Early detection

Proteomic applications for the early detection of cancer

Key Points

  • Biomarkers are the foundation of cancer detection and monitoring. Most of today's licensed tests for disease detection are protein-based assays.

  • Low-throughput proteomics approaches, such as 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis) coupled with mass spectrometry for protein identification, have proven useful for cancer biomarker discovery, particularly when laser capture microdissection (LCM) is used to isolate cell populations of interest for analysis.

  • Technologies such as multidimensional separation systems directly coupled to mass spectrometry analysis represent improvements in sensitivity and throughput when compared with traditional 2D-PAGE analysis for biomarker discovery.

  • Mass-spectrometry-driven proteomic analysis is a key development for the rapid detection of cancer-specific biomarkers and proteomic patterns of tissue and body fluids.

  • Proteomic pattern diagnostics combines proteomic pattern profiling of tissue and body fluids by mass spectrometry with sophisticated bioinformatics tools to identify patterns within the complex proteomic profile that discriminate between normal, benign or disease states.

  • Proteomic pattern diagnostics has been successfully applied to the problems of early detection for a number of different types of cancer.

  • A number of feasibility, reproducibility and standardization issues need to be addressed before proteomic pattern diagnostics can be incorporated into routine clinical practice.

  • Mass spectrometry might become the preferred detection platform and clinical analyser for routine clinical and medical diagnostics.

Abstract

The ability of physicians to effectively treat and cure cancer is directly dependent on their ability to detect cancers at their earliest stages. Proteomic analyses of early-stage cancers have provided new insights into the changes that occur in the early phases of tumorigenesis and represent a new resource of candidate biomarkers for early-stage disease. Studies that profile proteomic patterns in body fluids also present new opportunities for the development of novel, highly sensitive diagnostic tools for the early detection of cancer.

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Figure 1: Identification and validation of differential expression of transgelin between normal and ductal carcinoma in situ (DCIS) epithelial cells.
Figure 2: Schematic of proteomic pattern diagnostics.
Figure 3: The potential impact of proteomic pattern diagnostics for the early detection of ovarian cancer on 5-year survival statistics.

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Author information

Correspondence to Emanuel F. Petricoin.

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DATABASES

Cancer.gov

bladder cancer

breast cancer

colon cancer

liver cancer

lung cancer

oesophageal cancer

ovarian cancer

prostate cancer

LocusLink

annexin-1

FK506BP

glyoxalase-1

HSP27

PGP9.5

prostate-specific membrane antigen

PSA

RHOGDI

transgelin

FURTHER INFORMATION

Proteomic pattern diagnostics and commercialization potential from Correlogic

Glossary

PROSTATE-SPECIFIC ANTIGEN

The serum level of this protein increases in some men who have prostate cancer or certain benign prostate conditions.

GENOMIC TECHNOLOGIES

Techniques for gene-expression analysis, including oligonucleotide arrays for determining relative levels of expression for thousands of genes between different samples (e.g. normal and tumour) that can lead to the identification of tumour-specific markers.

ELISA (Enzyme-linked, immunosorbent assay).

A sensitive antibody-based method for the detection of an antigen such as a protein.

2D-PAGE

A method for separating proteins by both mass and charge.

MASS SPECTROMETRY

A field that, in its biological applications, uses sophisticated analytical devices to determine the precise molecular weights (mass) of proteins and nucleic acids, as well as the amino-acid sequence of protein molecules.

LASER CAPTURE MICRODISSECTION

A technology that is used for the rapid procurement of a microscopic and pure cellular subpopulation away from its complex tissue milieu, under direct microscopic visualization.

MATRIX COMPOUND

A chemical compound (organic acid) that is used to absorb laser energy and transfer this to biomolecules that are present in the sample, causing them to become protonated and ionized.

IMAGING MASS SPECTROMETRY

An application of a scanning type of mass spectrometry that allows for direct mapping of protein expression profiles that are present in tissue sections or individual cells.

BENIGN PROSTATIC HYPERPLASIA

A non-cancerous condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine.

'DISRUPTIVE' OR 'NON-LINEAR' TECHNOLOGY

A technology that represents a significant, unexpected change in an existing model that does not progress in a straightforward linear fashion, thereby polarizing the existing infrastructure.

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Wulfkuhle, J., Liotta, L. & Petricoin, E. Proteomic applications for the early detection of cancer. Nat Rev Cancer 3, 267–275 (2003). https://doi.org/10.1038/nrc1043

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