title: Identification of recurrence-related microRNAs in the bone marrow of breast cancer patients.
abstract: Recently, bone marrow has been considered as playing a critical role in the generation of both metastasis and recurrent disease. The accumulation of a single microRNA in the bone marrow has the potential to regulate the translation of multiple genes in cancer metastasis and may therefore serve as a prognostic marker for cancer recurrence. MicroRNA microarray analysis was performed to compare microRNA levels in bone marrow from 4 breast cancer patients with recurrent disease and 4 patients without recurrence. Accumulation of two of these microRNAs, miR-21 and miR-181a, in the recurrent breast cancer cases was validated by RT-PCR in bone marrow from 291 additional breast cancer cases. Expression of a common target gene, PDCD4, was also determined in bone marrow from 291 breast cancer cases. Increased miR-21 and miR-181a levels were significantly associated with shortened disease-free survival (DFS; p=0.0003, 0.0007) and overall survival (OS; p=0.0351, 0.0443), respectively. While low PDCD4 expression was also significantly associated with poorer DFS (p=0.036). Multivariate analysis identified bone marrow miR-21 and mR-181a levels as valuable independent prognostic factors, with correlation coefficients that were significantly higher than that of the transcript of their common target gene. Accumulation of miR-21 and miR-181a in bone marrow appears to be associated with prognosis in breast cancer patients. The much higher significant correlation with microRNA levels and prognosis suggests epistatic effects on multiple target genes in the bone marrow of breast cancer patients.
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation Kyushu University, Beppu, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ota
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Akemi
authors.initials: A
authors.lastname: Kataoka
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C524940:MIRN21 microRNA, human; C540193:MIrn181 microRNA, human; C114487:PDCD4 protein, human