期刊
JOURNAL OF PROTEOME RESEARCH
卷 17, 期 1, 页码 543-558出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.7b00672
关键词
glycans; cancer; plasma; serum; fucosylation; sialylation; branching; smoking; progression; survival
资金
- Flinn Foundation [1977]
- Gerstner Family Career Development Award
- Gloria A. and Thomas J. Dutson Jr. Kidney Research Endowment
- University of Texas MD Anderson Cancer Center
- Center for Translational and Public Health Genomics
- National Cancer Institute of the National Institutes of Health [R33 CA191110, P50 CA070907, R01 CA176568]
Glycans represent a promising but only marginally accessed source of cancer markers. We previously reported the development of a molecularly bottom-up approach to plasma and serum (P/S) glycomics based on glycan linkage analysis that captures features such as alpha 2-6 sialylation, beta 1-6 branching, and core fucosylation as single analytical signals. Based on the behavior of P/S glycans established to date, we hypothesized that the alteration of P/S glycans observed in cancer would be independent of the tissue in which the tumor originated yet exhibit stage dependence that varied little between cancers classified on the basis of tumor origin. Herein, the diagnostic utility of this bottom-up approach as applied to lung cancer patients (n = 127 stage I; n = 20 stage II; n = 81 stage III; and n = 90 stage IV) as well as prostate (n = 40 stage II), serous ovarian (n = 59 stage III), and pancreatic cancer patients (n = 15 rapid autopsy) compared to certifiably healthy individuals (n = 30), nominally healthy individuals (n = 166), and risk-matched controls (n = 300) is reported. Diagnostic performance in lung cancer was stage-dependent, with markers for terminal (total) fucosylation, alpha 2-6 sialylation, beta 1-4 branching, beta 1-6 branching, and outer-arm fucosylation most able to differentiate cases from controls. These markers behaved in a similar stage-dependent manner in other types of cancer as well. Notable differences between certifiably healthy individuals and case-matched controls were observed. These markers were not significantly elevated in liver fibrosis. Using a Cox proportional hazards regression model, the marker for alpha 2-6 sialylation was found to predict both progression and survival in lung cancer patients after adjusting for age, gender, smoking status, and stage. The potential mechanistic role of aberrant P/S glycans in cancer progression is discussed.
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