Leej Met | Ntau-omics ze rau taw qhia cov qog ua ke

Leej Met | Ntau-omics ze rau taw qhia qog, lub cev tsis muaj zog ntawm cov cancer me ntsis kev cuam tshuam txog kev sib cuam tshuam ntawm lub microbiome nrog lub cev tiv thaiv kab mob
Txawm hais tias biomarkers rau tus mob cancer nyhuv tau kawm ntau zaus (MMR) ) los txiav txim cov lus pom zoo kho. Cov kws tshawb nrhiav tau sau tseg tsis muaj kev sib koom ua ke ntawm cov gene kev piav qhia txog kev tiv thaiv kab mob ntshav qab zib (TCGA) Cancer Cancer Cancer (TCGA) Cancer Cancer Court thiab tus neeg mob muaj sia nyob.

Raws li kev tshawb fawb tau nce zuj zus, kom muaj mob qog nqaij hlav cancer, tab sis kuj tseem ceeb tshaj plaws rau kev nkag siab, tab sis kuj tseem muaj kev nkag siab txog kev nkag siab, lossis cov kev sib cuam tshuam microbial, lossis cov kev sib cuam tshuam microbial, tau hais txog qhov lawv muaj kev cuam tshuam ntau yam cuam tshuam rau cov neeg ua kom ua rau tus neeg mob Cov.
Txhawm rau dissect txoj kev sib raug zoo ntawm phenotypic nyuaj thiab cov txiaj ntsig, ib pab neeg tshawb fawb los ntawm cov neeg mob kho mob hauv Qatob contants (ICR). Pab pawg ua kom muaj kev txheeb xyuas cov nqaij khov tshiab ntawm cov qog nqaij hlav, tag nrho cov kab mob T-Cell recensing, ntxiv los ntawm cov qog Genome Securencing mus ntxiv tus yam ntxwv lub microbiome. Txoj kev tshawb no tau luam tawm cov tshuaj uas yog "qog ua qog, kev tiv thaiv kab mob, kev tiv thaiv kab mob microbiome thiab microbiome atlas cancer".

Tshooj lus luam tawm hauv cov tshuaj

AC-ICAM TXHEEJ TXHEEM

Cov kws tshawb nrhiav tau siv cov orthogonal genomic platform los soj ntsuam cov leeg qog nqaij daim tawv thiab cov leeg ua ke ntawm cov neeg mob keeb kwm tsis muaj mob hnyuv. Raws li tag nrho-exome ua ntu zus (wes), RNAq Cov ntaub ntawv zoo tswj, thiab siv cov kev tshuaj xyuas hauv qab nrog kev txheeb xyuas cov nruab nrab ntawm 46 xyoo. Pab pawg tshawb fawb npe hu ua cov khoom siv no Sidra-LumC ac-icam ac-icam act-icam: daim duab qhia chaw rau kev tiv thaiv mob cancer-microbiome (daim duab 1).

Molecular faib siv ICR

Txais cov qauv teeb tsa ntawm kev tiv thaiv kab mob cancer rau kev tsis sib haum xeeb, ICR), hu rau Melanoma, zais pa, thiab Tus mob cancer mis. ICR kuj tau cuam tshuam nrog kev txhaj tshuaj tiv thaiv kab mob tau ua ntau hom kabmob khees xaws, suav nrog tus mob cancer mis.

Ua ntej, cov kws tshawb nrhiav tuaj yeem xaiv lub ICR kos npe ntawm AC-ICAM Cohort, siv ICR cov txheej txheem ua ke los ntawm peb pawg) High ICR (ICR (lub ICR) qog) (daim duab 1b). Cov kws tshawb nrhiav pom tias muaj kev tiv thaiv kab mob tiv thaiv kab mob molecular subtypes (CMS) Lub CMS Pawg suav nrog CMS1 / Txhaj Tshuaj Tiv Thaiv, CMS2 / Canonical, CMS3 / med3 / MMS4 / Mesenchymal. Kev tsom xam tau pom tias ICR cov qhab nia tau cuam tshuam nrog cov kev mob cancer ntawm cov kab mob hauv kev tiv thaiv kab mob thiab kev sib txuam nrog kev tiv thaiv kab mob hauv CMS4.

Hauv txhua CMS, ntau yam ntawm ntuj killer (kk) cell thiab t cell siab impiats (daim duab 1c) .ib). Nyob rau hauv ICR los ntawm tsawg rau siab (Daim duab 1D), piv txwv txoj cai printic lub luag hauj lwm ntawm ICR hauv Colorectal Cancer.

