I-NAM MED | Indlela ye-onics ye-osics ye-imeyile ye-tumoor edibeneyo

I-NAM MED | Indlela ye-onics ye-osics ye-tumor ye-tumoor ye-tumation, i-microfial yomhlaza we-colorecy ibonisa ukusebenzisana kwe-microbiome ngenkqubo yomzimba
Nangona ii-biomarkers ze-colon eziphambili zifundwe kakhulu kwiminyaka yakutshanje, izikhokelo zekliniki ezikhoyo ngoku zixhomekeke kuphela kwi-tumar-lymphet kunye nokungazinzi kwe-tumor-lmrph okanye ukungazinzi kwe-DNA MSMETH kunye nokuzibandakanya kwe-DNA MEMORK kunye (ukongeza kuvavanyo lonyango) ukumisela izindululo zonyango. Abaphandi baqaphele ukunqongophala kokunxulumana phakathi kweempendulo ezisekwe kwi-fur

Njengoko uphando luye lwaqhubeka, iimpawu zobungakanani bomhlaza oyintloko, kubandakanya nomhlaza weeselula, ukhuselo, ukuthathwa komhlaza, kodwa kuxelwe ukuba kulungiswe iziphumo zeklinikhi, kodwa kusekho ukuqonda okuncinci kwindlela abachaphazela ngayo iziphumo zesigulana.
Ukuphambuka ubudlelwane phakathi kobunzima be-phenotypic kunye nesiphumo, iqela labaphandi abakwi-Sidra Iziko lophando kwi-qatar kutshanje (i-Microscore) eqinisekisa ukuba iphawu le-microbiome i-standers (i-ICR). Eli qela lenze uhlalutyo olubanzi lweesampulu ezifumileyo ezivela kwizigulana ezingama-348 ezinomhlaza wokuqala omiselweyo, i-tishu ye-ticulting ye-TACEAT, i-SE-CORTAL SEATERE, iyongezelelo ye-genolog ye-genome ye-genome ye-genome yokuqhubela phambili i-microbiome. Olu phando lwapapashwa kwiyeza lendalo 'njenge-tumoor edibeneyo, amagorha kunye ne-roniorme ye-atlas yomhlaza weKolon ".

Inqaku elipapashwe kwiPhicodyuli leNdalo

Amagqabantshintshi e-AC-ICAM

Researchers used an orthogonal genomic platform to analyze fresh frozen tumor samples and matched adjacent healthy colon tissue (tumor-normal pairs) from patients with a histologic diagnosis of colon cancer without systemic therapy. Ngokusekwe kwi-onmeemeding epheleleyo (Wes), uLawulo lweDatha-Seq qOq dat, kunye nokunqongophala kwendlela yokubandakanywa, idatha ye-genomic ukusuka kuhlalutyo lweminyaka engama-348 kunye nokusetyenziswa kweminyaka emi-448. IQela loPhando eligama lingu-Sidra-Lumc Ac-Icam: Imephu kunye nesikhokelo kwi-cer-microbiome itrance-microbiome.

Ukwahlulahlula-hlulwa kwemolekyuli kusetyenziswa i-ICR

Ukufaka idatha yeseti yemodyuli yofunyazo yokuqubuka kwemfuza yomhlaza we-furlouner eqhubekayo, ebizwa ngokuba yi-ICR yokuKhulula (i-ICR), iQela loPhando liphumeza i-ICR ngokusifaka kwi-ICR ngokusingisa kwi-ICR ngokuqhuba i-ICR ngokwenza umhlaza we-gener, kubandakanya umhlaza we-bidlame, kunye nomhlaza we-bladring, kunye nomhlaza we-bladring, kunye nomhlaza webhulukhwe. I-ICR ikwanxulunyaniswa nempendulo elumkileyo kwiintlobo ezahlukeneyo zomhlaza, kubandakanya nomhlaza webele.

Okokuqala, abaphandi baqinisekisa ukutyikitywa kwe-ICR ye-AC-I-ICR, esebenzisa indlela ye-ICR yohlobo lwe-ICR yokuphucula i-COSTTER KWI-CRUSTSE KWI-CRUSTER KWI-CRUST YENCWADI KWI-CRUSTER KWI-CRUSTER KWI-CRUSTES / I-ICR ephezulu (i-ICR ephezulu). Abaphandi baphawula ubujondolozisi obunxulunyaniswa nezivumelwano zembumbulu (i-CMS), ukuhlelwa okusekwe kwi-colon. Iindidi ze-CMS zibandakanya i-CMS1 / igogo, i-CMS2 / i-canon2 / i-CMS3 / metabolic kunye ne-CMS4 / Meseshmey. Uhlalutyo lubonise ukuba amanqaku e-ICR adityaniswe kakubi ngefowuni ethile yomhlaza kuzo zonke iindlela ze-CMS, kunye nokulungiswa okuqinisekileyo kunye neendlela ezinxulumene ne-itromosupprestives kunye ne-stromal.

Kuzo zonke ii-CMS, ubuninzi bendalo (i-NK) yeselfowuni kunye ne-T) i-ICRTPUP ephakamileyo ye-ICR kunye ne-1C 1C), i-1c 1C), iqinisekisile indima ye-ICR kwi-ICR kwi-ICR kwi-ICR kwi-ICR kwi-ICR kwi-ICR.

