Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of colorectal cancer

Chung-Wei Fan; Yung-Bin Kuo; Geng-Pin Lin; Si-Min Chen; Shih-Hsien Chang; Bo-An Li; Err-Cheng Chan

doi:10.1016/j.cca.2017.10.022

Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of colorectal cancer

Clin Chim Acta. 2017 Dec:475:157-163. doi: 10.1016/j.cca.2017.10.022. Epub 2017 Oct 23.

Authors

Chung-Wei Fan¹, Yung-Bin Kuo², Geng-Pin Lin³, Si-Min Chen⁴, Shih-Hsien Chang⁴, Bo-An Li⁵, Err-Cheng Chan⁶

Affiliations

¹ Division of Colorectal Surgery, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Taoyuan, Taiwan.
² Genpronex Biomedical Inc, Taiwan.
³ Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁴ Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
⁵ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
⁶ Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan. Electronic address: chanec@mail.cgu.edu.tw.

PMID: 29074220
DOI: 10.1016/j.cca.2017.10.022

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and early diagnosis is vital to improving prognoses. We explored the diagnostic potential of a multiplex autoantibody panel as a biomarker for the detection of CRC by ELISA.

Methods: In total, 192 serum samples (92 CRC and 100 matched controls) were tested against a panel of 12 tumor-associated antigens (TAAs): RPH3AL, RPL36, SLP2, p53, survivin, ANAXA4, SEC61B, CCCAP, NYCO16, NMDAR, PLSCR1, and HDAC5. Individual and combined autoantibody signatures were examined.

Results: Compared to individual autoantibody markers, the combinations of TAAs provided better discrimination between tumorous and normal sera. The overall sensitivity of a selected panel of four antibodies (anti-SLP2, -p53, -SEC61B, and -PLSCR1) was 64.1%, with a specificity of 80% that increased to 83.7% when carcinoembryonic antigen (CEA) measurement was added. Furthermore, the sensitivity of the panel of four antibodies for early and advanced stages of CRC was 66.7% and 62%, increasing to 88.3% and 84%, respectively, when CEA was added.

Conclusions: We identified a panel of four antibodies as a promising diagnostic biomarker for the detection of CRC.

Keywords: Autoantibody; Biomarker; Colorectal cancer.

MeSH terms

Adult
Aged
Aged, 80 and over
Antigens, Neoplasm / genetics*
Antigens, Neoplasm / immunology
Autoantibodies / blood*
Biomarkers, Tumor / blood*
Blood Proteins / genetics
Blood Proteins / immunology
Carcinoembryonic Antigen / genetics
Carcinoembryonic Antigen / immunology
Case-Control Studies
Colorectal Neoplasms / blood
Colorectal Neoplasms / diagnosis*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / immunology
Early Detection of Cancer / methods
Female
Humans
Immunoassay*
Male
Membrane Proteins / genetics
Membrane Proteins / immunology
Middle Aged
Neoplasm Staging
Phospholipid Transfer Proteins / genetics
Phospholipid Transfer Proteins / immunology
Prognosis
SEC Translocation Channels / genetics
SEC Translocation Channels / immunology
Sensitivity and Specificity
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / immunology

Substances

Antigens, Neoplasm
Autoantibodies
Biomarkers, Tumor
Blood Proteins
Carcinoembryonic Antigen
Membrane Proteins
PLSCR1 protein, human
Phospholipid Transfer Proteins
SEC Translocation Channels
SEC61B protein, human
STOML2 protein, human
Tumor Suppressor Protein p53