TY - JOUR
T1 - Integration of IgA and IgG autoantigens improves performance of biomarker panels for early diagnosis of lung cancer
AU - Pan, Jianbo
AU - Yu, Lili
AU - Wu, Qingwei
AU - Lin, Xiaoqing
AU - Liu, Shuang
AU - Hu, Shaohui
AU - Rosa, Christian
AU - Eichinger, Daniel
AU - Pino, Ignacio
AU - Zhu, Heng
AU - Qian, Jiang
AU - Huang, Yi
N1 - Funding Information:
* This work was supported in part by the National Natural Science Foundation Emergency Management Project (No. 81541063 to Y.H.), Joint Fund of Science and Technology Innovation of Fujian province (No. 2017Y9069 to Y.H.), Scientific Joint Fund of High Level Hospital Construction of Fujian provincial Hospital (No. 2017LHJJ04 to Y.H.), the NIH (U24 CA160036-01 to H.Z.), and CDI Laboratories Inc. This study was partially funded by CDI Laboratories. I.P., D.E., C.R., and S.H. are full-time CDI employees. H.Z. is a co-founder of CDI. J.Q. and H.Z. are CDI consultants. □S This article contains supplemental Figures and Tables. ¶¶ To whom correspondence may be addressed. Tel.: +86-591-8821-7895; Fax: +86-591-8753-2356; E-mail: hyi8070@126.com. ‡‡‡ To whom correspondence may be addressed. E-mail: ignacio.pino@cdi-lab.com. ‖‖ Jianbo Pan, Lili Yu and Qingwei Wu contributed equally to this work.
Publisher Copyright:
© 2020 Pan et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2020
Y1 - 2020
N2 - Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.
AB - Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.
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U2 - 10.1074/mcp.RA119.001905
DO - 10.1074/mcp.RA119.001905
M3 - Article
C2 - 31924693
AN - SCOPUS:85081073604
SN - 1535-9476
VL - 19
SP - 490
EP - 500
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 3
ER -