Nat Med | Uburyo bwinshi bwo gukora kugirango akoreshe ikibyimba cyuzuye

Nat Med | Ikibanza cyahamije gisanzwe cyo gushushanya ikibyimba cyuzuye, kanseri ya kanseri ya mikorobe igaragaza imikoranire ya mikorobile hamwe na sisitemu yumubiri
Nubwo ibinyabuzima kuri kanseri y'ibanze ya Colon Chised cyane mu myaka yashize, umurongo w'amavuriro uriho ushingiye gusa kuri tumor-lymph node. Kumenya neza Abashakashatsi bavuze ko kubura ishyirahamwe hagati ya Gene mvugo - imyirondoro ya mikorobe, kandi ikibyimba cya kanseri ya kanseri ya kanseri (TCGA).

Nkuko ubushakashatsi bwateye imbere, buranga ibintu bya kanseri yibanze, harimo kanseri ya kanseri, ubudahangarwa, cyangwa mikorobe ya kanseri, ariko haracyariho gutondekanya imiterere yubuvuzi, ariko haracyariho gusobanukirwa neza nuburyo imikoranire yabo igira ingaruka kumikoranire yibayita.
Gutandukanya umubano hagati yuburwayi bwa phenotypic nibisubizo, itsinda ryabashakashatsi baturutse mu bushakashatsi bwa Sidra mu bushakashatsi bwa sidra muri Qatar, bugaragaza amanota y'imiterere (Microscore) agereranya ibiranga microbiome no kwangwa kwubudahanga (ICR). Ikipe yakoze isesengura ryuzuye ryimpapuro nshya zifunzwe kuva 348 zirimo kanseri yibanze, harimo na RRNES zihuye na RRNE zihuye na RRNE za TRna, zuzura ibibyimba byose bya Genomen. Ubushakashatsi bwasohotse mu miti ya kamere nk "ikibyimba rusange, ubudahangarwa na microbiome atlas ya kanseri ya colon".

Ingingo yasohotse mu buvuzi bwa kamere

AC-ICAM Incamake

Abashakashatsi bakoresheje urubuga rwa erthogonal yo gusesengura ibibyimba bishya byafunzwe kandi bihuye neza (ibibyimba-bisanzwe) bivuye mu barwayi bafite isuzuma rya kanseri ya Colon nta muti. Dushingiye ku gishushanyo mbonera cyagaciro (wes), kugenzurwa na RNA-SEQ, hamwe n'ibipimo ngenderwaho byo mu barwayi 348 byagumishijwe no gusesengura imyaka 4.6. Ikipe y'Ubushakashatsi yise aya makuru Sidra-Lumc Ac-lumc: Ikarita n'Ubuyobozi mu mikoranire ya microbiome-microbiome (Ishusho 1).

Ibyiciro bya molekile ukoresheje ICR

Gufata modular Ibimenyetso bidahunze imirimbayi kuri kanseri ihoraho, yise umudayimoni uhora wangwa (ICR). ICR nayo yahujwe nigisubizo cya imbinotherapi muburyo butandukanye bwa kanseri, harimo na kanseri y'ibere.

Ubwa mbere, abashakashatsi bemeje umukono wa ICR wa AC-ICAM COHORT, ukoresheje uburyo bwo gupima Icce kugirango bakore cluster eshatu / ubudahangarwa bwa ICR (ibibyimba bishyushye) (Ishusho ikonje) (Ishusho 1b). Abashakashatsi baranga umuhanga uhuza na ubwumvikane bwa moleculas. Ibyiciro bya CMS birimo CMS1 / ubudahangarwa, CMS2 / Canonsical, CMS3 / Metabolic na CMS4 / Mesenchymal. Isesengura ryerekanwe nabi ninzira nyabagendwa na kanseri ya kanseri muri CMS yose, kandi ihuriweho ryiza ninzira nyabagendwa kandi zijyanye na Stromal zagaragaye gusa muri CMS4.

Muri CMS yose, ubwinshi bwa killer karemano (NK) selile na T Akagari kari hejuru muri ICR kuva muri ICR kuva hasi (Igishushanyo cya 1C), zerekana uruhare runini muri kanseri yingenzi.

