title: Improving Detection Accuracy of Lung Cancer Serum Proteomic Profiling via Two-Stage Training Process.
abstract: BACKGROUND
  Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) is a frequently used technique for cancer biomarker research. The specificity of biomarkers detected by SELDI can be influenced by concomitant inflammation. This study aimed to increase detection accuracy using a two-stage analysis process.
  
  
  METHODS
  Sera from 118 lung cancer patients, 72 healthy individuals, and 31 patients with inflammatory disease were randomly divided into training and testing groups by 3:2 ratio. In the training group, the traditional method of using SELDI profile analysis to directly distinguish lung cancer patients from sera was used. The two-stage analysis of distinguishing the healthy people and non-healthy patients (1st-stage) and then differentiating cancer patients from inflammatory disease patients (2nd-stage) to minimize the influence of inflammation was validated in the test group.
  
  
  RESULTS
  In the test group, the one-stage method had 87.2% sensitivity, 37.5% specificity, and 64.4% accuracy. The two-stage method had lower sensitivity (> 70.1%) but statistically higher specificity (80%) and accuracy (74.7%). The predominantly expressed protein peak at 11480 Da was the primary splitter regardless of one- or two-stage analysis. This peak was suspected to be SAA (Serum Amyloid A) due to the similar m/z countered around this area. This hypothesis was further tested using an SAA ELISA assay.
  
  
  CONCLUSIONS
  Inflammatory disease can severely interfere with the detection accuracy of SELDI profiles for lung cancer. Using a two-stage training process will improve the specificity and accuracy of detecting lung cancer.
authors.affiliation: Division of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. M002047@ms.skh.org.tw.
authors.forename: Pei-Sung
authors.initials: PS
authors.lastname: Hsu
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Wang
authors.forename: Su-Chen
authors.initials: SC
authors.lastname: Huang
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Lin
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Chang
authors.forename: Yuk-Wah
authors.initials: YW
authors.lastname: Tsang
authors.forename: Jiunn-Song
authors.initials: JS
authors.lastname: Jiang
authors.forename: Shang-Jyh
authors.initials: SJ
authors.lastname: Kao
authors.forename: Wu-Ching
authors.initials: WC
authors.lastname: Uen
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Chi