Khansara ya Pancreatic ndi imodzi mwazotupa zakupha kwambiri padziko lonse lapansi zomwe sizikudziwika bwino.Chifukwa chake, njira yolosera yolondola ndiyofunikira kuti muzindikire odwala omwe ali pachiwopsezo chachikulu cha khansa ya kapamba kuti agwirizane ndi chithandizo ndikuwongolera momwe odwalawa amathandizira.
Tidapeza data ya Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq kuchokera ku database ya UCSC Xena, tidazindikira ma lncRNAs (irlncRNAs) okhudzana ndi chitetezo chamthupi kudzera pakuwunika kolumikizana, ndikuzindikira kusiyana pakati pa TCGA ndi minyewa wamba ya pancreatic adenocarcinoma.DEirlncRNA) kuchokera ku TCGA ndi genotype tissue expression (GTEx) ya pancreatic minofu.Kusanthula kwina kosasinthika ndi lasso regression kunachitika kuti apange ma signature amtsogolo.Kenako tidawerengera dera lomwe lili pansi pa phirilo ndikuzindikira mtengo wofunikira kwambiri wodziwira odwala omwe ali ndi chiopsezo chachikulu komanso chochepa chapancreatic adenocarcinoma.Kuyerekeza mawonekedwe achipatala, kulowetsedwa kwa maselo a chitetezo chamthupi, immunosuppressive microenvironment, ndi chemotherapy resistance kwa odwala omwe ali ndi khansa yapang'onopang'ono kwambiri komanso yochepa.
Tidazindikira awiriawiri a DEirlncRNA 20 ndikuyika odwala m'magulu molingana ndi mtengo wocheperako.Tidawonetsa kuti mawonekedwe athu osayina ali ndi ntchito yayikulu pakulosera zam'tsogolo za odwala omwe ali ndi PAAD.AUC yokhotakhota ya ROC ndi 0.905 pazolosera za chaka chimodzi, 0.942 pazaka ziwiri zamtsogolo, ndi 0.966 pazolosera zazaka zitatu.Odwala omwe ali pachiwopsezo chachikulu anali ndi moyo wocheperako komanso mawonekedwe oipitsitsa azachipatala.Tidawonetsanso kuti odwala omwe ali pachiwopsezo chachikulu amakhala ndi immunosuppressed ndipo amatha kukana immunotherapy.Kuwunika kwa mankhwala oletsa khansa monga paclitaxel, sorafenib, ndi erlotinib pogwiritsa ntchito zida zolosera zamakompyuta kungakhale koyenera kwa odwala omwe ali pachiopsezo chachikulu cha PAAD.
Ponseponse, kafukufuku wathu adakhazikitsa njira yatsopano yopangira chiwopsezo chotengera irlncRNA, yomwe idawonetsa kudalirika kwa odwala omwe ali ndi khansa ya kapamba.Chitsanzo chathu chowopsa chingathandize kusiyanitsa odwala omwe ali ndi PAAD omwe ali oyenera kulandira chithandizo chamankhwala.
Khansara ya Pancreatic ndi chotupa chowopsa chomwe chimakhala ndi moyo wocheperako zaka zisanu komanso kalasi yapamwamba.Pa nthawi ya matenda, odwala ambiri ali kale patsogolo.Pankhani ya mliri wa COVID-19, madotolo ndi anamwino ali pamavuto akulu pochiza odwala khansa ya kapamba, ndipo mabanja a odwala nawonso amakumana ndi zovuta zingapo popanga zisankho zachipatala [1, 2].Ngakhale kupita patsogolo kwakukulu kwachitika pochiza ma DOAD, monga chithandizo cha neoadjuvant, opaleshoni ya opaleshoni, mankhwala opatsirana pogwiritsa ntchito ma radiation, chemotherapy, mankhwala opangidwa ndi maselo, ndi chitetezo cha mthupi (ICIs), pafupifupi 9% yokha ya odwala omwe amapulumuka zaka zisanu atazindikira [3] ].], 4].Chifukwa zizindikiro zoyamba za pancreatic adenocarcinoma ndizosawoneka bwino, odwala nthawi zambiri amapezeka kuti ali ndi metastases pamlingo wapamwamba [5].Choncho, kwa wodwala wopatsidwa, chithandizo chokwanira payekha payekha chiyenera kuyeza ubwino ndi kuipa kwa njira zonse zothandizira, osati kuti apitirize kukhala ndi moyo, komanso kuti akhale ndi moyo wabwino [6].Chifukwa chake, njira yolosera yothandiza ndiyofunikira kuti muwunikire molondola momwe wodwalayo alili [7].Choncho, chithandizo choyenera chingasankhidwe kuti chikhale ndi moyo wabwino komanso umoyo wa odwala omwe ali ndi PAAD.
Kusazindikira bwino kwa PAAD kumachitika makamaka chifukwa cha kukana mankhwala a chemotherapy.M'zaka zaposachedwa, ma immune checkpoint inhibitors akhala akugwiritsidwa ntchito kwambiri pochiza zotupa zolimba [8].Komabe, kugwiritsa ntchito ma ICI mu khansa ya kapamba sikupambana [9].Choncho, nkofunika kuzindikira odwala omwe angapindule ndi chithandizo cha ICI.
RNA yayitali yosalemba (lncRNA) ndi mtundu wa RNA yosalemba zolemba>200 nucleotides.LncRNAs ndizofala ndipo zimapanga pafupifupi 80% ya zolemba zamunthu [10].Ntchito yayikulu yawonetsa kuti zitsanzo zodziwikiratu za lncRNA zimatha kulosera zam'tsogolo za odwala [11, 12].Mwachitsanzo, ma 18 okhudzana ndi autophagy lncRNA adadziwika kuti apange ma signature a khansa ya m'mawere [13].Ma LncRNA ena asanu ndi limodzi okhudzana ndi chitetezo chamthupi agwiritsidwa ntchito kukhazikitsa mawonekedwe a glioma [14].
