Implementation of a bioinformatics pipeline for exploring the intratumoral microbiome and deciphering the heterogeneity of human hepatocellular carcinoma


Abstract

Thomas Gkekas / Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou
Campus, Greece, Athens, Greece / G.P. Livanos and M. Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Medical School, National and Kapodistrian University of Athens, 3 Ploutarchou Str., Athens, Greece
Dionisios Dimitreas / Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens, Greece
Panagiotis Agioutantis / Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Greece, Athens, Greece / G.P. Livanos and M. Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services,
Evangelismos Hospital, Medical School, National and Kapodistrian University of Athens, 3 Ploutarchou Str., Athens, Greece
Diomi Mamma / Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens, Greece
Fragkiskos Kolisis / Biotechnology Laboratory, School of Chemical Engineering, National Technical University of Athens, 5 Iroon Polytechniou Str., Zografou Campus, Athens, Greece
Heleni Loutrari / G.P. Livanos and M. Simou Laboratories, First Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Medical School, National and Kapodistrian University of Athens, 3 Ploutarchou Str., Athens, Greece

Topic: Biocatalysis and Molecular Medicine

The existence of intratumoral microbiota has been recently recognized, however, its relevance to hepatocellular carcinoma (HCC) diversity remains unclear. Herein, a bioinformatics pipeline is implemented to uncover in parallel the host-tumor transcriptome and microbiome profiles, through mining of available RNA-seq data from HCC and matched adjacent normal tissues. Single-sample gene-set enrichment analysis using liver-specific gene sets divided HCC samples into poorly and well-differentiated molecular subtypes. Comparison of microbiome taxonomy, diversity and function revealed significant dissimilarities in HCC versus normal controls as well as between HCC subtypes. Integration of transcriptome and microbiome data highlighted Bacillus thuringiensis, Delftia lacustris and Hepatitis B virus as potential modulators of crucial cancer hallmarks and liver-specific gene signatures. These results shed light into the intratumoral microbiome and its potential association to HCC heterogeneity.


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