Igishushanyo 1. Igishushanyo mbonera cyo kwiga, umukono wa gene ubudahuza, ubudahangarwa nuburinganire na molekari subtypes no kubaho.
ICR yafashe ikibyimba-ikungahaza, Yongerewe ya T.
Gusa na talile nkeya gusa yoroheje ibibyimba tissue yavuzwe ko yihariye ibibyimba (munsi ya 10%). Kubwibyo, benshi mu maboko ya TTRA-trangirangero zivugwa ko ari selile za T. (kure ya T. Ihuza rikomeye n'umubare wa T.Binuro isanzwe ya TCRS yagaragaye mu kagari ka Stromal na Leukocyte (byagaragaye na RNA-SEQ), bishobora gukoreshwa mu kugereranya na t seltpoputions (Ishusho 2a). Muri ICR Cluster (Muri rusange na CMS Ibyiciro Byinshi Byonyine TCR yiziritse muri ICR-hejuru na cms subtype cms1 / amatsinda yubudahangarwa. Ukoresheje ibipimo byose bya transcriptome (genes 18.270) Imyugokeq TCR Clonality ifitanye isano cyane nibisobanuro byinshi bya ICR kuruta ubufatanye bwagaragaye ukoresheje CD8 yo kwitabaza CD8 (Ishusho 2G). Mu gusoza, isesengura ryavuzwe haruguru ryerekana ko umukono wa ICR uhamye ikibyimba cya T.

Igishushanyo cya 2. Ibipimo bya TCR hamwe nubusa hamwe na genes zijyanye nabadahuzabilime, ubudahangarwa nuburinganire.
Microbiome ibihimbano mu buzima bwiza kandi bwa Colon
Abashakashatsi bakoreye 16s rukurikirana ya DRNA ukoresheje ADN yakuwe mu bibyimba bihuye hamwe na colon ifite ubuzima bwiza kuva abarwayi 246 (Ishusho 3a). Kubyemezo byongeye gusesengura amakuru 16s RRNE ya DRNA ivuye ku byitegererezo 42 byibibyimba bitajyanye na ADN isanzwe iboneka kubisesengura. Ubwa mbere, abashakashatsi bagereranije ingano ugereranije na flora hagati y'ibibyimba bihuye hamwe na colon nziza. Clostridium perfringnans yiyongereye cyane mubibyimba ugereranije nicyitegererezo cyiza (Ishusho 3a-3d). Nta tandukaniro rikomeye muri Alpha itandukanye (Ubusa n'ubwoko bwinshi mu cyitegererezo kimwe) hagati y'ibibyimba bitandukanye n'ibyiyumvo byashyizwe mu bibyimba byashyizwe mu bice bya ICR-bike.
Kugirango umenye amashyirahamwe yubuvuzi hagati yimyirondoro ya Microbial hamwe nabashakashatsi bagize intego yo gukoresha amakuru 16s rukurikirana kugirango bamenye imiterere microbiome ibiranga kubaho. Kuri AC-icam246, abashakashatsi bayoboye icyitegererezo cya OS COX COX cyatoranijwe hamwe na coeffictions zitari zeru (zijyanye ningaruka zimpinduka zitandukanijwe), zitwa imbr (Ishusho ya 3F).
Muri aya mahugurwa (icam246), amanota make ya Mbr (MBR <0, Mbr hasi) yari ifitanye isano nigitekerezo cyo hasi cyane cyurupfu (85%). Abashakashatsi bemeje ishyirahamwe riri hagati ya mbr hasi (ibyago) kandi ndende os mu bice bibiri byigenga (ICAM42 na Tcga-coad). .

Igishushanyo cya 3. Microbiome mubyigindo hamwe ningingo zizima nubusabane na ICR no kubaho kwihangana.
Umwanzuro
Uburyo bwinshi-bukoreshwa muri ubu bushakashatsi butanga kumenya neza no gusesengura byuzuye umukono wa molecular wa kanseri ya gare kandi agaragaza imikoranire hagati ya microbiome na sisitemu yumubiri. Urutonde rwa TCR rwimbitse hamwe ningingo zizima zagaragaje ko ingaruka zikomeye za ICR zishobora guterwa nubushobozi bwayo bwo gufata ikibyimba-gushingwa kandi birashoboka-clon-selile.

Mugusesengura ibibyimba bya microbiome ukoresheje 16s na RRNE ya RRNE ya AC-ICAM yerekanye umukono wa microbiome (amanota ya Mbr) afite agaciro gakomeye. Nubwo uyu mukono wakomotse ku byitegererezo, habaye isano ikomeye hagati ya coloretum nziza hamwe nitsinda ryibishanga rya mbr, ryerekana ko uyu mukono wawe ushobora gufata imikono ya git mikorobe yabarwayi. Muguhuza amanota ya ICR na MBR, byashobokaga kumenya no kwemeza ibinyabuzima byinshi byabandi bahoze ari abayirwandakazi bahanura kubaho mubarwayi bafite kanseri ya colon. Ubushakashatsi bwakozwe kuri byinshi butanga ibikoresho kugirango bumve neza ibinyabuzima bya kanseri ya kanseri no gufasha kumenya uburyo bwo gutanga ubwatsi bwihariye.

Reba:
Roelay, J., Kupuro, PJK, Ahmed, EI et al. Ikibyimba cyinjijwemo, ubudahangarwa na microbiome atlas ya kanseri ya colon. Nat Mad 29, 1273-1286 (2023).