Mob qog noj ntshav pancreatic yog ib qho ntawm cov qog nqaij hlav tuag coob tshaj plaws hauv ntiaj teb nrog kev pom tsis zoo.Yog li ntawd, yuav tsum muaj tus qauv kev kwv yees kom raug txhawm rau txheeb xyuas cov neeg mob uas muaj kev pheej hmoo siab mob qog noj ntshav rau kev kho mob thiab txhim kho cov kev mob tshwm sim ntawm cov neeg mob no.
Peb tau txais Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq cov ntaub ntawv los ntawm UCSC Xena database, txheeb xyuas lub cev tiv thaiv kab mob lncRNAs (irlncRNAs) los ntawm kev txheeb xyuas kev sib raug zoo, thiab txheeb xyuas qhov sib txawv ntawm TCGA thiab ib txwm muaj kab mob pancreatic adenocarcinomas.DEirlncRNA) los ntawm TCGA thiab genotype cov ntaub so ntswg qhia (GTEx) ntawm cov ntaub so ntswg pancreatic.Ntxiv univariate thiab lasso regression tsom xam tau ua los tsim prognostic kos npe qauv.Tom qab ntawd peb suav cov cheeb tsam hauv qab qhov nkhaus thiab txiav txim siab qhov kev txiav tawm zoo tshaj plaws rau kev txheeb xyuas cov neeg mob uas muaj kab mob pancreatic adenocarcinoma siab thiab qis.Txhawm rau sib piv cov yam ntxwv kho mob, kev tiv thaiv kab mob hauv lub cev, kev tiv thaiv kab mob microenvironment, thiab tshuaj tua kab mob hauv cov neeg mob uas muaj mob qog noj ntshav siab thiab qis qis.
Peb tau txheeb xyuas 20 DEirlncRNA khub thiab pab pawg neeg mob raws li qhov pom zoo txiav tawm tus nqi.Peb tau ua pov thawj tias peb tus qauv kos npe prognostic muaj qhov ua tau zoo hauv kev kwv yees cov neeg mob nrog PAAD.AUC ntawm ROC nkhaus yog 0.905 rau 1-xyoo kev kwv yees, 0.942 rau 2-xyoo kev kwv yees, thiab 0.966 rau 3-xyoo kev kwv yees.Cov neeg mob uas muaj kev pheej hmoo siab tau qis dua cov ciaj sia taus thiab cov yam ntxwv kho mob tsis zoo.Peb kuj tau pom tias cov neeg mob uas muaj kev pheej hmoo siab tiv thaiv kab mob thiab tuaj yeem txhim kho kev tiv thaiv kab mob.Kev ntsuam xyuas cov tshuaj tiv thaiv kab mob xws li paclitaxel, sorafenib, thiab erlotinib raws li cov cuab yeej suav nrog kev kwv yees yuav tsim nyog rau cov neeg mob uas muaj kev pheej hmoo siab nrog PAAD.
Zuag qhia tag nrho, peb txoj kev tshawb fawb tau tsim cov qauv kev pheej hmoo pheej hmoo tshiab raws li kev sib koom ua ke irlncRNA, uas pom tau tias muaj txiaj ntsig zoo rau cov neeg mob qog noj ntshav pancreatic.Peb cov qauv kev pheej hmoo pheej hmoo yuav pab sib txawv cov neeg mob nrog PAAD uas tsim nyog rau kev kho mob.
