Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer

Shadi Ferdosi, Douglas S. Rehder, Paul Maranian, Erik P. Castle, Thai H. Ho, Harvey I. Pass, Daniel W. Cramer, Karen Anderson, Lei Fu, David E.C. Cole, Tao Le, Xifeng Wu, Chad Borges

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    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 α2-6 sialylation, β1-6 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, α2-6 sialylation, β1-4 branching, β1-6 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 α2-6 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.

    Original languageEnglish (US)
    Pages (from-to)543-558
    Number of pages16
    JournalJournal of Proteome Research
    Volume17
    Issue number1
    DOIs
    StatePublished - Jan 5 2018

    Fingerprint

    Polysaccharides
    Plasmas
    Serum
    Neoplasms
    Lung Neoplasms
    Tumors
    Glycomics
    Liver
    Hazards
    Pancreatic Neoplasms
    Proportional Hazards Models
    Tissue
    Liver Cirrhosis
    Prostate
    Autopsy
    Smoking
    Survival

    Keywords

    • branching
    • cancer
    • fucosylation
    • glycans
    • plasma
    • progression
    • serum
    • sialylation
    • smoking
    • survival

    ASJC Scopus subject areas

    • Biochemistry
    • Chemistry(all)

    Cite this

    Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer. / Ferdosi, Shadi; Rehder, Douglas S.; Maranian, Paul; Castle, Erik P.; Ho, Thai H.; Pass, Harvey I.; Cramer, Daniel W.; Anderson, Karen; Fu, Lei; Cole, David E.C.; Le, Tao; Wu, Xifeng; Borges, Chad.

    In: Journal of Proteome Research, Vol. 17, No. 1, 05.01.2018, p. 543-558.

    Research output: Contribution to journalArticle

    Ferdosi, Shadi ; Rehder, Douglas S. ; Maranian, Paul ; Castle, Erik P. ; Ho, Thai H. ; Pass, Harvey I. ; Cramer, Daniel W. ; Anderson, Karen ; Fu, Lei ; Cole, David E.C. ; Le, Tao ; Wu, Xifeng ; Borges, Chad. / Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer. In: Journal of Proteome Research. 2018 ; Vol. 17, No. 1. pp. 543-558.
    @article{df337571c5084dc4ad058bfdeaf6154e,
    title = "Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer",
    abstract = "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 α2-6 sialylation, β1-6 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, α2-6 sialylation, β1-4 branching, β1-6 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 α2-6 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.",
    keywords = "branching, cancer, fucosylation, glycans, plasma, progression, serum, sialylation, smoking, survival",
    author = "Shadi Ferdosi and Rehder, {Douglas S.} and Paul Maranian and Castle, {Erik P.} and Ho, {Thai H.} and Pass, {Harvey I.} and Cramer, {Daniel W.} and Karen Anderson and Lei Fu and Cole, {David E.C.} and Tao Le and Xifeng Wu and Chad Borges",
    year = "2018",
    month = "1",
    day = "5",
    doi = "10.1021/acs.jproteome.7b00672",
    language = "English (US)",
    volume = "17",
    pages = "543--558",
    journal = "Journal of Proteome Research",
    issn = "1535-3893",
    publisher = "American Chemical Society",
    number = "1",

    }

    TY - JOUR

    T1 - Stage Dependence, Cell-Origin Independence, and Prognostic Capacity of Serum Glycan Fucosylation, β1-4 Branching, β1-6 Branching, and α2-6 Sialylation in Cancer

    AU - Ferdosi, Shadi

    AU - Rehder, Douglas S.

    AU - Maranian, Paul

    AU - Castle, Erik P.

    AU - Ho, Thai H.

    AU - Pass, Harvey I.

    AU - Cramer, Daniel W.

    AU - Anderson, Karen

    AU - Fu, Lei

    AU - Cole, David E.C.

    AU - Le, Tao

    AU - Wu, Xifeng

    AU - Borges, Chad

    PY - 2018/1/5

    Y1 - 2018/1/5

    N2 - 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 α2-6 sialylation, β1-6 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, α2-6 sialylation, β1-4 branching, β1-6 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 α2-6 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.

    AB - 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 α2-6 sialylation, β1-6 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, α2-6 sialylation, β1-4 branching, β1-6 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 α2-6 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.

    KW - branching

    KW - cancer

    KW - fucosylation

    KW - glycans

    KW - plasma

    KW - progression

    KW - serum

    KW - sialylation

    KW - smoking

    KW - survival

    UR - http://www.scopus.com/inward/record.url?scp=85040174649&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85040174649&partnerID=8YFLogxK

    U2 - 10.1021/acs.jproteome.7b00672

    DO - 10.1021/acs.jproteome.7b00672

    M3 - Article

    VL - 17

    SP - 543

    EP - 558

    JO - Journal of Proteome Research

    JF - Journal of Proteome Research

    SN - 1535-3893

    IS - 1

    ER -