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Microbiota as a new indicator of colorectal cancer (CRC) heterogeneity.

Abstract : Background: Location and somatic gene signature of CRCs may impact prognosis and therapy response. The aim was to characterize colon Microbiota in CRC patients regarding location, gene markers and outcome. Methods: Patients (N = 173) signed consent for whole metagenome (shot gun sequencing on Illumina HiSeq2500) analysis of stool DNA: 72 CRC (53 sporadic-S, 19 Lynch-L), 87 asymptomatic subjects (normal colonoscopy), 14 first degree healthy relatives from Lynch families. "MOCAT" pipeline was used, library sorted (Phred quality score ¡20 Alientrimmer v0.4.0) after exclusion of < 35 nt, human genes or phage sequences. Quality sequences were aligned (REFMG.V13) and most abundant genes constructed (MBMA program v0.1). The Shaman program ( was used. The number of bacteria was estimated (REFMG program). The linear model (GLM) was implemented in the DESeq2 R kit. Dfferences between Control (N = 87) and CRCs (N = 69), between L (N = 19) and S CRCs(N = 50), and between LCRC (N = 19) and Healthy Lynch relatives were obtained after interaction of age, BMI and gender was considered (GLM model). The P < 0.1 value was retained after correction (Benjamini and Hochberg). The specific taxonomic composition of the control and CRC groups was subjected to random analysis ( Caret's R package) with two optimization parameters (precision and kappa) in the model. Results: There was no difference for gender, age (p = 0.08) and BMI (p = 0.187) in the L and S CRCs. Significant differences were observed between Normal and CRCs, C-CRC and L-CRC, L-CRC and first degree relatives based on the common component (similarity of sequences): 13 species differentiated Normal and CCRs, two were more prevalent in L-CRCs. The panels of bacteria linked with location, MSI, Ras mutations, methylation phenotypes and survival were identified. No significant link was observed with TNM Staging: I (N = 17, 2L and 15S), II (N = 12, 5L and 7S), III (N = 20, 10L, 10S), IV (N = 22.1L, 21S). DFS might be dysbiosis dependent. Conclusions: CRC dysbiosis is location-dependent. Several bacteria are associated with Ras mutation, MSI, and methylation status. They may directly or through therapies impact the prognosis. Microbiota signature should be taken in consideration in trials.
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Submitted on : Thursday, April 23, 2020 - 11:53:01 AM
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Iradj Sobhani, Amine Ghozelane, Emma Bergsten, Sean Kennedy. Microbiota as a new indicator of colorectal cancer (CRC) heterogeneity.. Journal of Clinical Oncology, American Society of Clinical Oncology, 2017, 2017 ASCO Annual Meeting I, 35 (15_suppl), pp.3615-3615. ⟨10.1200/JCO.2017.35.15_suppl.3615⟩. ⟨pasteur-02552060⟩



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