Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays

Wanlei Gao; Wentao Wang; Shihua Yao; Shan Wu; Honglian Zhang; Jishen Zhang; Fengxiang Jing; Hongju Mao; Qinghui Jin; Hui Cong; Chunping Jia; Guojun Zhang; Jianlong Zhao

doi:10.1016/j.aca.2016.12.016

Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays

Anal Chim Acta. 2017 Mar 15:958:77-84. doi: 10.1016/j.aca.2016.12.016. Epub 2016 Dec 26.

Authors

Wanlei Gao¹, Wentao Wang², Shihua Yao³, Shan Wu⁴, Honglian Zhang⁵, Jishen Zhang⁵, Fengxiang Jing⁵, Hongju Mao⁵, Qinghui Jin⁵, Hui Cong⁶, Chunping Jia⁷, Guojun Zhang⁸, Jianlong Zhao⁵

Affiliations

¹ State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
² State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; The department of Respiratory Medicine of The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
³ Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
⁴ State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
⁵ State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
⁶ Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
⁷ State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China. Electronic address: jiachp@mail.sim.ac.cn.
⁸ The department of Respiratory Medicine of The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: zlgj-001@126.com.

PMID: 28110687
DOI: 10.1016/j.aca.2016.12.016

Abstract

Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl₄ and H₂O₂, and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL^-1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer.

Keywords: Gold deposition; Gold nanoparticles; Lung cancer; Microarray; Tumor marker.

MeSH terms

Antigens, Neoplasm / analysis
Biomarkers, Tumor / analysis*
Carcinoembryonic Antigen / analysis
Gold*
Humans
Hydrogen Peroxide
Keratin-19 / analysis
Lung Neoplasms / diagnosis*
Metal Nanoparticles*

Substances

Antigens, Neoplasm
Biomarkers, Tumor
Carcinoembryonic Antigen
Keratin-19
antigen CYFRA21.1
Gold
Hydrogen Peroxide