung cancer cells , 2008, FEBS letters.

[31]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[32]  Chin-Wen Chi,et al.  miR-21 microRNA expression in human gastric carcinomas and its clinical association. , 2008, Anticancer research.

[33]  Shuomin Zhu,et al.  miR-21-mediated tumor growth , 2007, Oncogene.

[34]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[35]  R. Liu,et al.  miR-21 modulates prostaglandin signaling and promotes gastric tumorigenesis by targeting 15-PGDH. , 2018, Biochemical and biophysical research communications.