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Med | Multi-omics accedere ad tabularum integrated tumore, immunes et microbial landscape de coloreectal cancer revelat in commercio de microbiome cum immune ratio
Licet biomarkers ad primaria colonia cancer fuisse studied extensive in annis, current orci guidelines confidunt solum in Tumor-lymphatch node-metastasis (MMR), aut in microsatellite instabilitatem (MSI) ad determinare curatio. Inquisitores attendendum est defectum consociationis inter gene expressio-fundatur immune respondeo, microbial profiles, et tumore Stroma in Cancro genome Atlas (TCGA) Colorectal Cohors et patientes estote et superesset.
Ut research progressed, quantitatis primaria coloreectal cancer, inter cancer cellular, immune, stromal, aut microbial naturam de cancer, sunt relata ad significantly intelligere, quam eorum interactiones afficit afficiens.
Dissecimus necessitudinem inter phenotypic multiplicitate et exitus, a quadrigis ex investigatores a Sidra Institutum Medical Research in Qatar nuper developed et convalided in combining microbiome characteres et immune rejectio constantibus (ICR). In quadrigis perfecerunt comprehensive genomic analysis de nova gelida exempla ex CCCXLVIII aegris cum primaria coloreectal cancer, inter RNA sequencing de anses et matched sanus, cellula, totius exoma, in micromome. In studio erat published in natura medicina ut "integrari tumore, immune et microbiome atlas de colonia cancer."
Articuli published in natura medicina
AC-Ican Overview
Inquisitores usus est an orthogonal genomic suggestus ad analyze recens gelida tumor exemplaria et matched adjacent sanus colonia TEXTUS (tumor-normalis pairs) ex aegris cum a histologic diagnosis de colonia cancer sine systemic Lorem. Ex toto-exome sequencing (Wes), RNA, seq data qualis imperium, et inclusion criteria protegendo, genomic notitia ex CCCXLVIII aegris sequatur et propter downstream analysis cum mediani sequi et propter downstream analysis cum mediani sequi et usus est ad downstream analysis cum mediani sequuntur, et usus est ad downstream analysis cum mediani sequuntur-4.6 annis. Et investigationis quadrigis nomine hoc resource Sidra-Lumc AC-Ic, A Map et Rector ut immune, cancer-microbiome interactions (figure I).
Molecular Ordo per icr
Captantium modularis paro of immune geneticae markers ad continuum cancer immunosurveilnce, vocavit ad immune constans rejectionem (icr), in investigationis quadrigis optimized in icr diversis cancer est in XX-gene panel, vesica cancer eam in pectus et cancer. ICR etiam consociata cum immunotherapy responsum in varietate cancer types, comprehendo pectus cancer.
Primo, in investigatores convalescit in ICR signature de AC-Icam cohortis, usura an ICR gene-secundum cooperatores genus accedere ad referatur cohortis in tria clusters / immune subyps, Medium icr et humilis ICR (Frigus Pylade), Medium ICR et humilis (frigus anorum), Medium ICR et humilis ICR (Frigus Penes) (Figura 1b). Inquisitores propria est immune propensionem consociata cum consensu Molecular subyps (CMS), A transcriptome-fundatur genus colon cancer. Et CMS genera includitur CMS1 / immune, CMS2 / Canonica, CMS3 / Metabolicae et CMS4 / Mesenchymal. Analysis ostendit quod ICR scores fuerunt negative connectuntur cum certa cancer cellula semitis in omnibus CMS Subtypes, positivum correlationibus immunosuppressive et stromal actis trucidabunt in immunosuppressive et stromal actis actores sunt solum in Cms4 tumores.
In omnibus cms, abundantia naturalis interfectorem (NK) cellula et T cellula subterets erat summum in ICR alias leukocyte subyps et aliter in altum in altum (figuram in Colorectal Cancer Prognore (Figura in Colorectal Cancer.
Figura I. AC-Icam studium consilio, immune, related gene signature, immune et mocecular subtypes et salvos.
ICR captures tumor-ditatus, clonally amplificari T cellulis
Tantum a minoritate T cells TELLIBRIBILLATRING Tumor TEXTUS sunt relatum esse propria ad tumorem antigens (minus quam X%). Ideo maior pars intra-tumor T cellulis referred to as quod byStander T cellulis (byStander T cellulis). Et fortissimum correlatione cum numerus conventional T cellulis cum productive TCRs est observatum in stromal cellula et leukocyte subpopulations (deprehenditur a RNA, seq), quod potest estimate T cellula subpopulations (Figure 2a). In ICR clusters (altiore et CMS classificationem), summa clonality immunes seq TCRs dictum est in ICR-excelsum et CMS Subype CMS1 / immune coetus (Figure 2c), cum summa proportio ICR-alto anses. Using toto transcriptome (18,270 genes), sex ICR genes (IFNG, Stat1, IRF1, CCL5, Gzma positive consociata cum TRCE TRANS Clonality (Figura 2D). Immunoseq TCR Clonality connectuntur magis fortiter cum maxime ICR genes quam correlations observata usura tumore-responsive CD8 + venalicium (Figura 2f et 2f). In conclusione, quod superius analysis suggerit, quod ICR signature captura coram tumore-ditatus, clonally amplificari T cellulis et explicare suam prognostic implicationes.
Figura II. TRT metrics et correlatione cum immunes actis genes, immunes et mocecular subyps.
Microbiome compositionem in sanus et colonia cancer texturis
In investigatores peragendos 16s RRNA sequencing usura DNA extrahitur ex matched tumore et sanus colonia TEXTUS ex CCXLVI aegris (instar 3a). Nam sanatio, in investigatores insuper resolvitur 16s rrna gene sequencing notitia ex an additional XLII tumor exemplaria, quae non sunt matched normalis DNA available for analysis. Primo, inquisitores comparari relative de Flora inter matched tumores et sanus colonia TEXTUS. Clostridium perfringens erat significantly auctus in tumores comparari ad sanus samples (instar 3a-3D). Non fuit significant differentia alpha diversitas (diversitas et abundantia speciei in una sample) inter tumore et sanus exemplaria, et modico reductionem in microbial diversitas observatur in ICR-alto tumores ad ICR-humilis.
Ad deprehendere clinically relevant consociationes inter microbial profiles et orci eventus, inquisitores intendebant ad usum 16s RRNA genom sequencing notitia ad identify microbiome features quod praedictum salvos. In AC-Icam246, in Inquisitores cucurrit an OS COX procedere exemplar quod lectus XLI features cum non-nulla coefficientes (consociata cum differentialis mortalitate periculo), dicitur MBR classifiers (Figura 3f vocavit MBR (Figura 3F).
In hoc disciplina cohort (Icam246), a low mbr score (MBR <0, humilis MBR) fuit consociata cum significantly minus periculo mortis (LXXXV%). Inquisitores confirmata in consociatione inter humilis MBR (periculum) et diuturna OS in duo independently convalescit cohortibus (Icga et tcga-coad). (Figura III) De studiis ostendit fortis per correlationem inter endogastric cocci et MBR scores, quae erant similes in tumore et sanus colonia TEXTUS.
Figura III. Microbiome in tumore et sanus textuum et necessitudinem cum ICR et patientes estote superessendam.
Conclusio
Multi-omics accedere in hoc studium dat penitus deprehendatur et analysis de mocecular signature de immune responsio in Colorectal Cancer et reveals in commercium inter microbiome et immune ratio. Altum TCT sequencing de tumore et sanus textuum revelata quod prognostica effectus ICR potest esse debitum ad facultatem capere tumor-ditatus et tumore antigen-specifica T cellula clones.
Per analyzing tumore microbiome compositionem usura 16s rrna gene sequencing in AC-Icam exempla, in quadrigis identified a microbiome signature (MBR periculo score) fortis prognostica valorem. Licet haec signature ex tumore exempla, erat fortis correlationem inter sanus colorecta et tumore MBR periculo score, suggerendo quod hoc signature capere ventrem microbiome compositionem aegris. Per combining in ICR et MBR ustulo, quod est possibile ut identify et convalidandum a multi-omic studiosum Biomarker quod predicts superessendam in aegris cum colonia cancer. In studium est Multi-omic Dataset praebet a resource ad melius intelligere colonia cancer biology et auxilium invenire personalized therapeutica accedit.
Post tempus: Iun, 15-2023
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