Mob qog noj ntshav pancreatic yog ib qho mob qog nqaij hlav uas tsis muaj sia nyob tsib xyoos thiab qib siab.Thaum lub sijhawm kuaj mob, cov neeg mob feem ntau twb nyob rau theem siab heev.Nyob rau hauv cov ntsiab lus ntawm COVID-19 kev sib kis, cov kws kho mob thiab cov kws saib xyuas neeg mob muaj kev nyuaj siab loj thaum kho cov neeg mob qog nqaij hlav pancreatic, thiab cov neeg mob cov tsev neeg kuj ntsib ntau yam kev ntxhov siab thaum txiav txim siab kho mob [1, 2].Txawm hais tias muaj kev nce qib zoo hauv kev kho mob ntawm DOADs, xws li kev kho neoadjuvant, kev phais phais, kev kho hluav taws xob, tshuaj khomob, kev kho mob molecular, thiab kev tiv thaiv kab mob tiv thaiv kab mob (ICIs), tsuas yog li 9% ntawm cov neeg mob muaj sia nyob tsib xyoos tom qab kuaj pom [3 ].], 4] ib.Vim tias cov tsos mob ntxov ntawm pancreatic adenocarcinoma yog atypical, cov neeg mob feem ntau raug kuaj pom tias muaj metastases nyob rau theem siab [5].Yog li ntawd, rau ib tus neeg mob, kev kho mob ib leeg yuav tsum ntsuas qhov zoo thiab qhov tsis zoo ntawm txhua txoj kev kho mob, tsis yog tsuas yog ua kom muaj sia nyob ntev, tab sis kuj txhim kho lub neej zoo [6].Yog li ntawd, tus qauv kev kwv yees ua tau zoo yog qhov tsim nyog los ntsuas qhov tseeb ntawm tus neeg mob qhov kev cia siab [7].Yog li, kev kho mob tsim nyog tuaj yeem raug xaiv kom sib npaug ntawm kev ciaj sia thiab lub neej zoo ntawm cov neeg mob nrog PAAD.
Qhov kev pom tsis zoo ntawm PAAD feem ntau yog los ntawm kev tiv thaiv cov tshuaj khomob.Nyob rau xyoo tas los no, cov tshuaj tiv thaiv kab mob tiv thaiv kab mob tau siv dav hauv kev kho cov qog nqaij hlav [8].Txawm li cas los xij, kev siv ICIs hauv kev mob qog nqaij hlav pancreatic tsis tshua muaj kev vam meej [9].Yog li ntawd, nws yog ib qho tseem ceeb los txheeb xyuas cov neeg mob uas yuav tau txais txiaj ntsig los ntawm kev kho ICI.
Ntev tsis-coding RNA (lncRNA) yog hom tsis-coding RNA nrog cov ntawv sau tseg> 200 nucleotides.LncRNAs yog dav thiab muaj li ntawm 80% ntawm tib neeg transcriptome [10].Lub cev loj ntawm kev ua haujlwm tau pom tias lncRNA-based prognostic qauv tuaj yeem kwv yees tus neeg mob tau zoo [11, 12].Piv txwv li, 18 autophagy-related lncRNAs tau txheeb xyuas los tsim cov cim prognostic hauv mob qog noj ntshav [13].Rau lwm yam kev tiv thaiv kab mob lncRNAs tau raug siv los tsim kom muaj cov yam ntxwv ntawm glioma [14].
Hauv kev mob qog noj ntshav pancreatic, qee qhov kev tshawb fawb tau tsim LncRNA-raws li kos npe los kwv yees tus neeg mob.Daim ntawv kos npe 3-lncRNA tau tsim nyob rau hauv pancreatic adenocarcinoma nrog thaj tsam hauv qab ROC nkhaus (AUC) tsuas yog 0.742 thiab tag nrho cov ciaj sia taus (OS) ntawm 3 xyoos [15].Tsis tas li ntawd, lncRNA qhia qhov tseem ceeb sib txawv ntawm cov genomes sib txawv, cov ntaub ntawv sib txawv, thiab cov neeg mob sib txawv, thiab qhov ua tau zoo ntawm cov qauv kev kwv yees tsis ruaj khov.Yog li ntawd, peb siv cov qauv tshiab algorithm, kev sib koom ua ke thiab iteration, los tsim kev tiv thaiv kab mob ntsig txog lncRNA (irlncRNA) kos npe los tsim cov qauv kev kwv yees ntau dua thiab ruaj khov [8].
Normalized RNAseq cov ntaub ntawv (FPKM) thiab kev kho mob qog noj ntshav pancreatic TCGA thiab genotype cov ntaub so ntswg qhia (GTEx) cov ntaub ntawv tau txais los ntawm UCSC XENA database ( https://xenabrowser.net/datapages/ ).GTF cov ntaub ntawv tau txais los ntawm Ensembl database ( http://asia.ensembl.org ) thiab siv los rho tawm lncRNA qhia profiles los ntawm RNAseq.Peb rub tawm cov tshuaj tiv thaiv kab mob los ntawm ImmPort database (http://www.immport.org) thiab txheeb xyuas kev tiv thaiv kab mob ntsig txog lncRNAs (irlncRNAs) siv kev txheeb xyuas kev sib raug zoo (p <0.001, r> 0.4).Kev txheeb xyuas qhov sib txawv ntawm irlncRNAs (DEirlncRNAs) los ntawm kev hla irlncRNAs thiab sib txawv qhia lncRNAs tau los ntawm GEPIA2 database (http://gepia2.cancer-pku.cn/#index) hauv TCGA-PAAD cohort (|logFC| > 1 thiab FDR <0.05).
