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Nat Med | Uburyo bwo gukoresha uburyo bwinshi bwo gushushanya imiterere y’ikibyimba, ubudahangarwa bw’umubiri n’imikorobe bya kanseri y’inkondo y’umura bugaragaza imikoranire y’imikorobe n’ubudahangarwa bw’umubiri.
Nubwo ibimenyetso by’indwara za kanseri y’inkondo y’umura byigwa cyane mu myaka yashize, amabwiriza y’ubuvuzi akoreshwa ubu ashingira gusa ku gupima no kumenya ubusembwa bwa ADN (MMR) cyangwa kutamenya neza uburyo ADN ikora (MSI) (uretse gupima indwara bisanzwe) kugira ngo hamenyekane inama zo kuvura. Abashakashatsi bagaragaje ko nta sano riri hagati y’ubwiyongere bw’ubudahangarwa bushingiye ku miterere y’uturemangingo, imiterere ya mikorobe, na kanseri itera kanseri mu itsinda rya kanseri y’inkondo y’umura rya Cancer Genome Atlas (TCGA) n’ubuzima bw’abarwayi.
Uko ubushakashatsi bwagiye butera imbere, imiterere y’imibare ya kanseri y’inkondo y’umura, harimo kanseri y’uturemangingo, ubudahangarwa bw’umubiri, stromal, cyangwa mikorobe, byagaragaye ko bifitanye isano rikomeye n’ibisubizo by’ubuvuzi, ariko haracyari ubumenyi buke ku buryo imikorere yazo igira ingaruka ku murwayi.
Kugira ngo basobanukirwe isano iri hagati y’ubuhanga bw’ibintu bihinduka n’umusaruro, itsinda ry’abashakashatsi bo mu Kigo cya Sidra cy’Ubushakashatsi mu by’Ubuvuzi muri Qatar baherutse gukora no kwemeza amanota ahuriweho (mICroScore) agaragaza itsinda ry’abarwayi bafite igipimo cyiza cyo kubaho binyuze mu guhuza imiterere ya mikorobe n’ibintu bihoraho byo kwanga ubudahangarwa bw’umubiri (ICR). Itsinda ryakoze isesengura ryimbitse rya genomike ku ngero nshya zakonjeshejwe z’abarwayi 348 barwaye kanseri y’inkondo y’umura, harimo gukurikirana RNA y’ibibyimba n’ingingo nzima y’inkondo y’umura, gukurikirana exome yose, receptor y’uturemangingo twa T twimbitse na gene ya 16S ya bagiteri rRNA, hiyongereyeho gukurikirana genome yose y’ibibyimba kugira ngo harusheho kugaragara mikorobe. Ubu bushakashatsi bwasohotse muri Nature Medicine nka “Ikibyimba gihuriweho, immuno na microbiome atlas ya kanseri y’inkondo y’umura”.
Ingingo yasohotse mu gitabo cy'ubuvuzi bw'ibidukikije
Incamake ya AC-ICAM
Abashakashatsi bakoresheje urubuga rwa genomike rwa orthogonal kugira ngo basesengure ingero z'ibibyimba bishya byakonjeshejwe kandi bahuza ingirabuzima fatizo z'amara zimeze neza zegeranye (ibibyimba-bisanzwe) by'abarwayi banduye kanseri y'amara nta miti ikoreshwa mu buryo bw'umubiri. Hashingiwe ku gusesengura imyakura yose (WES), kugenzura ubuziranenge bw'amakuru ya RNA-seq, no gusuzuma ibipimo byo kuyishyira mu bikorwa, amakuru ya genomike yavuye mu barwayi 348 yagumanywe kandi akoreshwa mu gusesengura igice cya nyuma cy'isuzuma, hagakurikiranwa imyaka 4.6. Itsinda ry'abashakashatsi ryise iyi nkomoko Sidra-LUMC AC-ICAM: Ikarita n'ubuyobozi ku mikoranire y'ubudahangarwa bw'umubiri-kanseri-mikorobe (Ishusho ya 1).
