title: RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer.
abstract: BACKGROUND
  We have previously described the essential role of the retinoid-inducible nuclear factor (RINF) during differentiation of hematopoietic cells and suggested its putative involvement in myeloid leukemia and preleukemia. Here, we have investigated whether this gene could have a deregulated expression in malignant tissues compared with their normal tissues of origin and if this potential deregulation could be associated with important clinicopathological parameters.
  
  
  METHODS
  RINF messenger RNA expression was examined in biopsies from locally advanced breast tumors, metastatic malignant melanomas, and papillary thyroid carcinomas and compared with their paired or nonpaired normal reference samples. Further, the prognostic role of RINF expression was evaluated in locally advanced breast cancer.
  
  
  RESULTS
  RINF expression was significantly higher in all tumor forms (primary breast, and thyroid cancers and metastatic melanomas) as compared with normal control tissues (P < 0.001 for each comparison). Importantly, high levels of RINF expression correlated to a poor overall survival in breast cancer (P = 0.013). This finding was confirmed in three independent public microarray datasets (P = 0.043, n = 234; P = 0.016, n = 69; P = 0.001, n = 196) and was independent of tamoxifen therapy. Notably, high levels of RINF was strongly associated with TP53 wild-type status (P = 0.002) possibly indicating that high levels of RINF could substitute for TP53 mutations as an oncogenic mechanism during the malignant development of some cases of breast cancer.
  
  
  CONCLUSIONS
  Our data indicate that (i) RINF overexpression is associated with the malignant phenotype in solid tumors and (ii) RINF overexpression represents an independent molecular marker for poor prognosis in breast tumors.
authors.affiliation: Department of Molecular Biology, University of Bergen, Bergen, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Knappskog
authors.forename: L M
authors.initials: LM
authors.lastname: Myklebust
authors.forename: C
authors.initials: C
authors.lastname: Busch
authors.forename: T
authors.initials: T
authors.lastname: Aloysius
authors.forename: J E
authors.initials: JE
authors.lastname: Varhaug
authors.forename: P E
authors.initials: PE
authors.lastname: Lønning
authors.forename: J R
authors.initials: JR
authors.lastname: Lillehaug
authors.forename: F
authors.initials: F
authors.lastname: Pendino
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D018628:Gene Dosage; D016158:Genes, p53; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C540448:CXXC5 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53