Txoj kev no tau tshaj tawm yav dhau los [8].Tshwj xeeb, peb tsim X los hloov cov khub lncRNA A thiab lncRNA B. Thaum cov lus qhia tus nqi ntawm lncRNA A siab dua qhov qhia tus nqi ntawm lncRNA B, X txhais tau tias yog 1, txwv tsis pub X txhais tau tias yog 0. Yog li ntawd, peb tuaj yeem tau txais ib tug matrix ntawm 0 los yog – 1. Lub ntsug axis ntawm lub matrix sawv cev rau txhua tus qauv, thiab kab rov tav axis sawv cev rau txhua DEirlncRNA khub nrog tus nqi ntawm 0 los yog 1.
Univariate regression tsom xam ua raws li Lasso regression tau siv los tshuaj xyuas cov DEirlncRNA khub.Lub lasso regression tsom xam siv 10-fold cross-validation rov 1000 zaug (p <0.05), nrog 1000 random stimuli ib khiav.Thaum qhov zaus ntawm txhua DEirlncRNA khub tau tshaj 100 zaug hauv 1000 lub voj voog, DEirlncRNA khub tau raug xaiv los tsim cov qauv kev pheej hmoo.Tom qab ntawd peb tau siv AUC nkhaus los nrhiav qhov kev txiav tawm zoo tshaj plaws rau kev faib cov neeg mob PAAD rau hauv pawg siab thiab tsis tshua muaj kev pheej hmoo.Tus nqi AUC ntawm txhua tus qauv kuj tau suav thiab npaj ua qhov nkhaus.Yog tias qhov nkhaus nce mus txog qhov siab tshaj plaws uas qhia txog qhov siab tshaj plaws AUC tus nqi, cov txheej txheem suav yuav tsum nres thiab tus qauv suav tias yog tus neeg sib tw zoo tshaj plaws.1-, 3- thiab 5-xyoo ROC nkhaus qauv tau tsim.Univariate thiab multivariate regression tsom xam tau siv los tshuaj xyuas qhov kev ua tau zoo ntawm kev kwv yees ntawm tus qauv kev pheej hmoo.
Siv xya lub cuab yeej los kawm txog kev tiv thaiv kab mob hauv lub cev, suav nrog XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, thiab CIBERSORT.Immune cell infiltration data tau rub tawm los ntawm TIMER2 database (http://timer.comp-genomics.org/#tab-5817-3).Qhov sib txawv ntawm cov ntsiab lus ntawm lub cev tiv thaiv kab mob hauv nruab nrab ntawm cov pab pawg siab- thiab tsis tshua muaj kev pheej hmoo ntawm cov qauv tsim tau raug tshuaj xyuas siv Wilcoxon kos npe-qib xeem, cov txiaj ntsig tau pom hauv daim duab square.Spearman correlation tsom xam tau ua los tshuaj xyuas qhov kev sib raug zoo ntawm cov qhab nia ntawm qhov kev pheej hmoo thiab cov kab mob tiv thaiv kab mob.Qhov txiaj ntsig kev sib raug zoo coefficient yog qhia raws li lollipop.Qhov ntsuas qhov tseem ceeb tau teeb tsa ntawm p <0.05.Cov txheej txheem tau ua tiav siv R pob ggplot2.Txhawm rau tshuaj xyuas qhov kev sib raug zoo ntawm tus qauv thiab cov qib qhia cov noob cuam tshuam nrog kev tiv thaiv kab mob hauv lub cev, peb tau ua ggstatslot pob thiab violin zaj duab xis pom.
Txhawm rau ntsuas cov qauv kev kho mob rau kev mob qog noj ntshav pancreatic, peb suav IC50 ntawm cov tshuaj siv tshuaj khomob feem ntau hauv TCGA-PAAD pawg.Qhov sib txawv ntawm ib nrab inhibitory concentrations (IC50) ntawm cov pab pawg siab thiab tsis tshua muaj kev pheej hmoo raug muab piv nrog Wilcoxon kos npe-qib xeem, thiab cov txiaj ntsig tau pom tias yog lub thawv ntawv tsim los siv pRRophetic thiab ggplot2 hauv R. Txhua txoj hauv kev ua raws li cov lus qhia thiab cov qauv.