Gushyira mu byiciro molekile hakoreshejwe ICR
Itsinda ry’ubushakashatsi ryafashe urutonde rw’ibimenyetso by’imiterere y’umubiri mu gusuzuma kanseri mu buryo buhoraho, byitwa immunoconstant of rejection (ICR), ryanogeje ICR riyishyira mu itsinda ry’uturemangingo 20 dukubiyemo ubwoko butandukanye bwa kanseri, harimo melanoma, kanseri y’uruhago, na kanseri y’ibere. ICR yanahujwe no gutanga ubufasha mu kuvura kanseri mu bwoko butandukanye bwa kanseri, harimo na kanseri y’ibere.
Ubwa mbere, abashakashatsi bemeje ikimenyetso cya ICR cy’itsinda rya AC-ICAM, bakoresheje uburyo bwa ICR bushingiye ku ngirabuzimafatizo kugira ngo bashyire itsinda mu byiciro bitatu by’itsinda ry ...
Muri CMS zose, ubwinshi bw'uturemangingo tw’umubiri twica karemano (NK) n'uturemangingo twa T bwari hejuru cyane mu turemangingo tw’umubiri twica cyane twa ICR, hamwe n’itandukaniro rikomeye mu tundi turemangingo tw’amaraso duto (leukocyte subsets) (Ishusho ya 1c). Uturemangingo tw’umubiri twica cyane twa ICR twari dufite OS na PFS zitandukanye, hamwe n’ubwiyongere bukomeje bwa ICR kuva hasi kugera hejuru (Ishusho ya 1d), byemeza uruhare rwa ICR mu gutanga amakuru kuri kanseri y’inkondo y’umura.
Ishusho ya 1. Igishushanyo mbonera cy'ubushakashatsi bwa AC-ICAM, ikimenyetso cya gene kijyanye n'ubudahangarwa bw'umubiri, ubwoko bw'ubudahangarwa bw'umubiri n'uturemangingo hamwe n'ubuzima.
ICR ifata uturemangingo twa T twiyongera ku turemangingo tw’ibibyimba kandi twongerewe imbaraga mu mikorere yatwo
Ni bake cyane mu turemangingo twa T twinjira mu turemangingo twa kanseri byavuzwe ko ari two twihariye ku ma antigen ya kanseri (munsi ya 10%). Kubwibyo, inyinshi mu turemangingo twa T turi mu turemangingo twitwa uturemangingo twa T twitabye Imana (uturemangingo twa T twitabye Imana). Isano ikomeye cyane n'umubare w'uturemangingo twa T dusanzwe dufite TCR zitanga umusaruro yagaragaye mu turemangingo twa stromal na leukocyte (byabonetse hakoreshejwe RNA-seq), dushobora gukoreshwa mu gupima uturemangingo twa T (Ishusho ya 2a). Mu matsinda ya ICR (muri rusange no mu cyiciro cya CMS), imiterere myinshi ya TCRs z'ubudahangarwa yagaragaye mu matsinda ya CMS1/immunite ya ICR-high na CMS (Ishusho ya 2c), hamwe n'umubare munini w'uturemangingo twa ICR-high. Hakoreshejwe transcriptome yose (genes 18.270), genes esheshatu za ICR (IFNG, STAT1, IRF1, CCL5, GZMA, na CXCL10) zari muri genes icumi za mbere zifitanye isano na TCR immunosequence clonality (Ishusho ya 2d). Ubuziranenge bwa ImmunoSEQ TCR bwahuye cyane n’uturemangingo twinshi twa ICR kuruta isano ryagaragaye hakoreshejwe ibimenyetso bya CD8+ birwanya kanseri (Ishusho ya 2f na 2g). Mu gusoza, isesengura ryavuzwe haruguru rigaragaza ko ikimenyetso cya ICR kigaragaza ko hari uturemangingo twa T twiyongera ku turemangingo kandi dushobora gusobanura ingaruka zabyo mu gihe cy’ibizamini.
Ishusho ya 2. Ibipimo bya TCR n'isano bifitanye n'uturemangingo dufitanye isano n'ubudahangarwa bw'umubiri, ubwoko bw'ubudahangarwa bw'umubiri n'uturemangingo.