Daim duab 1. AC-icam kawm tsim, cov noob tsis tiv thaiv cov noob pom kev kos npe, kev tiv thaiv kab mob thiab cov ciaj sia taus.
ICR raug ntes cov qog-enriched, clonly amplied t hlwb
Tsuas yog ib haiv neeg tsawg ntawm t hlwb infiltrating cov ntaub so ntswg Yog li ntawd, feem ntau ntawm cov qog t hlwb tau raug xa mus ua tus saib xyuas t hlwb (sectomer t hlwb). Qhov muaj zog sib txheeb nrog cov naj npawb ntawm cov pa ntawm cov hlwb nrog cov khoom lag luam hauv av thiab leukocyte sub-s cell), uas tuaj yeem siv los ntawm RNA-SEq) Nyob rau hauv ICR Clusters (tag nrho cov kev faib tawm), lub siab tshaj plaws ntawm cov tshuaj tiv thaiv kab mob Siv cov transcriptome (18,270 noob) Immunoseq Tmality correlated Ntau dua nrog cov cim loj tshaj qhov kev sib txheeb ntawm cov hlav cd8 + cim (Daim duab 2F thiab 2G). Hauv kev xaus, kev tshawb fawb saum toj no pom tias Icr kos npe ntes muaj cov qog-enliched, clonly amplified t hlwb thiab tej zaum yuav qhia txog cov pellcostic cuam tshuam.

Daim duab 2. Cov qauv ntsuas ntsuas thiab cuam tshuam nrog cov noob tiv thaiv kab mob tiv thaiv kab mob, tsis muaj zog thiab cov suab paj nruag molecular thiab molecular subtypes.
Microbiome muaj pes tsawg leeg hauv kev noj qab haus huv thiab cov ntaub qhwv plab hnyuv
Cov kws tshawb nrhiav tau ua 16s RRNNE EXTRECTION siv DNA rho tawm cov qog nqaij hlav thiab cov neeg mob / tus neeg mob / daim duab 3A). Kev txheeb xyuas qhov tseeb, cov kws tshawb nrhiav ntxiv rau kev txheeb xyuas 16s RRNA noob ua ntu zus uas tsis tau sib phim DNA muaj kev tsom xam. Ua ntej, cov neeg tshawb nrhiav piv cov neeg txheeb ze ntawm cov neeg muaj kev sib raug zoo ntawm cov qog sib phim thiab cov hnyuv tau zoo. Clostridium perfringensens tau nce siab nyob rau hauv cov hlav piv rau cov qauv noj qab haus huv (daim duab 3A-3D). Tsis muaj qhov sib txawv ntawm cov kab mob alpha (ntau haiv neeg thiab cov qauv muaj ntau yam nyob hauv ICR-siab hlav txheeb ze rau ICR-Low hlav.
Txhawm rau txhawm rau txhawm rau cov koom haum tsim nyog ntawm cov qauv me me thiab cov kws tshawb fawb tau npaj kom siv 16s RRNA cov noob ua ntu zus uas kwv yees muaj sia nyob. Ntawm AC-ICAM246, cov kws tshawb nrhiav tau khiav ib qho qauv OS CO COefficients (cuam tshuam nrog kev tuag sib luag (hu ua MBR cov ntsiab lus (Daim Duab 3F).
Hauv qhov kev qhia no (icam246), tus qhab nia MBR tsawg (MBR <0, Tsawg MBB) tau cuam tshuam nrog kev pheej hmoo ntawm kev tuag (85%). Cov kws tshawb nrhiav tau lees paub txog lub koom haum ntawm MBR tsawg (kev pheej hmoo OS hauv ob qho kev siv nyiaj txiag (ICAM42 thiab TCGA-COAD). (Daim duab 3) Qhov kev kawm tau pom tias muaj kev sib cuam tshuam muaj zog ntawm endogastric cocci thiab cov qhab nia MBR, uas tau zoo sib xws hauv cov nqaij qog thiab noj qab nyob zoo hnyuv.

Daim duab 3. Microbiome hauv cov nqaij thiab cov ntaub so ntswg kom zoo thiab kev sib raug zoo nrog ICR thiab tus neeg mob kev muaj sia nyob.
Tag
Cov ntau-omics ze uas siv nyob rau hauv txoj kev kawm no ua kom pom meej meej rau cov molecular kos npe rau cov kev sib cuam tshuam moleector thiab qhia txog kev sib cuam tshuam ntawm lub microbiome thiab lub cev tiv thaiv kab mob. Lub taub hau sib sib zog nqus ntawm cov qog thiab cov ntaub so ntswg zoo uas pom tau tias yog cov qog ua kom cov qog-enriched thiab tej zaum cov qog ua rau lub ntsej muag cell clones.

Los ntawm kev ntsuas cov qog mis microbiome muaj pes tsawg leeg siv 16 Txawm hais tias qhov kos npe no tau muab tau los ntawm cov qog nqaij hlav thiab qog muaj kev phom sij uas yuav ntes lub plab microbiome ntawm cov neeg mob. Los ntawm kev sib txuas nrog cov qhab nia ICR thiab MBR, nws yog qhov ua tau los txheeb xyuas thiab siv tau ntau cov tub ntxhais kawm sib tw uas muaj sia nyob hauv cov neeg mob plab cancer. Txoj kev kawm ntau-omic dataset muab cov peev txheej kom to taub zoo dua kev siv cancer biology thiab pab nrhiav kev nrhiav tus kheej kho kom zoo.

Siv:
Robelands, J., Kuppen, PJK, Ahmed, EI li al. Ib qho kev sib xyaw ua qog, kev tiv thaiv kev tiv thaiv kab mob thiab microbiome thiab cov kabmob ntawm tus hnyuv. NAT Medi-29, 1273-1286 (2023).