Kev ua haujlwm ntawm peb txoj kev tshawb fawb tau pom nyob rau hauv daim duab 1. Siv kev txheeb xyuas kev sib raug zoo ntawm lncRNAs thiab kev tiv thaiv kab mob ntsig txog cov noob, peb xaiv 724 irlncRNAs nrog p <0.01 thiab r> 0.4.Peb tom ntej no tau txheeb xyuas qhov sib txawv ntawm lncRNAs ntawm GEPIA2 (Daim duab 2A).Tag nrho ntawm 223 irlncRNAs tau qhia txawv ntawm pancreatic adenocarcinoma thiab cov ntaub so ntswg ntawm tus txiav (|logFC| > 1, FDR < 0.05), hu ua DEirlncRNAs.
Kev tsim kho ntawm cov qauv kev pheej hmoo.(A) Volcano zaj duab xis ntawm qhov sib txawv qhia lncRNAs.(B) Kev faib tawm ntawm lasso coefficients rau 20 DEirlncRNA khub.(C) Ib feem yuav muaj qhov sib txawv ntawm LASSO coefficient faib.(D) Cov phiaj xwm hav zoov uas qhia txog kev txheeb xyuas qhov tsis sib xws ntawm 20 DEirlncRNA khub.
Peb txuas ntxiv tsim ib qho 0 lossis 1 matrix los ntawm kev sib koom ua ke 223 DEirlncRNAs.Tag nrho ntawm 13,687 DEirlncRNA khub tau txheeb xyuas.Tom qab univariate thiab lasso regression tsom xam, 20 DEirlncRNA khub thaum kawg tau sim los tsim tus qauv kev pheej hmoo (Daim duab 2B-D).Raws li cov txiaj ntsig ntawm Lasso thiab ntau qhov kev ntsuam xyuas rov qab, peb suav cov qhab nia txaus ntshai rau txhua tus neeg mob hauv TCGA-PAAD pawg (Table 1).Raws li cov txiaj ntsig ntawm lasso regression tsom xam, peb suav cov qhab nia txaus ntshai rau txhua tus neeg mob hauv TCGA-PAAD pawg.AUC ntawm ROC nkhaus yog 0.905 rau 1-xyoo kev pheej hmoo tus qauv kwv yees, 0.942 rau 2-xyoo kev kwv yees, thiab 0.966 rau 3-xyoo kev kwv yees (Daim duab 3A-B).Peb tau teeb tsa qhov kev txiav tawm zoo tshaj plaws ntawm 3.105, stratified TCGA-PAAD pawg neeg mob rau hauv cov pab pawg siab thiab tsis tshua muaj kev pheej hmoo, thiab npaj cov txiaj ntsig ntawm kev ciaj sia thiab cov qhab nia raug faib rau txhua tus neeg mob (Daim duab 3C-E).Kaplan-Meier tsom xam pom tias kev ciaj sia ntawm PAAD cov neeg mob nyob rau hauv pab pawg neeg muaj kev pheej hmoo siab tau qis dua li cov neeg mob hauv pab pawg uas muaj kev pheej hmoo tsawg (p <0.001) (Daim duab 3F).
Kev siv tau ntawm cov qauv kev pheej hmoo prognostic.(A) ROC ntawm cov qauv kev pheej hmoo.(B) 1-, 2-, thiab 3-xyoo ROC prognostic kev pheej hmoo qauv.(C) ROC ntawm prognostic risk model.Qhia qhov pom kev txiav-tawm taw tes.(DE) Kev faib tawm ntawm kev muaj sia nyob (D) thiab cov qhab nia txaus ntshai (E).(F) Kev tshuaj xyuas Kaplan-Meier ntawm PAAD cov neeg mob hauv cov pab pawg muaj kev pheej hmoo siab thiab qis.