Umzobo 1. Uyilo lwe-Ac-I-AC-I-AC-I-ACSTE YOKUGQIBELA I-Gene-Sign-Sign-Sign-Genes Sam kunye ne-Molecrossul Subtypes kunye nokusinda.
I-ICR ithintela i-tumor-ityesikile ye-TUREART ye-TUREALS
Kuphela kukungabinamncinci kweeseli ze-T ezingacocekanga zichazwe ukuba zichaziwe kwi-tuma i-turuen (ngaphantsi kwe-10%). Ke ngoko, uninzi lweeseli ze-Intra-Tumor T lubhekiselwa kwiiseli ze-Tystander (iiseli ze-Bitter T). Unxibelelwano oluqinileyo nenani leeseli ze-T eziqhelekileyo ezinee-TCR ezinemveliso ziqwalaselwe kwiseli ye-stromal kunye ne-leukicyte subpopulations (ifunyenwe yi-RNA-SEQ), enokusetyenziselwa ukuqikelela i-T Kwiqela le-ICR (iyonke kunye ne-CMS yokwahlulahlula), eyona ndawo iphezulu ye-SEQ ye-SEQ yaqwalaselwa kwi-ICR-right kunye ne-CMS2 / GEMOPE CMS1 / Generem 2C 2C (Umzobo 2C), kunye ne-ICR-EPURSE ye-ICR-high namathumba aphezulu. Sebenzisa yonke imiphetho (i-18,270 ye-genes), i-ict emithandathu ye-ICR (i-I-Itf1, i-IRF1, i-IRF1, i-CCL5, i-CCMA10) idityaniswe ne-gesn yeshumi le-STC ImmunoSEQ TCR clonality correlated more strongly with most ICR genes than the correlations observed using tumor-responsive CD8+ markers (Figure 2f and 2g). Ukuqukumbela, uhlalutyo olungentla lubonisa ukuba isiginitsha ye-ICR ithatha ubukho be-turus-turud T

Umzobo 2. I-Tracc ye-metrics kunye ne-colrereting eneziphene ezinxulumene nezomzimba, ukhuselo kunye nemolekyuli.
Ubume be-microbiome kwizicubu zempilo ne-colon
Abaphandi benze i-16s Rrna ukulandelelana kokusebenzisa i-DNA ekhutshwe kwi-tumor ene-tumas kunye ne-colon esempilweni evela kwizigulana ezingama-246 (umzobo 3a). Ukuqinisekiswa, abaphandi abongezayo nge-16s RRNA ye-GRNA yokulandelelana kwezinto ezingama-42 ze-tumor ezazingenayo i-DNA eqhelekileyo ekhoyo yohlalutyo. Okokuqala, abaphandi bathelekisa intabalala ye-flora phakathi kwamathumba athambileyo kunye nezicubu zempilo. I-Clotoriridium Profringns yayinyuswa kakhulu kwi-tumurs xa kuthelekiswa neesampulu zempilo (umzobo 3a-3D). Kwakungekho mahluko ubalulekileyo kwimahluko (iyantlukwano kunye nobuninzi beentlobo zesampulu enye) phakathi kwe-tumor kunye neesampulu ezinempilo, kunye nokuncitshiswa okuphakathi kwe-iCR-up
Ukufumana iMibutho efanelekileyo eklinikhi phakathi kweeprofayili ze-ratial kunye neziphumo zeklinikhi, abaphandi bajolise ekusebenziseni idatha ye-16s RRNA yokuchonga iimpawu ezibonisa ukusinda. Kwi-AC-ICAM246, abaphandi baqhuba imodeli ye-OS ye-OS ekhethiweyo eyi-41 ye-Erogrigy (enxulumene ne-mbr classifiers (umzobo 3f).
Kolu qeqesho i-cohort (i-ICAM246), inqaku le-MBR le-MBR (i-MBR <0, i-MBRE) yadityaniswa nomngcipheko ophantsi wokufa (85%). Abaphandi baqinisekisile ubudlelwane phakathi kwe-MBr ephantsi (umngcipheko) kunye ne-os e-OS kwi-ohorts ezimbini eziqinisekileyo eziqinisekileyo (i-ICAM42 kunye ne-TCGA-Coad). .

Umzobo 3. I-microbiome kwi-tumor kunye nezicubu ezinempilo kunye nolwalamano ne-ICR kunye ne-ICR nakwisimo soMonde.
Ukuqukumbela
Inkqubo ye-onics yemidlalo emininzi esetyenziswa kolu phando isebenzisa imvume echanekileyo kunye nohlalutyo lwesiginitsha yemolekyuli kumhlaza omiselweyo kwaye ityhila unxibelelwano phakathi kwe-microbiome kunye namajoni omzimba. Deep TCR sequencing of tumor and healthy tissues revealed that the prognostic effect of ICR may be due to its ability to capture tumor-enriched and possibly tumor antigen-specific T cell clones.

Ngokuhlaziya ubume be-tumor microbiome usebenzisa iisampulu ze-16s ze-genen kwi-AC-i-I-I-AC-IIAM, iqela lichonge isiginitsha ye-microbiome (i-MBR yengozi) enexabiso eliqingqiweyo. Nangona esi siginisayina sasungulwa kwiisampulu zethumba, kwabakho unxibelelwano olunamandla phakathi kweCollorem esempilweni kunye ne-tumar mbr yomngcipheko, ephakamisa ukuba esi sisayine sinokuthi sithathe imigudu ye-Gut. Ngokudibanisa i-ICR kunye namanqaku e-MBR, kunokwenzeka ukuba uchonge kwaye uqinisekise i-biamer yomfundi ongumfundi oqiqayo oxela ukusinda kwizigulana ezinempili. Idatha ye-data ye-One-Ommic ye-o-os ibonelela ngesixhobo sokuyiqonda ngcono i-biology bimboigy kwaye incede ufumane iindlela zonyango.

Isalathiso:
UReelands, uJ., Kuppen, pjk, i-ahmed, et al al. I-tumoor edibeneyo, i-microbiome itlas yomhlaza weKolon. I-NAD MED 29, 1273-1286 (2023).