A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-Small Cell Lung Cancer

Details

• Personal Author:
  Beer DG ; Bokhary U ; Chen G ; Dong C ; Dowlati A ; Guo NL ; Hensing T ; Howington J ; Liu L ; Qian Y ; Raese RA ; Shaffer J ; Singh S
• Description:
  Purpose: This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets. Patients and methods: The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples. Results: A 7-gene signature was identified from training cohort (n = 83) with accurate patient stratification (P = 0.0043) and was validated in independent patient cohorts (n = 248, P < 0.0001) in Kaplan-Meier analyses. In the predicted benefit group, there was a significantly better disease-specific survival in patients receiving adjuvant chemotherapy in both training (P = 0.035) and validation (P = 0.0049) sets. In the predicted non-benefit group, there was no survival benefit in patients receiving chemotherapy in either set. The protein expression of ZNF71 quantified with AQUA scores produced robust patient stratification in separate training (P = 0.021) and validation (P = 0.047) NSCLC cohorts. The protein expression of CD27 quantified with ELISA had a strong correlation with its mRNA expression in NSCLC tumors (Spearman coefficient = 0.494, P < 0.0088). Multiple signature genes had concordant DNA copy number variation, mRNA and protein expression in NSCLC progression. Conclusions: This study presents a predictive multi-gene assay and prognostic protein biomarkers clinically applicable for improving NSCLC treatment, with important implications in lung cancer chemotherapy and immunotherapy. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers Decision Making Enzymes Genetics Immune System Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Analytical Models Author Keywords: Predictive Gene Assay Bioassays Cancer Survivors Cell Biology Cell Signaling Cellular Function Cellular Reactions Chemotherapy Clinical Techniques Decision Making DNA Microarrays ELISA Enzyme-linked Immunosorbent Assay Gene Expression Genes Immune System Immunoassays Immunotherapy Lung Cancer Lung Cells Lung Disease Medical Treatment Non-small Cell Lung Cancer NSCLC Precision Therapy Prognostic Protein Biomarkers Proteins Ribonucleic Acids RNA Statistical Quality Control Survival Rate Target Organs Therapeutic Agents Tumors

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• ISSN:
  2352-3964
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; Michigan ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  102-110
• Volume:
  32
• NIOSHTIC Number:
  nn:20051852
• Citation:
  EBioMedicine 2018 Jun; 32:102-110
• Contact Point Address:
  Nancy Lan Guo, West Virginia University Cancer Institute, 2816 HSS, Morgantown, WV 26506-9300, United States
• Email:
  lguo@hsc.wvu.edu
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  EBioMedicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:601a05d867a8ba9623d55c17a3b7efe1b29cffa93a417a7597fe06d4dce94c108760143030430f6308f16c41aebd17f1f8298fe7bb6dc91e23a82b589f051048
• Download URL:
  https://stacks.cdc.gov/view/cdc/211559/cdc_211559_DS1.pdf
• File Type:
  [PDF - 1.16 MB ]