Peb txuas ntxiv ntsuas qhov sib txawv ntawm cov qhab nia txaus ntshai los ntawm cov yam ntxwv kho mob.Daim duab 4A (Daim duab 4A) qhia tag nrho kev sib raug zoo ntawm cov yam ntxwv kho mob thiab cov qhab nia txaus ntshai.Tshwj xeeb, cov neeg mob laus muaj cov qhab nias siab dua (Daim duab 4B).Tsis tas li ntawd, cov neeg mob uas muaj theem II muaj kev pheej hmoo siab dua li cov neeg mob uas muaj theem I (Daim duab 4C).Hais txog qib qog nqaij hlav hauv cov neeg mob PAAD, qib 3 cov neeg mob tau muaj kev pheej hmoo siab dua cov neeg mob qib 1 thiab 2 (Daim duab 4D).Peb tau ua qhov kev soj ntsuam univariate thiab multivariate regression thiab ua pov thawj tias qhov kev pheej hmoo (p < 0.001) thiab hnub nyoog (p = 0.045) yog cov kev tshawb fawb ywj pheej hauv cov neeg mob PAAD (Daim duab 5A-B).ROC nkhaus tau pom tias qhov kev pheej hmoo siab dua rau lwm yam kev kho mob hauv kev kwv yees 1-, 2-, thiab 3-xyoo txoj sia nyob ntawm cov neeg mob PAAD (Daim duab 5C-E).
Cov yam ntxwv kho mob ntawm cov qauv kev pheej hmoo prognostic.Histogram (A) qhia (B) hnub nyoog, (C) qog theem, (D) qib qog, cov qhab nia txaus ntshai, thiab poj niam txiv neej ntawm cov neeg mob hauv pawg TCGA-PAAD.** p <0.01
Independent kwv yees tsom xam ntawm prognostic txaus ntshai qauv.(AB) Univariate (A) thiab multivariate (B) regression tsom xam ntawm cov qauv kev pheej hmoo thiab cov yam ntxwv kho mob.(CE) 1-, 2-, thiab 3-xyoo ROC rau cov qauv kev pheej hmoo thiab cov yam ntxwv kho mob
Yog li ntawd, peb tau tshuaj xyuas qhov kev sib raug zoo ntawm lub sijhawm thiab cov qhab nia txaus ntshai.Peb pom tias cov qhab nia txaus ntshai hauv PAAD cov neeg mob tau sib cuam tshuam nrog CD8 + T hlwb thiab NK hlwb (Daim duab 6A), qhia txog kev tiv thaiv kab mob hauv cov pab pawg muaj kev pheej hmoo siab.Peb kuj tau soj ntsuam qhov sib txawv ntawm kev tiv thaiv kab mob hauv lub cev ntawm cov pab pawg siab thiab tsis tshua muaj kev pheej hmoo thiab pom cov txiaj ntsig zoo ib yam (Daim duab 7).Muaj tsawg infiltration ntawm CD8 + T hlwb thiab NK hlwb nyob rau hauv cov pab pawg neeg muaj kev pheej hmoo siab.Hauv xyoo tas los no, cov tshuaj tiv thaiv kab mob tiv thaiv kab mob (ICIs) tau siv dav hauv kev kho cov qog nqaij hlav.Txawm li cas los xij, kev siv ICIs hauv kev mob qog nqaij hlav pancreatic tsis tshua muaj kev vam meej.Yog li ntawd, peb tau soj ntsuam qhov kev qhia ntawm cov tshuaj tiv thaiv kab mob hauv cov pab pawg uas muaj kev pheej hmoo siab thiab qis.Peb pom tias CTLA-4 thiab CD161 (KLRB1) tau nthuav tawm ntau dhau hauv pawg uas muaj kev pheej hmoo tsawg (Daim duab 6B-G), qhia tias cov neeg mob PAAD hauv pawg tsis tshua muaj kev pheej hmoo yuav raug cuam tshuam rau ICI.
