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An Integrated Biology Approach to Determine Metabolic Dysfunction in Retinoblastoma
Author(s) -
Guha Nilanjan,
Winer Lisa,
Babu Vishnu Suresh,
Deepak SA,
Lateef Syed,
Gundimeda Seetaraman,
Padmanabhan Arunkumar,
Dranka Brian,
Ghosh Arkasubhra
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.942.8
Subject(s) - retinoblastoma , glycolysis , oxidative phosphorylation , biology , transcriptome , metabolomics , anaerobic glycolysis , metabolic pathway , cancer research , citric acid cycle , cancer , bioinformatics , metabolism , gene , gene expression , biochemistry , genetics
Cancer cells, unlike in normal cells exhibit altered metabolic activity especially with respect to oxidative phosphorylation (OXPHOS) and glucose metabolism. In this study, we looked into the transcriptomics and metabolomics profile of retinoblastoma, a pediatric eye cancer from different sample types viz. tissue, aqueous humor, vitreous humor and tear. The samples were collected from enucleated eyes of 9 patients and 2 deceased controls, whose cause of death is not due to any eye related disease. There are 5 males and 4 female patients and comprises of both unilateral and bilateral cases. The results were also corroborated with cell line models of the cancer. Combined pathway analysis of transcriptomics data from patient tissue samples and retinoblastoma cell line WERI revealed a significant overlap in the differentially regulated genes belonging to both glycolysis and OXPHOS pathways. Similarly, combined analysis of gene expression and LC‐MS data showed many glucose metabolism genes and its corresponding metabolites to be differentially regulated in patient samples. The results also revealed decreased TCA cycle activity. To better understand the implications of these two major pathways in the progression of retinoblastoma, metabolomics study using Seahorse analyzer is in progress, which can simultaneously measure the two major energy pathways of the cell ‐ mitochondrial respiration and glycolysis ‐ in live cells, in real time. Overall the study demonstrates the utility of applying an integrative biology approach to determine the severity of metabolic dysfunction in retinoblastoma and also to identify signatures that are unique to the disease.