Confirmation of Gene Expression-Based Prediction of Survival in Non-Small Cell Lung Cancer

Details

• Personal Author:
  Beer DG ; Castranova, Vincent ; Dowlati A ; Flynn DC ; Guo NL ; Lin H ; Msiska Z ; Qian Y ; Remick SC ; Shi X ; Tosun K ; Vallyathan V ; Wan YW
• Description:
  Purpose: It is a critical challenge to determine the risk of recurrence in early stage non-small cell lung cancer (NSCLC) patients. Accurate gene expression signatures are needed to classify patients into high- and low-risk groups to improve the selection of patients for adjuvant therapy. Experimental Design: multiple published microarray data sets were used to evaluate our previously identified lung cancer prognostic gene signature. Expression of the signature genes was further validated with real-time reverse transcription-PCR and Western blot assays of snap-frozen lung cancer tumor tissues. Results: our previously identified 35-gene signature stratified 264 patients with NSCLC into high- and low-risk groups with distinct overall survival rates (P < 0.05, Kaplan-Meier analysis, log-rank tests). The 35-gene signature further stratified patients with clinical stage 1A diseases into poor prognostic and good prognostic subgroups (P = 0.0007, Kaplan-Meier analysis, log-rank tests). This signature is independent of other prognostic factors for NSCLC, including age, sex, tumor differentiation, tumor grade, and tumor stage. The expression of the signature genes was validated with real-time reverse transcription-PCR analysis of lung cancer tumor specimens. Protein expression of two signature genes, TAL2 and ILF3, was confirmed in lung adenocarcinoma tumors by using Western blot analysis. These two biomarkers showed correlated mRNA and protein overexpression in lung cancer development and progression. Conclusions: the results indicate that the identified 35-gene signature is an accurate predictor of survival in NSCLC. It provides independent prognostic information in addition to traditional clinicopathologic criteria. [Description provided by NIOSH]
• Subjects:
  Biological Factors Biomarkers Carcinogens Diagnosis Genetics Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Adenocarcinomas Biological-factors Cancer-rates Cell-biology Cellular-function Cellular-reactions Clinical-diagnosis Genes Genetic-factors Lung-cells Lung-disease Mathematical-models Pulmonary-system-disorders Statistical-analysis Treatment Tumorigenesis Tumorigens Tumors

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• ISSN:
  1078-0432
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  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
• Volume:
  14
• Issue:
  24
• NIOSHTIC Number:
  nn:20034852
• Citation:
  Clin Cancer Res 2008 Dec; 14(24):8213-8220
• Contact Point Address:
  Nancy L. Guo, Mary Babb Randolph Cancer Center/Department of Community Medicine, West Virginia University, 1814 HSS, 1 Medical Center Drive, Morgantown, WV 26506-9300
• Email:
  lguo@hsc.wvu.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Clinical Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:31d2752f03eefc17adf2ec444ee77e9a4b2a72e076c7bd0f334ed83fc502e3a79a619efc94662b43e2125a5a3544e2e069e73bda9a340b4a66274b3ee55cd966
• Download URL:
  https://stacks.cdc.gov/view/cdc/186905/cdc_186905_DS1.pdf
• File Type:
  [PDF - 496.04 KB ]