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