TY - JOUR
T1 - Identification of serological biomarkers for early diagnosis of lung cancer using a protein array-based approach
AU - Pan, Jianbo
AU - Song, Guang
AU - Chen, Dunyan
AU - Li, Yadong
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. and by the NIH (U24 CA160036-01) to H.Z. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. □S This article contains supplemental material. ¶¶ To whom correspondence should be addressed: Yi Huang, Provincial Clinical College, Fujian Medical University, Fuzhou 350001, Fujian, China. Tel.: +86-591-8821-7895; Fax: +86-591-8753-2356; E-mail: hyi8070@126.com; Jiang Qian, Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Tel.: +1-443-287-3882; Fax: +1-410-502-5382; E-mail: jiang.qian@ jhmi.edu; Heng Zhu, Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. Tel.: +1-410-502-0878; Fax: +1-410-502-1872; E-mail: hzhu4@ jhmi.edu. §§ Jianbo Pan, Guang Song and Dunyan Chen contributed equally to this study.
Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017/12
Y1 - 2017/12
N2 - Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.
AB - Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.
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U2 - 10.1074/mcp.RA117.000212
DO - 10.1074/mcp.RA117.000212
M3 - Article
C2 - 29021294
AN - SCOPUS:85038814584
SN - 1535-9476
VL - 16
SP - 2069
EP - 2078
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 12
ER -