Dataset Information

High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer.

ABSTRACT:

Introduction

Altered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).

Experimental design

In this prospective study, we measured miR-21, miR-10b, and miR-19a levels using quantitative reverse transcriptase-polymerase chain reaction in the serum of 113 breast cancer patients and determined their association with clinicopathologic factors and clinical outcome. Thirty healthy donors with no history of cancer were enrolled as controls.

Results

Patients with non-metastatic HER2(+) breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2(-) disease (p?=?0.044); whereas patients with metastatic HER2(+) breast cancer had higher serum miR-10b median levels than patients with metastatic HER2(-) disease (p?=?0.0004). There were no significant differences in serum miR-19a median levels between HER2(+) and HER2(-) groups, regardless of the presence of metastases. High serum miR-19a levels were associated with IBC (p?=?0.039). Patients with metastatic IBC had significantly higher serum miR-19a median levels than patients with metastatic non-IBC (p?=?0.019). Finally, high serum miR-19a levels were associated with longer progression-free survival time (10.3 vs. 3.2 months; p?=?0.022) and longer overall survival time (median not reached vs. 11.2 months; p?=?0.003) in patients with metastatic HER2(+) IBC.

Conclusion

High levels of miR-21 and miR-10b were present in the serum of patients with non-metastatic and metastatic HER2(+) breast cancer, respectively. High levels of serum miR-19a may represent a biomarker for IBC that is predictive for favorable clinical outcome in patients with metastatic HER2(+) IBC.

SUBMITTER: Anfossi S

PROVIDER: S-EPMC3885405 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer.

Anfossi Simone S Giordano Antonio A Gao Hui H Cohen Evan N EN Tin Sanda S Wu Qiong Q Garza Raul J RJ Debeb Bisrat G BG Alvarez Ricardo H RH Valero Vicente V Hortobagyi Gabriel N GN Calin George A GA Calin George A GA Ueno Naoto T NT Woodward Wendy A WA Reuben James M JM

PloS one 20140108 1

<h4>Introduction</h4>Altered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or - ...[more]

PMID: 24416156

Similar Datasets

Project description:Abstract: A subset of HER2 breast cancers with amplification of the TFAP2C gene locus becomes addicted to AP-2g. We sought to define AP-2g-regulated genes that control growth and invasiveness by comparing HER2 cell lines with differential response to TFAP2C knockdown. A set of 68 differentially expressed genes was identified, which included CDH5 and CDKN1A. Pathway analysis implicated the MAPK13/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses. The AP-2g gene signature was highly predictive of outcome in HER2-positive breast cancer patients. We conclude that AP-2g regulates a set of genes in HER2 breast cancer that drive cancer growth and invasiveness and that the AP-2g gene signature can predict outcome of patients with HER2 breast cancer. Results: Using an optimized data analysis workflow, we mapped about 50-75 million sequence reads per sample to the human genome Human Feb.2009 (GRCh37/hg19) (hg19). By RNA-seq analysis, knockdown of TFAP2C in HCC1954 with siRNA (compared to NT siRNA) identified 364 genes with significantly altered expression. To further create specificity for AP-2gamma-regulated genes, RNA-seq analysis was performed comparing expression in shHCC1954 with shTFAP2C cells vs. shNT; this analysis identified 8,986 genes with significantly altered expression. The two data sets were subsequently compared to identify a set of genes that were consistently altered with knockdown of TFAP2C by siRNA and shRNA. This comparison confirmed the identification of 152 AP-2gamma target genes in HCC1954 cells. Because HCC1954 demonstrated opposite growth regulation and invasiveness with knockdown of TFAP2C compared to SKBR3, we hypothesized that the AP-2gamma target genes responsible for growth and invasion would be differentially regulated with knockdown of TFAP2C in HCC1954 versus SKBR3. Hence, RNA-seq analysis was performed in SKBR3 after knockdown of TFAP2C with siRNA; in this analysis, a total of 3814 genes were significantly altered. The pattern of expression for the 152 AP-2gamma target genes identified in HCC1954 was subsequently compared to expression changes in SKBR3. Of note, only 79 of the 152 TFAP2C target genes in HCC1954 were found to change expression significantly in the RNA-seq data set from SKBR-3. Conclusions: Knockdown of TFAP2C with co-knockdown of CDH5 in SKBR-3 confirmed no significant effect on invasion, though there was a slight reduction in invasiveness with knockdown of CDH5 that failed to reach statistical significance (p=0.12). These findings support the conclusion that regulation of CDH5 and CDKN1A contribute to alterations of proliferation and invasiveness induced by knockdown of TFAP2C.

Dataset Information

High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer.

Introduction

Experimental design

Results

Conclusion

Publications

High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets