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INat Med | Indlela yokuthola imiyalezo eminingi yokuthola isimila esihlanganisiwe, isimo somdlavuza we-music kanye nomdlavuza wemibala wembula ukuxhumana kwe-microbiome ngamasosha omzimba
Yize ama-biomarker womdlavuza wamakholoni aphambili afundwa kakhulu eminyakeni yamuva, izinkombandlela zamanje zemitholampilo zincike kuphela kwi-Tumor-Metastasis Staging kanye nokutholwa kokuqina kwe-DNA Mismatch (MMR) (ngaphezu kokuhlolwa kwe-pathology evamile) ukuthola izincomo zokwelashwa. Abaphenyi baphawule ukuntuleka kokuhlangana kwezimpendulo zomzimba ezivezwa zofuzo, amaphrofayli ama-microbial, kanye ne-rugroma yomdlavuza ku-Cancer Genome Atlas (TCGA) umdlavuza womdlavuza womdlavuza we-atlas (TCGA).
Njengoba ucwaningo seluthuthukile, izici zobuningi bomdlavuza wezemibalali oyinhloko, kufaka phakathi umdlavuza weselula, umngcele, noma uhlobo lwe-microbaal lomdlavuza, kodwa kubikwa ukuthi kulinganiselwe okulinganiselwe ngemiphumela yawo emtholampilo, kepha kusakuqonda ukuthi ukusebenzisana kwabo kuthinta kanjani imiphumela yeziguli.
Ukusihlukanisa nobudlelwano phakathi kobumbano obuhle kanye nomphumela, iqembu labaphenyi abavela eSidra Institute of Medical Research eQatar basanda kuthuthukiswa futhi baqinisekisa iqembu leziguli ezinezimpawu ezinhle zokuhlanganisa izici ze-microbiome kanye nokuvuka kwekwenqatshwa (i-ICR). Iqembu lenze ukuhlaziya okugcwele kwezolona amasampula amasha aqandisiwe kusuka ezigulini ezingama-348 anomdlavuza wama-colouteal, afaka ukulandelana kwe-rna, okuhambisana nokulandelana kwe-rna gerome genome ukuze uqhubeke nge-microbiome. Lolu cwaningo lushicilelwe emvelweni umuthi "njenge-turobe ehlanganisiwe, imisindo kanye ne-microbiome atlas yomdlavuza wekoloni".
I-athikili eshicilelwe emvelweni umuthi
Ukubuka konke kwe-AC-ICAM
Abaphenyi basebenzise ipulatifomu ye-Orthogonal Genomic yokuhlaziya amasampula amasha e-Tumor anempilo futhi afaniswe nezicubu zekholoni ezinempilo ezisondelene (ama-tumor-ad aurs) ezigulini ezinokuxilongwa komdlavuza wekoloni ngaphandle kokwelashwa okuhle. Ngokusekelwe ekulandelweni kwekhwalithi okuphelele kwekhwalithi ebekiwe, i-RNA-SEQ Ikhwalithi yekhwalithi, kanye nokuhlolwa kwenqubo yokufaka, idatha ye-genomic kusuka ezigulini ezingama-348 igcinwe futhi isetshenziselwe ukuhlaziya okwehla ngomkhumbi ngeminyaka eyi-4,6. Iqembu lokucwaninga liqamba leli nsiza selida-lumc ac-iCAM
Ukuhlukaniswa kwama-molecular kusetshenziswa i-ICR
Ukuthwebula isethi yama-moduner yezimpawu zofuzo zomzimba ngokuqhubeka komdlavuna, okubizwa ngokuthi ama-immune ekwenqatshelwe (i-ICR), iqembu lokucwaninga lakha i-ICR ngokulivumelanisa nephaneli yomdlavuza ohlukile, kufaka phakathi umdlavuza webele, kanye nomdlavuza webele. I-ICR nayo ihlanganiswe nempendulo ye-immunotherapapy ezinhlotsheni ezahlukahlukene zomdlavuza, kufaka phakathi umdlavuza webele.
Okokuqala, abacwaningi baqinisekisa isiginesha ye-ICR ye-AC-ICAM COHORT, besebenzisa indlela yokuhlanza abasezingeni le-ICR ukuhlukanisa i-cohort kuma-cohort amathathu kuma-ICRTICE Abaphenyi babonakalisa ubuntu bokuzivikela obuhambisana nama-subtypes ama-molecular ahlukahlukene (CMS), ukuhlukaniswa komdlavuza osuselwa kwabadlulisiwe komdlavuza wekoloni. Izigaba ze-CMS zifaka i-CMS1 / Immune, i-CMS2 / Canonical, CMS3 / Metabolic ne-CMS4 / MESETHMY. Analysis showed that ICR scores were negatively correlated with certain cancer cell pathways in all CMS subtypes, and positive correlations with immunosuppressive and stromal-related pathways were observed only in CMS4 tumors.
Kuwo wonke ama-CMS, ubuningi beseli lezembatho yemvelo (nk) ama-subsets weseli we-t cell aphezulu kakhulu e-Icr High ama-bustets, ahlukahlukene ama-aukocyte ahlukahlukene ane-ICR ephakeme (isithombe 1d), iqinisekisa iqhaza le-ICROSTIC yomdlavuza we-ICR.
Isibalo
I-ICR ithumba i-Tumor-ethuthukisiwe, ye-T Collally Amplified T cell
Imbalwa kuphela lamaseli we-T angena ngaphakathi kwezicubu zomculo abikiwe ukuthi acaciswe ukuthi acaciswe ama-antigns we-tumor antigns (ngaphansi kuka-10%). Ngakho-ke, iningi lamaseli we-Intra-Tumor T abizwa ngokuthi amaseli we-bystander T (Bystander T). Ukuhlobana okunamandla kakhulu nenani lamaseli we-T ajwayelekile ane-TCCS akhiqizwayo kubhekwe endaweni eyi-Stromal cell kanye ne-leukocyte subpopations (kutholwe yi-RNA-SEQ), engasetshenziswa ukulinganisa ama-subpopations we-T Cell (Umdwebo we-2A). Ezihlukanisweni ze-ICR (ukuhlukaniswa okuphelele kanye ne-CMS), kubhekwe ubuhlakani obukhulu bokuzivikela emzimbeni we-SEQ kanye ne-CMS subtype CMS1 / ama-Immbvice Butterpe Usebenzisa lonke i-transcriptipmeme (izinhlobo zofuzo eziyi-18,270), izinhlobo eziyisithupha ze-ICR (IFNG, Stat1, i-IRF1, i-CXC1, i-GZMA, kanye ne-CXCL10) zaziphakathi kwe-TCR immune Seq Clonity (Umdwebo 2D). I-Immunoseq TCClity CRCALITIAL ixhumeke kakhulu ngohlobo lwe-ICR iningi ukwedlula ukuxhumana okubonakalayo kusetshenziswa amamaki aphendulayo e-CD8 + (Umdwebo we-2F ne-2F). Ekuphetheni, lokhu kuhlaziywa okungenhla kusikisela ukuthi isiginesha ye-ICR ithumba ubukhona bamaseli athuthukiswe-isimila, akhuphuke kakhulu we-T futhi angachaza imiphumela yawo ye-pregnostic.
Umdwebo 2. Amametri ka-TR
Ukwakheka kwe-Microbiome ngezicubu ezinempilo nezekholoni
Abaphenyi benze ukulandelana kwe-16s RRNA Kusetshenziswa i-DNA kukhishwe kusuka ku-tumor efanisiwe kanye nezicubu zekoloni ezinempilo ezivela ezigulini ezingama-246 (Umdwebo 3a). Ngokuqinisekiswa, abacwaningi baphinde bahlaziywa kabusha i-16S GRNA Gene Requencing idatha kusuka kumasampula angeziwe angama-42 angenawo ama-DNA ajwayelekile atholakalayo ukuze ahlaziywe. Okokuqala, abacwaningi baqhathanisa ubuningi beFlora obuningi phakathi kwamathumbu afanisiwe nezicubu zekoloni ezinempilo. I-Closerdium Phroprisens yayikhuphuka kakhulu emathuneni iqhathaniswa namasampula anempilo (Umdwebo 3A-3D). Kwakungekho mehluko omkhulu ku-Alpha Diversity (ukwehlukahlukana kanye nobuningi bezinhlobo zesampula eyodwa) phakathi kwesimila namasampula anempilo, kanye nokwehliswa okunesizotha, ukuncishiswa okunesizotha kubhekwe kuma-tumors aphezulu we-ICR.
Ukuthola izinhlangano ezifanelekile emtholampilo phakathi kwamaphrofayili we-microbial kanye nemiphumela yemitholampilo, abacwaningi bahlose ukusebenzisa idatha yohlobo lwe-RRNA gene ukuthola imininingwane yokuthola ama-microbiome abikezela ukusinda. E-AC-iCAM246, abacwaningi bagijimisa imodeli ye-OS REX Regression ekhethe izici ezingama-41 ezinama-coefficients angewona ama-zero (ezihambisana nengozi yokufa okuhlukile), ebizwa nge-MBR Criseifiers (Umdwebo 3f).
Kulesi cohort cohort (iCam246), i-MBR Score ephansi (MBR <0, i-MBR ephansi) yayihlotshaniswa nengozi ephansi kakhulu yokufa (85%). Abaphenyi bakuqinisekisile inhlangano phakathi kwe-MBR ephansi (ubungozi) kanye ne-OS ende e-OS efinyeleleka ama-cohorts amabili aqinisekisiwe (iCam42 ne-TCGA-CoAD). .
Umdwebo 3. I-Microbiome ngesimila kanye nezicubu ezinempilo nobudlelwano ne-ICR nokusinda kwesiguli.
Ukugcina
Indlela ye-Multi-Omics esetshenzisiwe kulolu cwaningo inika amandla ukutholwa okuphelele nokuhlaziywa kwesiginesha ye-molecular yokuphendula komzimba emdlavuzweni we-colobieclial futhi iveze ukuxhumana phakathi kwe-microbiome namasosha omzimba. Ukulandelana okujulile kwe-TRCR kanye nezicubu ezinempilo kuveze ukuthi umphumela we-ICORTONESTIC we-ICR angabangelwa yikhono lawo lokufaka ama-cloones acacisiwe acaciswe
Ngokuhlaziya i-tumob microbiome ukwakheka usebenzisa i-16s rrna gene gene amasampula e-AC-ICAM, iqembu liveze isiginesha ye-microbiome (i-MBR ingozi amaphuzu) ngenani eliqinile le-prognostic. Yize lesi siginesha sithathwe kumasampula emihlanga, kwaba nokuhlangana okuqinile phakathi kwe-colorectum enempilo ye-aleorectum kanye ne-tumor mbr Score, ephakamisa ukuthi lesi siginesha singathatha ukwakheka kwe-microbiomet. Ngokuhlanganisa izikolo ze-ICR ne-MBR, kungenzeka ukuthi zikhombe futhi ziqinisekise i-biomarker yomfundi e-multic-omic ebikezela ukusinda ezigulini ezinomdlavuza wekoloni. I-dataset ye-Multi-Omic efundayo ihlinzeka ngesisetshenziswa sokuqonda kangcono iColon Cancery Biology futhi usize ukuthola izindlela zokwelapha ezenziwe ngezifiso.
Isikhathi sePosi: Jun-15-2023
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