title: CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma.
abstract: CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that negatively regulates TGF-β signaling. CD109 was originally identified in hematopoietic tumors; however, the significance of CD109 in hematopoietic malignancies remains unclear. Here, we study the association of CD109 with diffuse large B-cell lymphoma (DLBCL) prognosis. Eighty-four DLBCL specimens were immunohistochemically analyzed for CD109 expression, and 31 and 53 cases were classified into low- and high-CD109 expression groups, respectively. CD109 expression was not associated with overall survival using the Kaplan-Meier analysis and log-rank tests (P = 0.17); however, a significant association was observed between high-CD109 expression and low-1-year survival (P = 0.01). Moreover, in combination with the revised International Prognostic Index (R-IPI), R-IPI-poor/CD109-high was associated with poorer prognosis compared with R-IPI-poor alone. We assessed TGF-β signaling in CD109-depleted Nalm6 cells (a human B-lymphoblastic leukemia/lymphoma cell line), and found prolonged Smad2 phosphorylation compared with control cells after TGF-β1 stimulation, suggesting that CD109 attenuates TGF-β1 signaling in human B-cell tumors. These results suggest that CD109 is a putative biomarker for identifying a high-risk group among DLBCL patients.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.|Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ichinoe
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.|Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Sosei
authors.initials: S
authors.lastname: Okina
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nakada
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagisawa
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Shi-Xu
authors.initials: SX
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Numata
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Department of Transfusion and Cell Transplantation, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. murakumo@med.kitasato-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D012306:Risk; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta
keywords: CD109; Diffuse large B-cell lymphoma; Prognosis; TGF-β signaling