Abstract
BackgroundAtypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. Detection of AAH and SCD has been achieved by imaging and bronchoscopy clinically, but sensitivity and specificity remain less than satisfactory. We utilized the ability of the immune system to identify lesion specific proteins for detection of AAH and SCD.MethodsAAH and SCD tissue was surgically removed from six patients of Chinese descent (3 AAH and 3 SCD) with corresponding serum samples. Total RNA was extracted from the tissues and a cDNA library was generated and incorporated into a T7 bacteriophage vector. Following enrichment to remove "normal" reactive phages, a total of 200 AAH related and 200 SCD related phage clones were chosen for statistical classifier development and incorporation into a microarray. Microarray slides were tested with an independent double-blinded population consisting of 100 AAH subjects, 100 SCD subjects and 200 healthy control subjects.ResultsSensitivity of 82% and specificity of 70% were achieved in the detection of AAH using a combination of 9 autoantibody biomarkers. Likewise, 86% sensitivity and 78% specificity were achieved in the detection of SCD using a combination of 13 SCD-associated markers. Sequencing analysis identified that most of these 22 autoantibody biomarkers had known malignant associations.ConclusionsBoth diagnostic values showed promising sensitivity and specificity in detection of pre-neoplastic lung lesions. Hence, this technology could be a useful non-invasive tool to assess lung cancer risk in human populations.
Highlights
Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung
A PCR test was run to determine the sizes of individual phage inserts using T7 primer and the results showed the ranges of the cDNA inserts from both the libraries were from 0.5 ~ 2 Kb, indicating both were good phage libraries
The two libraries were pooled together and biopanned using pooled AAH/SCD and normal serum samples to screen potential tumor-associated antigens expressed by the T7 cDNA phage libraries
Summary
Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. Carcinoma of the lung is the leading cause of morbidity and mortality of human solid cancer worldwide. It accounted for around 12.7% of all new cancer incidences and 18.2% of all cancer mortality, or approximately 1.4 million deaths worldwide in 2008 [1]. In Asia, in China, rising smoking rates cause the incidence of lung cancer to continue to increase. Early detection of lung carcinoma is critical to facilitate successful treatment and increase the chances of survival. Novel techniques which facilitate accurate diagnosis of early malignancy or pre-malignancy would be of great benefit to improve survival rates
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