Identification of KCNJ5 gene an adverse prognosis associated novel onco-ionchannel in Indian pancreatic cancer cohort

Figures

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  Fig. 1. Pathway associated landscape evaluation: Differentially methylated 91 gene signature status evaluation through A epigenoics roadmap project, B KEGG 2021 Human, C proteomic signature through Reactome 2022, D CHEA3 gene signature density-based heat map density mapping transcription factor, E IPA pathway analysis showing respective interactions. Orange annotation: significant, blue annotation: non-significant

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  Fig. 2. Clinical relevance of significant differentially methylated genes. Differential expression (TCGA, tumor Vs GTEx, normal) of A KCNJ5 B RASA3 C CLIC5. Differential methylation pattern of KCNJ5 (D), CACNB2 (E) (TCGA, tumor Vs TCGA, normal) using Wilcoxon Raksum test; p = 0.037. F Kcnj5 protein expression was evaluated in CPTAC patient samples (tumor vs normal). Overall survival shown through Kaplan Meyer plot across TCGA patient samples post splitting the samples in low and high risk groups for G CACNB2, p = 4e-04, (H) KCNJ5, p = 0.97. I Differential expression of KCNJ5 on PDAC paired tumor samples (n = 20, p < 0.026). J Overall survival using Kaplan Meier survival analysis of KCNJ5 using gene expression data done on 20 patient samples in Indian cohort (1 = high KCNJ5 group, 2 = low KCNJ5 group). Time is measured in days. K KM done between the alcohol and non-alcoholic groups and was found to be border line significant (p < 0.07)

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  Fig. 3. Deconvolution immune profiling using LM22 for A KCNJ5, B CACNB2 expression correlation in different immune cells. Correlation coefficient is denoted by blue to red. Blue denoting negative correlation, red denoting positive correlation. Expression of KCNJ5 in Human Protein Atlas C. Whisker plot comparing the RNA expression (in nTPM) of KCNJ5 in 328 GTEX normal pancreatic tissue samples and 46 pancreatic cancer cell lines D. Immunohistochemistry of KCNJ5 in normal pancreatic tissue

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  Fig. 4. Functional validation of KCNJ5 gene. Gene Ontology based on A biological processes using STRING B molecular functions C cellular components. (D) Interaction between all ion channel genes, including KCNJ5, CACNB2, KCNA3, KCNA6, GABBR2

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  Fig. 5. Functional enrichment of KCNJ5: A Volcanic graph of KCNJ5 representing positive (red) and negative (green) correlated genes. B Heatmap of KCNJ5 associated positive correlated genes. C Heatmap of KCNJ5 associated negative correlated genes. D Functional and pathways enrichment analysis of KCNJ5 associated positive (blue) and negative (yellow) correlated genes. E Enrichment plot for ribosome associated pathways. F Enrichment plot for hematopoietic cell lineage pathways

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  Fig. 6. Identification, functional enrichment and cluster analysis of protein–protein interaction network of DEICGs in PDAC. A Heat map depicting the average gene expression (log2FC)of 129 DEICGs in three datasets -GSE211398, GSE93326 and TCGA. B Functional enrichment network of DEICGs that is cluster ID-colored, with nodes with the same cluster ID being closer to one another C. Bar plot of Top 20 significant GO Biological Processes and KEGG pathways of DEICGs D.MCODE clusters identified in the network of protein–protein interactions of DEICGs

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  Fig. 7. Molecular docking study of protodioscin to the modelled Kcnj5 protein. A 3D diagram of the complex. B 2D diagram of interactions of the ligand with the amino acid residues at the binding site. C–E Mapping of binding site cavity according to the presence of H-bond donor–acceptor residue, hydrophobicity, and ionizability, respectively