title: Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer.
abstract: Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n=1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (P<0.001), small tumors (P<0.001), estrogen receptor (ER) positivity (P<0.001) and Ki-67 negativity (P<0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P=0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.
authors.affiliation: Department of Laboratory Medicine, Center for Molecular Pathology, Malmö University Hospital, Lund University, Malmö, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Jögi
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.forename: Kristina
authors.initials: K
authors.lastname: Magnusson
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlen
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D016016:Proportional Hazards Models; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C099506:RBM3 protein, human; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen