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Review
. 2017 Aug 18;7(14):3559-3572.
doi: 10.7150/thno.20797. eCollection 2017.

Mass spectrometry-assisted gel-based proteomics in cancer biomarker discovery: approaches and application

Rongrong Huang  1 , Zhongsi Chen  1 , Lei He  1 , Nongyue He  1   2 , Zhijiang Xi  3 , Zhiyang Li  1   4 , Yan Deng  1   2 , Xin Zeng  5
Affiliations
Review

Mass spectrometry-assisted gel-based proteomics in cancer biomarker discovery: approaches and application

Rongrong Huang et al. Theranostics. .

Abstract

There is a critical need for the discovery of novel biomarkers for early detection and targeted therapy of cancer, a major cause of deaths worldwide. In this respect, proteomic technologies, such as mass spectrometry (MS), enable the identification of pathologically significant proteins in various types of samples. MS is capable of high-throughput profiling of complex biological samples including blood, tissues, urine, milk, and cells. MS-assisted proteomics has contributed to the development of cancer biomarkers that may form the foundation for new clinical tests. It can also aid in elucidating the molecular mechanisms underlying cancer. In this review, we discuss MS principles and instrumentation as well as approaches in MS-based proteomics, which have been employed in the development of potential biomarkers. Furthermore, the challenges in validation of MS biomarkers for their use in clinical practice are also reviewed.

Keywords: cancer biomarkers; mass spectrometry; proteomics.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Schematic illustration of biomarkers for various types of cancers. Biomarkers are quantitative indicators of a specific biological state; therefore, cancer-associated biomarkers are useful for understanding the molecular basis of disease, early detection, identifying patients at different clinical stages, and developing a personal therapy.
Figure 2
Figure 2
Timeline of progress in proteomics.
Figure 3
Figure 3
Schematic representation of the various stages in the biomarker pipeline. SISCAPA is the acronym for Stable Isotope Standards and Capture by Antipeptide Antibodies. FISH is short for fluorescent in situ hybridization.
Figure 4
Figure 4
Two categories of proteomic experiments.
Figure 5
Figure 5
SRM technique.
Figure 6
Figure 6
(A) Schematic illustration of proteome screening of pleural effusions to identify biomarkers for NSCLC. 1D SDS-PAGE was performed to separate proteins in pleural fluids. ELISA was used for the validation of protein candidates. (B) Schematic diagram of the experimental design. Normal, para-tumor-, and tumor-derived cluster of differentiation (CD) 105+ endothelial cells (ECs) were isolated, followed by iTRAQ-2DLC-MS/MS-based protein abundance profiling and comparative analysis of profiles. (C) Schematic diagram of the experimental design of systematic comparison between various quantitative methods for quantification of proteins within one pathway. (D) Schematic diagram of the experimental design for the isolation and characterization of urinary exosomes.
Figure 7
Figure 7
Schematic illustration of potential reasons for failure of biomarkers in clinical practice.
See this image and copyright information in PMC

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