PT  - JOURNAL ARTICLE
AU  - Arunagiri Kuha Deva Magendhra Rao
AU  - Krishna Patel
AU  - Sunitha Korivi Jyothi
AU  - Balaiah Meenakumari
AU  - Shirley Sundersingh
AU  - Velusami Sridevi
AU  - Thangarajan Rajkumar
AU  - Akhilesh Pandey
AU  - Aditi Chatterjee
AU  - Harsha Gowda
AU  - Samson Mani
TI  - Identification of lncRNAs associated with early stage breast cancer and their prognostic implications
AID  - 10.1101/543397
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 543397
4099  - http://biorxiv.org/content/early/2019/02/15/543397.short
4100  - http://biorxiv.org/content/early/2019/02/15/543397.full
AB  - Breast cancer is a common malignancy among women with the highest incidence rate worldwide. Dysregulation of long non-coding RNAs occurring in the preliminary stages of breast carcinogenesis is poorly understood. In this study, RNA sequencing was done to identify long non-coding RNA expression profiles associated with early-stage breast cancer. RNA sequencing was done in 6 invasive ductal carcinoma (IDC) tissues along with paired normal tissue samples, 7 ductal carcinoma in situ (DCIS) tissues and 5 apparently normal breast tissues. We identified 375 differentially expressed lncRNAs (DElncRNAs) in IDC tissues compared to paired normal tissues. Antisense transcripts (∼58%) were the largest subtype among DElncRNAs. About 20% of the 375 DElncRNAs were supported by typical split readings leveraging their detection confidence. Validation was done in n=52 IDC and paired normal tissue by qRT-PCR for the identified targets (ADAMTS9-AS2, EPB41L4A-AS1, WDFY3-AS2, RP11-295M3.4, RP11-161M6.2, RP11-490M8.1, CTB-92J24.3 and FAM83H-AS)1. We evaluated the prognostic significance of DElncRNAs based on TCGA datasets and overexpression of FAM83H-AS1 was associated with patient poor survival. We confirmed that the down-regulation of ADAMTS9-AS2 in breast cancer was due to promoter hypermethylation through in-vitro silencing experiments and pyrosequencing.AbbreviationsDCISductal carcinoma in situIDCinvasive ductal carcinomaNGSNext generation sequencinglncRNAlong non-coding RNAslincRNAlong intergenic non-coding RNATNBCTriple negative breast cancersBHBonferroni and Benjamini–HochbergPCAPrincipal component analysisPCCPearson’s correlation coefficientPCGProtein coding genes