Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer.

Abstract:

:In this study, we quantified 249 mature micro-RNA (miRNA) transcripts in estrogen receptor-positive (ER(+)) primary breast tumors of patients with lymph node-negative (LNN) disease to identify miRNAs associated with metastatic capability. In addition, the prognostic value of the candidate miRNAs was determined in ER(-)/LNN breast cancer. Unsupervised analysis in a prescreening set of 38 patients identified three subgroups predominantly driven by three miRNA signatures: an ER-driven luminal B-associated miRNA signature, a stromal miRNA signature, and an overexpressed miRNA cluster located on chromosome 19q23, but these intrinsic miRNA signatures were not associated with tumor aggressiveness. Supervised analysis in the initial subset and subsequent analysis in additional tumors significantly linked four miRNAs (miR-7, miR-128a, miR-210, and miR-516-3p) to ER(+)/LNN breast cancer aggressiveness (n = 147) and one miRNA (miR-210) to metastatic capability in ER(-)/LNN breast cancer (n = 114) and in the clinically important triple-negative subgroup (n = 69) (all P < 0.05). Bioinformatic analysis coupled miR-210 to hypoxia/VEGF signaling, miR-7 and miR-516-3p to cell cycle progression and chromosomal instability, and miR-128a to cytokine signaling. In conclusion, our work connects four miRNAs to breast cancer progression and to several distinct biological processes involved therein.

authors

Foekens JA,Sieuwerts AM,Smid M,Look MP,de Weerd V,Boersma AW,Klijn JG,Wiemer EA,Martens JW

doi

10.1073/pnas.0803304105

subject

Has Abstract

pub_date

2008-09-02 00:00:00

pages

13021-6

issue

35

eissn

0027-8424

issn

1091-6490

pii

0803304105

journal_volume

105

pub_type

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