Imiterere ya mikorobe mu turemangingo twa kanseri y'amara meza n'uturemangingo tw'inkondo y'umura
Abashakashatsi bakoze sequencing ya 16S rRNA bakoresheje ADN yakuwe mu kibyimba gihuye n’uturemangingo tw’amara tuzima twavuye ku barwayi 246 (Ishusho ya 3a). Kugira ngo byemezwe, abashakashatsi banasesenguye amakuru y’uburyo gene ya 16S rRNA ikurikirana kuva mu bindi bipimo 42 by’ibibyimba bitari bifite ADN isanzwe yashoboraga gupimwa. Ubwa mbere, abashakashatsi bagereranije ubwinshi bw’ibimera hagati y’ibibyimba bihuye n’uturemangingo tw’amara tuzima. Clostridium perfringens yiyongereye cyane mu turemangingo ugereranije n’uturemangingo tw’amara tuzima (Ishusho ya 3a-3d). Nta tandukaniro rinini ryagaragaye mu bwoko bwa alpha (ubwoko butandukanye n’ubwinshi bw’ubwoko mu rugero rumwe) hagati y’uturemangingo tw’ibibyimba n’uturemangingo tuzima, kandi kugabanuka guke mu bwoko bwa mikorobe byagaragaye mu turemangingo dufite ICR nyinshi ugereranyije n’uturemangingo dufite ICR nke.
Kugira ngo bamenye isano iri hagati y’imiterere ya mikorobe n’ibisubizo by’ubuvuzi, abashakashatsi bagamije gukoresha amakuru ya 16S rRNA gene sequencing kugira ngo bamenye imiterere ya mikorobe iteganya ko izarokoka. Muri AC-ICAM246, abashakashatsi bakoze moderi ya OS Cox regression yatoranyije imiterere 41 ifite coefficients zitari zeru (zifitanye isano n’ingaruka z’urupfu), yitwa MBR classifiers (Ishusho ya 3f).
Muri iri tsinda ry’amahugurwa (ICAM246), amanota make ya MBR (MBR<0, MBR nke) yahujwe n’ibyago bike cyane byo gupfa (85%). Abashakashatsi bemeje isano iri hagati ya MBR nke (ibyago) na OS ihoraho mu matsinda abiri yemewe ku giti cyabo (ICAM42 na TCGA-COAD). (Ishusho ya 3) Ubushakashatsi bwagaragaje isano ikomeye hagati ya endogastric cocci na MBR, byari bisa mu tubyimba no mu mara mazima.
Ishusho ya 3. Imikorobe mu turemangingo n'uturemangingo tuzima hamwe n'isano iri hagati ya ICR n'ubuzima bw'umurwayi.
Umwanzuro
Uburyo bwa multi-omics bwakoreshejwe muri ubu bushakashatsi butuma habaho gusesengura no gusuzuma neza ikimenyetso cy’ubwirinzi bw’umubiri muri kanseri y’inkondo y’umura, kandi bugagaragaza imikoranire iri hagati ya mikorobe n’ubudahangarwa bw’umubiri. Gukurikirana byimbitse TCR ku ndwara ya kanseri n’uturemangingo tuzima byagaragaje ko ingaruka za ICR zishobora guterwa n’ubushobozi bwayo bwo gufata utunyangingo twa T twakuwemo kanseri ndetse n’utunyangingo dushobora kuba twihariye.
Mu gusesengura imiterere ya mikorobe y’ikibyimba hakoreshejwe uburyo bwa 16S rRNA gene mu bipimo bya AC-ICAM, itsinda ryabonye ikimenyetso cya mikorobe (amanota ya MBR) gifite agaciro gakomeye ko guhanura. Nubwo iki kimenyetso cyavuye mu bipimo bya mikorobe, hari isano ikomeye hagati y’amanota meza y’uruhu rw’imbere rw’umura n’amanota ya MBR y’ikibyimba, bigaragaza ko iki kimenyetso gishobora gufata imiterere ya mikorobe y’umura w’abarwayi. Mu guhuza amanota ya ICR na MBR, byashobotse kumenya no kwemeza ikigereranyo cy’inyigo y’abanyeshuri benshi gihanura ko abarwayi ba kanseri y’umura bazarokoka. Amakuru y’ubushakashatsi ya multi-omic atanga isoko yo gusobanukirwa neza ibinyabuzima bya kanseri y’umura no gufasha kuvumbura uburyo bwihariye bwo kuvura.
Igihe cyo kohereza: Kamena-15-2023
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