A novel autoantibody test for the detection of pre-neoplastic lung lesions

Molecular Cancer

Research

Frazer J Lowe¹  Jinchi Zu²  Junfu Li²  Hao Wang²  Weike Shen²  Xufei Zhang³  Li Zhong³ 

[1] British American Tobacco (Investments) Ltd, Group Research and Development, Regents Park Road, SO15 8TL, Millbrook, Southampton, UK;Hebei University, 180 Wusi Rd., Baoding, China;Hebei University, 180 Wusi Rd., Baoding, China;Western University of Health Sciences, 309 E. 2nd St, Pomona, CA, USA;

关键词: Lung cancer;    Smoking;    Biomarker;    Atypical adenomatous hyperplasia;    Squamous cell dysplasia;    Autoantibody;   

DOI  :  10.1186/1476-4598-13-78

 received in 2014-02-13, accepted in 2014-04-01,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Lowe et al.; licensee BioMed Central Ltd. 2014