title: RRM1, TUBB3, TOP2A, CYP19A1, CYP2D6: Difference between mRNA and protein expression in predicting prognosis of breast cancer patients.
abstract: The study investigated the clinical significance of RRM1 (ribonucleoside reductase subunit M1), TUBB3 (tubulin-β-III), TOP2A (DNA topoisomerase II), CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1) and CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) for the diagnosis and possible predictive roles in breast cancer. Tissue microarray detected the expression of RRM1, tubulin-β-III, Topo IIα, CYP19A1 and CYP2D6 protein in breast cancer tissue and tissue adjacent to tumors (TATs). In addition, a publically available tool, was used to assess the prognostic value of their gene expression in breast cancer (http://kmplot.com). Analysis for relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) was performed. Cytoplasmic RRM1, tubulin-β-III, CYP19A1 and Topo IIα staining were significantly higher in breast cancer tissues compared with TATs (P<0.050). Significant correlation occurred between RRM1 expression with pathological classification (P=0.018), lymph node involvement (P=0.035) and ER status (P=0.003). Tubulin-β-III and CYP2D6 expression correlated significantly with tumor grade (P=0.021 for tubulin-β-III and P=0.029 for CYP2D6, respectively). Cox analysis showed that the protein expression of CYP2D6, CYP19A1, RRM1, Topo IIα or tubulin-β-III was not an independent prognostic factor. A significant association occurred between RFS and TUBB3, TOP2A, CYP19A1, and CYP2D6 mRNA expression. With CYP19A1 (P<0.001) and CYP2D6 (P<0.001), a high expression was associated with good clinical outcome. Conversely, a low expression of TUBB3 (P<0.001) and TOP2A (P<0.001) was associated with good clinical outcome. TUBB3 (P=0.0004) and TOP2A (P<0.001) were significant prognostic factors in predicting the patient OS. The expression of RRM1, tubulin-β-III, Topo IIα and CYP19A1 in tumor tissues was significantly higher than that in TATs. TUBB3, TOP2A, CYP19A1 and CYP2D6 gene expression, but not protein expression, was associated with patient survival.
authors.affiliation: Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Xu
authors.affiliation: Department of Oncology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Dai
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Fan
authors.affiliation: Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019389:Cytochrome P-450 CYP2D6 / Q000096:biosynthesis* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D012262:Ribonucleoside Diphosphate Reductase; D046888:Tissue Array Analysis; D014404:Tubulin / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D001141:Aromatase; C561410:CYP19A1 protein, human; D019389:Cytochrome P-450 CYP2D6; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human