Kev txheeb xyuas qhov kev pheej hmoo ntawm tus qauv prognostic thiab kev tiv thaiv kab mob hauv lub cev.(A) Kev sib raug zoo ntawm cov qauv kev pheej hmoo thiab kev tiv thaiv kab mob hauv lub cev.(BG) Qhia txog noob caj noob ces nyob rau hauv cov pab pawg siab thiab tsis tshua muaj kev pheej hmoo.(HK) IC50 qhov tseem ceeb rau cov tshuaj tiv thaiv kab mob tshwj xeeb hauv cov pab pawg siab thiab qis.*p <0.05, **p <0.01, ns = tsis tseem ceeb
Peb tau soj ntsuam ntxiv txog kev sib koom ua ke ntawm cov qhab nia txaus ntshai thiab cov kws kho mob siv tshuaj kho mob hauv TCGA-PAAD pawg.Peb tau tshawb nrhiav cov tshuaj tiv thaiv kabmob kheesxaws feem ntau hauv kev mob qog noj ntshav pancreatic thiab tshuaj xyuas qhov sib txawv ntawm lawv cov IC50 qhov tseem ceeb ntawm pawg siab- thiab qis.Cov txiaj ntsig tau pom tias IC50 tus nqi ntawm AZD.2281 (olaparib) yog siab dua nyob rau hauv pawg neeg muaj kev pheej hmoo siab, qhia tias PAAD cov neeg mob hauv pawg neeg muaj kev pheej hmoo siab tuaj yeem tiv taus AZD.2281 kev kho mob (Daim duab 6H).Tsis tas li ntawd, IC50 qhov tseem ceeb ntawm paclitaxel, sorafenib, thiab erlotinib tau qis dua hauv pawg uas muaj kev pheej hmoo siab (Daim duab 6I-K).Peb tau txheeb xyuas ntxiv 34 cov tshuaj tiv thaiv kab mob cancer nrog cov txiaj ntsig IC50 siab dua hauv pab pawg muaj kev pheej hmoo siab thiab 34 cov tshuaj tiv thaiv kab mob nrog qis IC50 qhov tseem ceeb hauv pab pawg muaj kev pheej hmoo siab (Table 2).
Nws tsis tuaj yeem tsis lees paub tias lncRNAs, mRNAs, thiab miRNAs dav muaj nyob thiab ua lub luag haujlwm tseem ceeb hauv kev txhim kho qog noj ntshav.Muaj cov pov thawj txaus txhawb nqa lub luag haujlwm tseem ceeb ntawm mRNA lossis miRNA hauv kev kwv yees kev ciaj sia nyob hauv ntau hom mob qog noj ntshav.Undoubtedly, ntau cov qauv kev pheej hmoo pheej hmoo kuj yog raws li lncRNAs.Piv txwv li, Luo et al.Cov kev tshawb fawb tau pom tias LINC01094 plays lub luag haujlwm tseem ceeb hauv PC proliferation thiab metastasis, thiab kev qhia siab ntawm LINC01094 qhia tias muaj sia nyob tsis zoo ntawm cov neeg mob qog nqaij hlav pancreatic [16].Txoj kev tshawb no nthuav tawm los ntawm Lin et al.Cov kev tshawb fawb tau pom tias kev txo qis ntawm lncRNA FLVCR1-AS1 cuam tshuam nrog kev ua haujlwm tsis zoo hauv cov neeg mob qog noj ntshav pancreatic [17].Txawm li cas los xij, kev tiv thaiv kab mob ntsig txog lncRNAs yog qhov sib tham tsawg dua los ntawm kev kwv yees kev ciaj sia tag nrho ntawm cov neeg mob qog noj ntshav.Tsis ntev los no, ntau txoj haujlwm tau tsom mus rau kev tsim cov qauv kev pheej hmoo los kwv yees txoj sia nyob ntawm cov neeg mob qog noj ntshav thiab yog li kho cov kev kho mob [18, 19, 20].Muaj kev paub txog lub luag haujlwm tseem ceeb ntawm kev tiv thaiv kab mob infiltrates hauv kev pib mob qog noj ntshav, kev loj hlob, thiab kev teb rau cov kev kho mob xws li kws khomob.Ntau cov kev tshawb fawb tau lees paub tias cov qog-infiltrating lub cev tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev teb rau cytotoxic chemotherapy [21, 22, 23].Cov qog tiv thaiv kab mob microenvironment yog qhov tseem ceeb hauv kev ciaj sia ntawm cov neeg mob qog [24, 25].Immunotherapy, tshwj xeeb tshaj yog kev kho ICI, yog siv dav hauv kev kho mob qog nqaij hlav [26].Cov kab mob tiv thaiv kab mob tau siv dav los tsim cov qauv kev pheej hmoo.Piv txwv li, Su et al.Tus qauv tiv thaiv kab mob tiv thaiv kev pheej hmoo yog raws li cov protein-coding genes los kwv yees qhov tshwm sim ntawm cov neeg mob qog noj ntshav zes qe menyuam [27].Cov noob tsis-coding xws li lncRNAs kuj tsim nyog rau kev tsim cov qauv kev pheej hmoo [28, 29, 30].Luo et al tau sim plaub lub cev tiv thaiv kab mob lncRNAs thiab tsim cov qauv kev kwv yees rau kev pheej hmoo mob qog noj ntshav [31].Khan et al.Tag nrho ntawm 32 qhov sib txawv ntawm cov ntawv sau tau raug txheeb xyuas, thiab raws li qhov no, tus qauv kwv yees nrog 5 cov ntawv teev lus tseem ceeb tau tsim, uas tau npaj los ua ib qho cuab yeej pom zoo rau kev kwv yees biopsy-proven acute rejection tom qab hloov lub raum [32].
