Cancer Proteomics

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1. Impact of Proteomics on Cancer Research

Cancer is a disease of gene, and the genomic aberrations across entire chromosomes transform the normal cells into fully malignant tumor cells (Figure 1). The genomic aberrations finally govern the clinico-pathological behaviors of tumor cells, and indeed the cancer classifications based on the genomic alterations reflect the clinical characters. However, the genomic features may not always determine the aberrant contents of mRNA and proteins. For instance, mRNA levels are not necessary parallel with the copy number of genes and the degree of DNA methylation. The discordance between mRNA and protein level has been reported in many publications. Presently, genomic information cannot predict the unique characters of proteins such as posttranslational modification, enzyme activities and functionalities, celluar and tissue localization, and complex with the other molecules. On the other hand, these many lines of evidence suggested that the aberrations of such protein characters were highly correlated with malignant potential of tumor cells. Taken together, proteome information is indispensable to understand the functional interpretation of genomic information, and proteomics will tell us how the genomic abnormalities affect the cancer phenotypes.


Figure 1 Genomic information is transcribed to mRNA, translated into proteins, then finally determines the cellular phenotypes. Proteome works just behind cancer phenotypes, and thus proteomics is a powerful approach for functional interpretation of genome and cancer research.

Proteomics is characterized as a global and genome wide protein study, revealing the aberrations at protein level and their commitments in the cancer onset and progression. The final goal of our proteomic research is the improvement of cancer prevention, diagnosis and treatment using research results.


Figure 2 Workflow of cancer proteomics in the project. Our cancer proteomics reveals the fundamental mechanisms of carcinogenesis and cancer progression, and benefits the cancer patients.

2. Current Status of Cancer Proteomics

The fruitful results of human genome project and dramatic progression of various technologies for molecular biology gave a reality to global study of proteins. Major research theme in cancer proteomics are 1) understanding of molecular mechanisms of carcinogenesis and cancer progression, 2) identification of therapeutic targets, and 3) discovery of biomarkers. Popular technologies used in cancer proteomics include two-dimensional gel electrophoresis, mass spectrometry, array technology, and liquid chromatography. Each technology has its own advantage and disadvantage, and any single technologies are not absolutely superior to the others. Selected or combined use of these technologies depending on the research purpose and circumstances is the common strategies in cancer proteomics.

Technologies for sample preparations are also crucial in proteomics. The reproducible protein extraction will be essential for the proteins competent to degradation. The devices for selective cell recovery will be essential for precious protein expression study as the tumor tissues include various type of cells. High sensitive fluorescent reagents to observe the minute amount of proteins and isotope reagents for quantitative comparison play an important role in proteomic study. Many products are commercially available, and the detailed protocols and the results of combined use are published in technical reports. As is the case of proteomic approach, none of them has absolute advantage over the others, and the purpose of experiments determines the best use of each method.

3. Future View of Cancer Proteomics

Proteomics becomes a popular approach in cancer research, resulting in numerous publications. Next challenge should be a practical application of proteomics results. For instance, the biomarker development requires statistical validation, functional validation and clinical validation using a large-scale clinical sample set, and simple examination devices for established biomarkers. These practical notions should be kept in mind at the early stage of biomarker development.

Principal of proteomics is a comprehensive understanding of all expressed proteins. However, existing proteomic modalities and their combinations uncover only a limited portion of proteome. In addition to the efforts toward clinical application of proteomics results, optimization of existing methods and establishment of novel technologies should be undertaken for a while. Any single proteomic modalities may not complete proteomic study, reasoning that the combined use of multiple technologies will be a solution.

Genomic alterations should exist behind proteomic aberrations. Integrative studies combining genome, transcriptome and proteome will lead a paradigm of cancer research. Combined use of clinico-pathological information may facilitate our further understanding of molecular background of cancer diversity, identification of drug target, and development of novel biomarkers.