Systematic identification of cancer-related long noncoding RNAs and aberrant alternative splicing of quintuple-negative lung adenocarcinoma through RNA-Seq. (July 2017)

• Record Type: Journal Article
• Authors: Zhang, Lu; Li, Shiyong; Choi, Yoon-La; Lee, Jinseon; Gong, Zhuolin; Liu, Xiaoqiao; Pei, Yunfei; Jiang, Awei; Ye, Mingzhi; Mao, Mao; Zhang, Xuegong; Kim, Jhingook; Chen, Ronghua
• Is Part Of: Lung cancer. Volume 109(2017)
• Page Start: 21
• Page End: 27
• Publication Date: 2017-07
• Subjects: LUAD lung adenocarcinoma -- lncRNA long noncoding RNA -- ACRG Asian Cancer Research Group -- qPCR quantitative real-time polymerase chain reaction -- BH Benjamini-Hochberg -- FDR false discover rate -- FC fold change -- A3SS alternative 3′ splice sites -- A5SS alternative 5′ splice sites -- MXE mutually exclusive exons -- RI retained intron -- SE skipped exon; Lung adenocarcinoma -- LncRNA -- Alternative splicing -- Co-expression -- Quintuple-negative; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2017.04.009
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: 243 differentially expressed lncRNAs were detected in quintuple-negative LUAD. Functions of 14 lncRNAs were predicted. We found 6 lncRNA-nearby mRNA co-expressed pairs associated with lung development. Two most frequent aberrant splicing events were found in MYH14 and ESYT2 . Occurrence of MET exon 14 skipping were reported in quintuple-negative LUAD. Abstract: Objectives: Lung adenocarcinoma (LUAD) is a common subtype of non-small cell lung cancer prevalent in Asia. There is a dearth of understanding regarding the transcriptome landscape of LUAD without primary known driver mutations. In this study, LUAD samples without well-known driver mutations occurring in EGFR, KRAS, ALK, ROS1 or RET (quintuple-negative) were used for transcriptome study with a focus on long noncoding RNAs (lncRNAs), alternative splicing and gene fusions. Materials and methods: 24 pairs of LUAD and adjacent normal samples and 13 tumor-only samples derived from 37 quintuple-negative patients were used. Differentially expressed lncRNA transcripts were detected by paired t -test and were validated by qPCR. Functions of lncRNAs were predicted by co-expressed mRNAs. Aberrant splicing events in LUAD were identified using MISO. In addition, gene fusions were screened by SOAPfuse. Results and conclusion: In total, 90 and 153 up- or down-regulated lncRNA transcripts were detected in LUAD samples in comparison with the adjacent normal samples. The most significantly differentially expressed lncRNA transcript was ENST00000598996.1 ( FENDRR ) down-regulated in LUAD. By lncRNA-mRNA co-expression analysis, functions of 14 lncRNAs were predicted. The predicted functions included vasculature development, immune response, cell cycle and respiratory gaseous exchange. Furthermore, six co-expressed pairs of lncRNAs and their nearby protein coding genes were identified as associated with lung development. This study also identified two highly recurrent (22 in 24) differential exon skipping events occurring in MYH14 and ESYT2 with exon including isoforms of both genes up-regulated in isoform percentage in LUAD samples. On the other hand, two out of 24 LUAD samples possessed the driver mutation exon 14 skipping of MET . The transcriptional alterations of LUAD samples without well-known driver mutations identified in the study can be used as references for future research. The translational values of these transcriptional changes are also worthy of further investigation.