Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

Yi Shen,Lenora W M Loo,Harvey Risch,Dionyssios Katsaros,Emilie Marion Canuto,Brenda Y Hernandez,Lingeng Lu,Herbert Yu,Wen-Ming Chu,Clayton Chong,Nicoletta Biglia

doi:10.18632/oncotarget.3287

Abstract

LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

Highlights

Breast cancer is the most common female malignancy, annually accounting for more than a million new diagnoses worldwide [1]
In search of the Gene Expression Omnibus (GEO) database from the NCBI website, we found that a novel long intergenic non-coding RNA, LINC00472 [35] (Supplementary Figure S1), frequently appeared on top of the gene transcript lists that are associated with tumor grade or disease death in several breast cancer microarray datasets
We describe the findings of LINC00472 in our clinical study, meta-analysis and in vitro experiments

Summary

INTRODUCTION

Breast cancer is the most common female malignancy, annually accounting for more than a million new diagnoses worldwide [1]. Proteins are considered to be the major molecules carrying out essential biologic actions [8], yet only 2% of the human genome contains the codes for proteins. Most genomic sequences are understood to be transcribed, though without translation capability [9] These non-protein coding transcripts are involved in many biologic processes and cellular activities. In search of the Gene Expression Omnibus (GEO) database from the NCBI website, we found that a novel long intergenic non-coding RNA, LINC00472 [35] (Supplementary Figure S1), frequently appeared on top of the gene transcript lists that are associated with tumor grade or disease death in several breast cancer microarray datasets. We searched the literature and found no information on this lincRNA with regard to its biological functions and associations with cancer or other diseases. We describe the findings of LINC00472 in our clinical study, meta-analysis and in vitro experiments

RESULTS

DISCUSSION

MATERIALS AND METHODS