Validation of Protein Markers for Lung Cancer Using CARET Sera and Proteomics Techniques

Abbreviated Name
Lung CARET
Lead Investigator
Hanash, Samir — The University of Texas MD Anderson Cancer Center
Coordinating Investigator
Zheng, Yingye — Fred Hutchinson Cancer Center
Involved Investigators

Abstract

To validate the finding from pilot studies with CARET sera of autoantibodies to annexins I and II and PGP9.5 as potential biomarkers for lung cancers before the clinical diagnosis, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, histologic type, and smoking status. To determine whether a pattern of occurrence of autoantibodies in lung cancer sera may be diagnostic of lung cancer that is not dependent on the occurrence of any particular autoantibody. To compare the findings for individual biomarker candidates and combinations of biomarker candidates in participants who were current smokers versus former smokers.

Aims

Aim 1: To validate the finding from pilot studies with CARET sera of autoantibodies to annexins I and II and PGP9.5 as potential biomarkers for lung cancers before the clinical diagnosis. Aim 2: To identify additional antigens and antibodies in sera from CARET participants, evaluating sensitivity and specificity by time before diagnosis, treatment arm, gender, and histologic type. Aim 3: To compare the findings for individual biomarker candidates and combinations of biomarker candidates in participants who were current smokers versus former smokers.

Analytic Method

Natural Array technique

Comments

No comments available.

Outcome

Annexin was significantly elevated in lung cancer patients in serum 0-12 months prior to diagnosis (p-value = 0.001) and the area under ROC curve 0.71 with 95% confidence interval from 0.63 to 0.78. The direct clinical utility for Annexin in pre-clinical high risk (heavy smoker) population is unclear as the sensitivity at 90% specificity is 25%, or sensitivity 55% at 80% specificity. However, this validated marker could serve as a member in a panel, yet to be formed, to reach clinical utility for early detection of lung cancer. Lung cancer reference set A specified a PPV of 2.5% would be clinically significant assuming lung cancer incidence among heavy smokers is 1% per year. If we apply 25% sensitivity at 90% specificity in this study, PPV is 2.5%. Note that CARET specimens used in this study were collected within 12 month prior to diagnosis, not at diagnosis. This indicates potential use of Annexin to enrich the high risk smokers for further screening (e.g. CT), though the enrichment is a moderate 2.5 folds. Given Hanash Lab using specimens at diagnosis observed 40-50% sensitivity with near 100% specificity, it seems that the diagnostic performance of Annexin improves as time near diagnosis. Therefore, it is recommended that Annexin should also be validated for its potential clinical use for aiding diagnosis among patients having suspicious lesions in lung (lung cancer reference set B). PGP was not significantly associated with lung cancer in pre-clinical serum. Our findings suggest potential utility of an approach to diagnosis of lung cancer before onset of symptoms that includes screening for autoantibodies to defined antigens

Secure Outcome

No secure outcome available.

Publications

Biomarkers

Data Collections

Start Date
Sep 5 2006
Estimated Finish Date
Jun 1 2009
Finish Date
Jun 1 2009
Protocol ID
138
Protocol Type
Validation
Fields of Research
  • Proteomics
Collaborative Group
Lung and Upper Aerodigestive Cancers Research Group
Cancer Types
  • Malignant neoplasm of bronchus and lung
Phased Status
2

Associated Forms