MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes

Details

• Personal Author:
  Cao S ; Guo NL ; Luo D ; Qian Y ; Raese R ; Wan Y-W ; Ye Q
• Description:
  The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes. [Description provided by NIOSH]
• Subjects:
  Biomarkers Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Lung Cancer CRISPR-Cas9/RNAi Diagnosis Drug Response Genes Lung Cancer Metastatic Disease Prognosis Proteins Radiotherapy Response Repositioning Drugs Treatment Tumors

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• ISSN:
  2072-6694
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  15
• Issue:
  8
• NIOSHTIC Number:
  nn:20067549
• Citation:
  Cancers 2023 Apr; 15(8):2294
• Contact Point Address:
  Nancy Lan Guo, Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, WV 26506
• Email:
  lguo@hsc.wvu.edu
• Federal Fiscal Year:
  2023
• Peer Reviewed:
  True
• Source Full Name:
  Cancers
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:be8b5a5185a7d77943ed07183fbfe6f94c385a04ad9f146e072dbc7af7e7419d1de3d929c572c110a20ce8e6b6e931d377e5b01991be8159e6f13d72392e1d26
• Download URL:
  https://stacks.cdc.gov/view/cdc/231492/cdc_231492_DS1.pdf
• File Type:
  [PDF - 3.76 MB ]