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An integrative “omics” approach, for identification of bona fides PLK1 associated biomarker in Oesophgeal adenocarcinoma

[ Vol. 19 , Issue. ]

Author(s):

Nousheen Bibi*, Sajid Rashid, Judith Nicholson, Mark Malloy, Rob O`Neill and Ted HuppPages 1-1 (1)

Abstract:


Background: The rapid expansion of genome wide profiling techniques offers the opportunity to utilize various types of information collectively in the study of human health and disease. Overexpression of Polo like kinase 1 (PLK1) is associated with oesophageal adenocarcinoma (OAC), however biological functions and molecular targets of PLK1 in OAC are still unknown.

Objectives: Here we performed integrative analysis of two “omics” data sources to reveal high level interactions of PLK1 associated with OAC.

Methods: Initially, quantitative gene expression (RPKM) was measured from transcriptomics data set of four OAC patients. In parallel alteration in phosphorylation levels was evaluated in the proteomics data set (mass spectrometry) in OAC cell line (PLK1 inhibited). Next two “omics” data sets were integrated and through comprehensive analysis possible true PLK1 targets that may serve as OAC biomarkers were assembled.

Results: Through experimental validation small ubiquitin-related modifier 1 (SUMO1) and heat shock protein beta-1 (HSPB1) were identified as novel phosphorylation targets of PLK1. Consequently in vivo, in situ and in silico experiments clearly demonstrated the interaction of PLK1 with putative novel targets (SUMO1 and HSPB1).

Conclusion: Identification of a PLK1 dependent biosignature in OAC with high confidence in two omics levels proven the robustness and efficacy of our integrative approach.

Keywords:

Omics, PLK1, SUMO1, HSPB1, kinase assay, ELISA, co-IP, PLA, insilico.

Affiliation:

Departments of Bioinformatics, Shaheed Benazir Bhutto Women University Peshawar, 2National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Department of Oncology, University of Oxford, 4Australian Proteome Analysis Facility, Macquarie University, Sydney, New South Wales 2109, Edinburgh Cancer Research Center, University of Edinburgh, Edinburgh Cancer Research Center, University of Edinburgh



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