Expression and network analysis of YBX1 interactors for identification of new drug targets in lung adenocarcinoma

Abstract

Y-Box Binding protein 1 (YBX-1) is known to be involved in various types of cancers. It's interactors also play major role in various cellular functions. Present work aimed to study the expression profile of the YBX-1 interactors during lung adenocarcinoma (LUAD). The differential expression analysis involved 57 genes from 95 lung adenocarcinoma samples, construction of gene network and topology analysis. A Total of 43 genes were found to be differentially expressed from which 17 genes were found to be down regulated and 26 genes were up-regulated. We observed that Polyadenylate-binding protein 1 (PABPC1), a protein involved in YBX1 translation, is highly correlated with YBX1. The interaction network analysis for a differentially expressed non-coding RNA Growth Arrest Specific 5 (GAS5) suggests that two proteins namely, Growth Arrest Specific 2 (GAS2) and Peripheral myelin protein 22 (PMP22) are potentially involved in LUAD progression. The network analysis and differential expression suggests that Collagen type 1 alpha 2 (COL1A2) can be potential biomarker and target for LUAD.

Keywords: RNA-Seq.; YBX1; lung adenocarcinoma; regulatory network.

Figure 1

Quality of the samples after filtering. (1A) Heatmap shows the unsupervised hierarchical clustering of the normal and tumor samples in LUAD after filtration. The row represents the genes and column represent the samples. Normal and tumor samples are clustered within their group based on their Euclidean distance. (1B) Principle Component Analysis for the filtered samples shows that first principle component (PC1) separates the normal and tumor samples. In both analysis, samples are found to be grouped within their type.

Figure 1

Quality of the samples after filtering. (1A) Heatmap shows the unsupervised hierarchical clustering of the normal and tumor samples in LUAD after filtration. The row represents the genes and column represent the samples. Normal and tumor samples are clustered within their group based on their Euclidean distance. (1B) Principle Component Analysis for the filtered samples shows that first principle component (PC1) separates the normal and tumor samples. In both analysis, samples are found to be grouped within their type.

Figure 2

Correlation plot between the differentially expressed genes in LUAD. Correlation with the significance p- value (<0.05) are shown. Insignificant correlation are left blank without colors.

Figure 3

Gene network constructed and analyzed with Cytoscape. Directed root network built from the gene interaction data obtained from GeneMANIA. Network has 86 nodes with 3611 interactions. Figure 3A, 3B and 3C highlights the top 10 genes with closeness centrality, betweenness centrality and degree respectively. CDKN1A is the common gene between closeness centrality and betweenness centrality. Five genes namely, HLA-DRA, HLA-A, HLA-DRB1, HLA-DMB and B2M showed highest betweenness centrality and degree.

Figure 3

Gene network constructed and analyzed with Cytoscape. Directed root network built from the gene interaction data obtained from GeneMANIA. Network has 86 nodes with 3611 interactions. Figure 3A, 3B and 3C highlights the top 10 genes with closeness centrality, betweenness centrality and degree respectively. CDKN1A is the common gene between closeness centrality and betweenness centrality. Five genes namely, HLA-DRA, HLA-A, HLA-DRB1, HLA-DMB and B2M showed highest betweenness centrality and degree.

Figure 3

Gene network constructed and analyzed with Cytoscape. Directed root network built from the gene interaction data obtained from GeneMANIA. Network has 86 nodes with 3611 interactions. Figure 3A, 3B and 3C highlights the top 10 genes with closeness centrality, betweenness centrality and degree respectively. CDKN1A is the common gene between closeness centrality and betweenness centrality. Five genes namely, HLA-DRA, HLA-A, HLA-DRB1, HLA-DMB and B2M showed highest betweenness centrality and degree.

Figure 4

Interactors of GAS5 derived from RAIN database. Interaction with confidence level > 0.7 is considered as significant. Among the interactors GAS2 and PMP22 are the proteins involved in interaction with GAS5.