Abstract
The delayed diagnosis of pancreatic cancer has resulted in rising mortality rate and low survival rate that can be circumvented using potent theranostics biomarkers. The treatment gets complicated with delayed detection resulting in lowered 5-year relative survival rate. In our present study, we employed systems biology approach to identify central genes that play crucial roles in tumor progression. Pancreatic cancer genes collected from various databases were used to construct a statistically significant interactome with 812 genes that was further analysed thoroughly using topological parameters and functional enrichment analysis. The significant genes in the network were then identified based on the maximum degree parameter. The overall survival analysis indicated through hazard ratio [HR] and gene expression [log Fold Change] across pancreatic adenocarcinoma revealed the critical role of FN1 [HR 1.4; log2(FC) 5.748], FGA [HR 0.78; log2(FC) 1.639] FGG [HR 0.9; log2(FC) 1.597], C3 [HR 1.1; log2(FC) 2.637], and QSOX1 [HR 1.4; log2(FC) 2.371]. The functional significance of the identified hub genes signified the enrichment of integrin cell surface interactions and proteoglycan syndecan-mediated cell signaling. The differential expression, low overall survival and functional significance of FN1 gene implied its possible role in controlling metastasis in pancreatic cancer. Furthermore, alternate splice variants of FN1 gene showed 10 protein coding transcripts with conserved cell attachment site and functional domains indicating the variants’ potential role in pancreatic cancer. The strong association of the identified hub-genes can be better directed to design potential theranostics biomarkers for metastasized pancreatic tumor.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank VIT management for providing the necessary facilities to carry out this research work. The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), the Government of India agency, for the research grant. Gayathri Ashok and Megha Treesa Saju would also like to extend sincere thanks to Mr. Aniket Naha, ICMR-RA for his intellectual inputs and guidance while writing the manuscript.
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The authors gratefully acknowledge the Indian Council of Medical Research (ICMR), the Government of India agency, for the research grant (IRIS ID:2020-0690).
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SR: Conceptualization, funding acquisition, and supervision. AA: Conceptualization, methodology, and supervision. GA: Data curation, formal analysis, visualization, writing-original draft preparation SKM: Data analysis, network validation, manuscript-editing and reviewing. MTS: Data curation, data analysis of gene networks, writing-original draft.
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Ashok, G., Miryala, S.K., Saju, M.T. et al. FN1 encoding fibronectin as a pivotal signaling gene for therapeutic intervention against pancreatic cancer. Mol Genet Genomics 297, 1565–1580 (2022). https://doi.org/10.1007/s00438-022-01943-w
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DOI: https://doi.org/10.1007/s00438-022-01943-w