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Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum
Open accessAbstract
Genetic alterations in tumor cells often lead to the emergence of growth-stimulatory autocrine and paracrine signals, involving overexpression of secreted peptide growth factors, cytokines, and hormones. Increased levels of these soluble proteins may be exploited for cancer diagnosis and management or as points of therapeutic intervention. Here, we combined the use of controlled vocabulary terms and sequence-based algorithms to predict genes encoding secreted proteins from among approximately 12,500 sequences represented on oligonucleotide microarrays. Expression of these genes was queried in 150 carcinomas from 10 anatomic sites of origin and compared with 46 normal tissues derived from the corresponding sites of tumor origin and other body tissues and organs. Of 74 different genes identified as overexpressed in cancer tissues, several encode proteins with demonstrated clinical diagnostic application, such as alpha-fetoprotein in liver carcinoma, and kallikreins 6 and 10 in ovarian cancer, or therapeutic utility, such as gastrin-releasing peptide/bombesin in lung carcinomas. We show that several of the other candidate genes encode proteins with high levels of tumor-associated expression by immunohistochemistry on tissue microarrays and further demonstrate significantly elevated levels of another novel candidate protein, macrophage inhibitory cytokine 1, a distant member of the transforming growth factor-beta superfamily, in the serum of patients with metastatic prostate, breast, and colorectal carcinomas. Our results suggest that the combination of annotation/protein sequence analysis, transcript profiling, immunohistochemistry, and immunoassay is a powerful approach for delineating candidate biomarkers with potential clinical significance and may be broadly applicable to other human diseases.
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“Elevated levels of GDF15 have been linked to tumor growth and poor prognosis in cancer patients raising the question as to whether GDF15 serves as a tumor suppressor or promoter and a target for the treatment of cancer (84, 85, 99).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [99]
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Metadata
- Authors
- Welsh, J. B., Sapinoso, L. M., Kern, S. G., Brown, D. A., Liu, T., Bauskin, A. R., Ward, R. L., Hawkins, N. J., Quinn, D. I., Russell, P. J., Sutherland, R. L., Breit, S. N., Moskaluk, C. A., Frierson, H. F., & Hampton, G. M.
- Affiliations
- Genomics Institute of the Novartis Research Foundation (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-03-06
- Volume
- 100
- Issue
- 6
- Pages
- 3410-3415
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC152306
- OpenAlex
- W2155470210
- Cited by
- 503
- References
- 38
- Citations by year
- 2026: 8 · 2025: 23 · 2024: 30 · 2023: 24 · 2022: 22 · 2021: 22 · 2020: 28 · 2019: 15 · 2018: 17 · 2017: 21 · 2016: 14 · 2015: 18 · 2014: 21 · 2013: 22 · 2012: 29
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- secreted proteins, tumor markers, gene overexpression, oligonucleotide microarrays, gene expression profiling, cytokines, growth factors, alpha-fetoprotein, kallikrein, gastrin-releasing peptide, MIC-1, TGF-beta superfamily, serum biomarkers, metastatic carcinoma, cancer diagnosis
- MeSH terms
- Female, Humans, Male, Neoplasm Metastasis, Neoplasm Proteins, Neoplasms, Biomarkers, Tumor, Cytokines, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Growth Differentiation Factor 15
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