Feem ntau ntawm cov qauv no yog ua raws li qib kev qhia gene, xws li protein-coding genes lossis non-coding genes.Txawm li cas los xij, tib lub noob tuaj yeem muaj qhov sib txawv ntawm qhov sib txawv hauv cov genomes sib txawv, cov ntaub ntawv tawm tswv yim thiab hauv cov neeg mob sib txawv, ua rau cov kev kwv yees tsis ruaj khov hauv cov qauv kev kwv yees.Hauv txoj kev tshawb no, peb tau tsim ib qho qauv tsim nyog nrog ob khub ntawm lncRNAs, ywj siab ntawm qhov tseeb qhia qhov tseem ceeb.
Hauv txoj kev tshawb no, peb tau txheeb xyuas irlncRNA thawj zaug los ntawm kev txheeb xyuas kev sib raug zoo nrog cov noob caj noob ces.Peb tau tshuaj xyuas 223 DEirlncRNAs los ntawm hybridization nrog qhov sib txawv ntawm lncRNAs.Qhov thib ob, peb tsim 0-los-1 matrix raws li luam tawm DEirlncRNA khub txoj kev [31].Tom qab ntawd peb tau ua qhov kev ntsuam xyuas kev tsis sib haum xeeb thiab lasso regression los txheeb xyuas cov khub DEirlncRNA thiab tsim cov qauv kev pheej hmoo.Peb tau soj ntsuam ntxiv txog kev sib koom ua ke ntawm cov qhab nia txaus ntshai thiab cov yam ntxwv kho mob hauv cov neeg mob PAAD.Peb pom tias peb cov qauv kev pheej hmoo pheej hmoo, raws li qhov muaj txiaj ntsig zoo hauv cov neeg mob PAAD, tuaj yeem sib txawv cov neeg mob qib siab los ntawm cov neeg mob qis thiab cov neeg mob qib siab los ntawm cov neeg mob qis.Tsis tas li ntawd, AUC qhov tseem ceeb ntawm ROC nkhaus ntawm tus qauv prognostic txaus ntshai yog 0.905 rau 1-xyoo kev kwv yees, 0.942 rau 2-xyoo kev kwv yees, thiab 0.966 rau 3-xyoo kev kwv yees.
Cov kws tshawb fawb tau tshaj tawm tias cov neeg mob uas muaj CD8 + T cell infiltration ntau dua rau kev kho ICI [33].Kev nce hauv cov ntsiab lus ntawm cytotoxic cells, CD56 NK hlwb, NK hlwb thiab CD8+ T hlwb hauv cov qog tiv thaiv kab mob microenvironment tej zaum yuav yog ib qho ntawm cov laj thawj rau cov qog nqaij hlav ua haujlwm [34].Cov kev tshawb fawb yav dhau los tau pom tias qib siab ntawm cov qog-infiltrating CD4(+) T thiab CD8(+) T tau cuam tshuam nrog kev muaj sia nyob ntev [35].Tsis zoo CD8 T cell infiltration, tsis tshua muaj neoantigen load, thiab ib tug heev immunosuppressive qog microenvironment ua rau tsis muaj lus teb rau ICI txoj kev kho [36].Peb pom tias cov qhab-nees txaus ntshai tau cuam tshuam tsis zoo nrog CD8 + T hlwb thiab NK hlwb, qhia tias cov neeg mob uas muaj cov qhab nia siab yuav tsis haum rau kev kho ICI thiab muaj qhov tshwm sim tsis zoo.
