Survival analysis and functional annotation of long non-coding RNAs in lung adenocarcinoma

Abstract

Long non-coding RNAs (lncRNAs) are a subclass of non-protein coding transcripts that are involved in several regulatory processes and are considered as potential biomarkers for almost all cancer types. This study aims to investigate the prognostic value of lncRNAs for lung adenocarcinoma (LUAD), the most prevalent subtype of lung cancer. To this end, the processed data of The Cancer Genome Atlas LUAD were retrieved from GEPIA and circlncRNAnet databases, matched with each other and integrated with the analysis results of a non-small cell lung cancer plasma RNA-Seq study. Then, the data were filtered in order to separate the differentially expressed lncRNAs that have a prognostic value for LUAD. Finally, the selected lncRNAs were functionally annotated using a bioinformatic and systems biology approach. Accordingly, we identified 19 lncRNAs as the novel LUAD prognostic lncRNAs. Also, based on our results, all 19 lncRNAs might be involved in lung cancer-related biological processes. Overall, we suggested several novel biomarkers and drug targets which could help early diagnosis, prognosis and treatment of LUAD patients.

Keywords: bioinformatics; functional annotation; lung adenocarcinoma; prognostic lncRNAs; systems biology.

Figure 1

Schematic outline of the research protocol

Figure 2

Association of lncRNAs with OS in LUAD. The association of (A) ADAMTS9‐AS2, (B) C8orf34‐AS1, (C) CADM3‐AS1, (D) FAM83A‐AS1, (E) FENDRR, (F) LANCL1‐AS1, (G) LINC00092, (H) LINC00467, (I) LINC00857, (J) LINC00891, (K) LINC00968, (L) LINC00987, (M) LINC01506, (N) MAFG‐AS1, (O) MIR497HG, (P) RHOXF1‐AS1, (Q) TBX5‐AS1, (R) SNHG6, lncRNAs with the OS of LUAD patients. TPM is a unit of transcript expression and the abbreviation of Transcripts per Million. The plots were achieved using GEPIA web server

Figure 3

Altered expression of 19 LAProLncRs. The altered expression of (A) ADAMTS9‐AS2, (B) C8orf34‐AS1, (C) CADM3‐AS1, (D) FAM83A‐AS1, (E) FENDRR, (F) LANCL1‐AS1, (G) LINC00092, (H) LINC00467, (I) LINC00857, (J) LINC00891, (K) LINC00968, (L) LINC00987, (M) LINC01506, (N) MAFG‐AS1, (O) MIR497HG, (P) RAMP2‐AS1, (Q) RHOXF1‐AS1, (R) SNHG6, (S) TBX5‐AS1, lncRNAs in LUAD tumour samples. FC and TPM are the abbreviations of Fold‐Change and Transcripts per Million respectively. Box plots were achieved using GEPIA web server

Figure 4

Gene coexpression networks. (A). The network of LAProLncRs and their DECEGs; the yellow nodes represent LAProLncRs. (B) The gene coexpression network of LAProLncRs. The intensity of violet node colour is proportional to betweenness centrality score; stronger violet colour indicates higher betweenness centrality score. Red and Blue node borders are indicative of overexpression and underexpression respectively. The width of node border indicates the GEPIA Log2FC; wider border indicates greater Log2FC. The size of violet nodes and their label font size indicate the node degree; bigger violet node and label font size are indicative of higher node degree. The edge colour and width shows the GEPIA PCC; darker and wider edge is indicative of higher GEPIA PCC. PCC is the abbreviation of Pearson Correlation Coefficient. The networks were reconstructed using the Cytoscape software

Figure 5

The lncRNA‐GO‐BP association network. The yellow nodes represent LAProLncRs. The intensity of pink node colour indicates the betweenness centrality score; stronger pink colour indicates higher betweenness centrality score. The node height is proportional to node degree; Bigger node indicates higher node degree. The edge colour is representative of the source database of predicted GO term and the reference tissue type. Please refer to Table 2 for finding the description of GO IDs. The network was reconstructed using the Cytoscape software

Figure 6

The expression‐stage plot of LAProLncRs. (A) The expression‐stage plot of ADAMTS9‐AS2 lncRNA. (B) The expression‐stage plot of FAM83A‐AS1 lncRNA. (C) The expression‐stage plot of LANCL1‐AS1 lncRNA. (D) The expression‐stage plot of LINC00092 lncRNA. (E) The expression‐stage plot of LINC00857 lncRNA. (F) The expression‐stage plot of LINC00891 lncRNA. (G) The expression‐stage plot of MIR497HG lncRNA. (H) The expression‐stage plot of SNHG6 lncRNA. (I) The expression‐stage plot of TBX5‐AS1 lncRNA. The plots were achieved by the GEPIA web server

Figure 7

The impact of smoking habit and gender on the expression of LAProLncRs. (A) The impact of smoking habit on ADAMTS9‐AS2 expression in LUAD. (B) The impact of smoking habit on FAM83A‐AS1 expression in LUAD. (C) The impact of smoking habit on MAFG‐AS1 expression in LUAD. (D) The impact of smoking habit on SNHG6 expression in LUAD. (E) The impact of gender on LINC00092 expression in LUAD. (F) The impact of gender on SNHG6 expression in LUAD. (G) The impact of gender on LINK00467 expression in LUAD. The plots were obtained from the Lung Cancer Explorer