CD161 yog ib qho cim ntawm natural killer (NK) hlwb.CD8 + CD161+ CAR-transduced T hlwb kho kom zoo dua hauv vivo antitumor kev ua tau zoo hauv HER2+ pancreatic ductal adenocarcinoma xenograft qauv [37].Immune checkpoint inhibitors tsom cytotoxic T lymphocyte txuam protein 4 (CTLA-4) thiab programmed cell tuag protein 1 (PD-1) / programmed cell tuag ligand 1 (PD-L1) txoj hauv kev thiab muaj peev xwm loj hauv ntau thaj chaw.Kev nthuav qhia ntawm CTLA-4 thiab CD161 (KLRB1) qis dua hauv cov pab pawg muaj kev pheej hmoo siab, qhia ntxiv tias cov neeg mob uas muaj cov qhab nia txaus ntshai yuav tsis tsim nyog rau kev kho mob ICI.[38]
Txhawm rau nrhiav kev kho mob tsim nyog rau cov neeg mob uas muaj kev pheej hmoo siab, peb tau txheeb xyuas ntau yam tshuaj tiv thaiv kab mob thiab pom tias paclitaxel, sorafenib, thiab erlotinib, uas tau siv dav hauv cov neeg mob PAAD, yuav tsim nyog rau cov neeg mob uas muaj kev pheej hmoo siab nrog PAAD.[33].Zhang et al pom tias kev hloov pauv hauv ib qho kev puas tsuaj DNA (DDR) txoj hauv kev tuaj yeem ua rau tsis zoo rau cov neeg mob qog noj ntshav prostate [39].Pancreatic Cancer Olaparib Ongoing (POLO) kev sim tau pom tias kev kho mob nrog olaparib ncua ntev tsis muaj sia nyob piv nrog cov placebo tom qab thawj kab platinum-based chemotherapy hauv cov neeg mob pancreatic ductal adenocarcinoma thiab germline BRCA1/2 mutations [40].Qhov no muab kev cia siab tseem ceeb tias cov txiaj ntsig kev kho mob yuav txhim kho tau zoo hauv pawg neeg mob no.Nyob rau hauv txoj kev tshawb no, IC50 tus nqi ntawm AZD.2281 (olaparib) yog siab dua nyob rau hauv pawg neeg muaj kev pheej hmoo siab, qhia tias PAAD cov neeg mob nyob rau hauv pab pawg neeg muaj kev pheej hmoo siab tuaj yeem tiv taus kev kho mob nrog AZD.2281.
Cov qauv kev kwv yees hauv qhov kev tshawb fawb no tsim cov txiaj ntsig zoo, tab sis lawv yog raws li kev kwv yees kwv yees.Yuav ua li cas kom paub meej cov txiaj ntsig no nrog cov ntaub ntawv kho mob yog ib lo lus nug tseem ceeb.Endoscopic fine needle aspiration ultrasonography (EUS-FNA) tau dhau los ua ib txoj hauv kev tseem ceeb rau kev kuaj xyuas cov kab mob pancreatic thiab extrapancreatic rhiab heev ntawm 85% thiab qhov tshwj xeeb ntawm 98% [41].Kev tshwm sim ntawm EUS fine-needle biopsy (EUS-FNB) koob yog tsuas yog raws li kev pom zoo ntawm FNA, xws li kev kuaj mob ntau dua, tau txais cov qauv uas khaws cov qauv histological, thiab yog li tsim cov ntaub so ntswg tiv thaiv kab mob uas tseem ceeb rau qee yam kev kuaj mob.stains tshwj xeeb [42].Kev tshuaj xyuas zoo ntawm cov ntaub ntawv tau lees paub tias FNB koob (tshwj xeeb tshaj yog 22G) ua kom pom qhov ua tau zoo tshaj plaws hauv kev sau cov ntaub so ntswg los ntawm pancreatic masses [43].Clinically, tsuas yog ib tug me me ntawm cov neeg mob tau txais kev phais radical, thiab feem ntau cov neeg mob muaj cov qog ua haujlwm tsis tau thaum lub sijhawm kuaj thawj zaug.Hauv kev xyaum kho mob, tsuas yog ib feem me me ntawm cov neeg mob uas tsim nyog rau kev phais radical vim tias feem ntau cov neeg mob muaj cov qog ua haujlwm tsis tau thaum lub sijhawm kuaj pom thawj zaug.Tom qab kev pom zoo pathological los ntawm EUS-FNB thiab lwm txoj hauv kev, kev kho mob tsis yog phais xws li tshuaj tua kab mob feem ntau yog xaiv.Peb qhov kev tshawb fawb tom ntej no yog los sim cov qauv prognostic ntawm txoj kev tshawb no hauv kev phais thiab tsis yog phais los ntawm kev tshuaj xyuas rov qab.
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Post lub sij hawm: Sep-22-2023