Mu khansa ya kapamba, kafukufuku wina wakhazikitsa siginecha zozikidwa pa lncRNA kuti zilosere zam'tsogolo za odwala.Siginecha ya 3-lncRNA idakhazikitsidwa mu pancreatic adenocarcinoma yokhala ndi malo pansi pa ROC curve (AUC) ya 0.742 yokha komanso kupulumuka kwathunthu (OS) kwa zaka 3 [15].Kuphatikiza apo, mafotokozedwe a lncRNA amasiyana pakati pa ma genome osiyanasiyana, mitundu yosiyanasiyana ya data, ndi odwala osiyanasiyana, ndipo machitidwe amomwe amalosera amakhala osakhazikika.Chifukwa chake, timagwiritsa ntchito buku lachitsanzo lachitsanzo, kuphatikizika ndi kubwereza, kuti tipange siginecha zokhudzana ndi chitetezo chamthupi cha lncRNA (irlncRNA) kuti tipange zolosera zolondola komanso zokhazikika [8].
Deta yamtundu wa RNAseq (FPKM) ndi khansa ya pancreatic TCGA ndi genotype tissue expression (GTEx) zinapezedwa kuchokera ku UCSC XENA database (https://xenabrowser.net/datapages/).Mafayilo a GTF adapezedwa kuchokera ku database ya Ensembl ( http://asia.ensembl.org ) ndipo adagwiritsidwa ntchito kuchotsa mbiri ya lncRNA kuchokera ku RNAseq.Tidatsitsa majini okhudzana ndi chitetezo chamthupi m'nkhokwe ya ImmPort (http://www.immport.org) ndi kuzindikira ma lncRNAs (irlncRNAs) okhudzana ndi chitetezo chamthupi pogwiritsa ntchito kusanthula kolumikizana (p <0.001, r > 0.4).Kuzindikiritsa ma irlncRNAs (DEirlncRNAs) podutsa ma irlncRNA ndi ma lncRNA owonetsedwa mosiyanasiyana omwe atengedwa kuchokera munkhokwe ya GEPIA2 (http://gepia2.cancer-pku.cn/#index) mu gulu la TCGA-PAAD (|logFC| > 1 ndi FDR <0.05).
Njirayi idanenedwa kale [8].Mwachindunji, timapanga X kuti tilowe m'malo mwa lncRNA A ndi lncRNA B. Pamene mtengo wa lncRNA A uli wapamwamba kusiyana ndi lncRNA B, X imatanthauzidwa ngati 1, mwinamwake X imatanthauzidwa ngati 0. Choncho, tikhoza kupeza matrix a 0 kapena - 1. Mzere wowongoka wa matrix umayimira chitsanzo chilichonse, ndipo chopingasa chopingasa chimayimira peyala iliyonse ya DEirlncRNA yokhala ndi mtengo wa 0 kapena 1.
Kusanthula kosasinthika kosinthika kotsatiridwa ndi Lasso regression kudagwiritsidwa ntchito kuwunikira awiriawiri a DEirlncRNA.Kusanthula kwa lasso regression kumagwiritsa ntchito 10-fold cross-validation mobwerezabwereza 1000 times (p <0.05), ndi 1000 zolimbikitsa mwadzidzidzi pa kuthamanga.Pamene mafupipafupi a gulu lililonse la DEirlncRNA adadutsa nthawi za 100 m'mizere ya 1000, awiriawiri a DEirlncRNA adasankhidwa kuti apange chitsanzo cha chiopsezo.Kenako tidagwiritsa ntchito curve ya AUC kuti tipeze mtengo wokwanira wodula odwala a PAAD m'magulu omwe ali pachiwopsezo chachikulu komanso chochepa.Mtengo wa AUC wa mtundu uliwonse udawerengedwanso ndikukonzedwa ngati ma curve.Ngati phirilo lifika pachimake chosonyeza kuchuluka kwa AUC, njira yowerengera imayima ndipo chitsanzocho chimatengedwa kuti ndichofunika kwambiri.1-, 3- ndi 5-year ROC curve zitsanzo zinamangidwa.Kusanthula kosasinthika komanso kosinthika kosiyanasiyana kudagwiritsidwa ntchito pofufuza zodziyimira pawokha zolosera zachitsanzo chachiwopsezo.
Gwiritsani ntchito zida zisanu ndi ziwiri kuti muphunzire kuchuluka kwa ma cell a chitetezo chamthupi, kuphatikiza XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, ndi CIBERSORT.Deta yolowetsa ma cell a chitetezo chamthupi idatsitsidwa kuchokera munkhokwe ya TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Kusiyana kwa zomwe zili m'maselo olowetsa chitetezo chamthupi pakati pa magulu omwe ali ndi chiopsezo chachikulu komanso chochepa cha chitsanzo chomangidwacho chinawunikidwa pogwiritsa ntchito mayeso olembedwa ndi Wilcoxon, zotsatira zake zikuwonetsedwa mu square graph.Kusanthula kwamalumikizidwe a Spearman kunachitika kuti aunike ubale womwe ulipo pakati pa ziwopsezo zachitetezo ndi ma cell omwe amalowa mthupi.Chotsatira cholumikizira chimawonetsedwa ngati lollipop.Kufunika kofunikira kudakhazikitsidwa pa p <0.05.Njirayi idachitidwa pogwiritsa ntchito phukusi la R ggplot2.Kuti tiwone mgwirizano pakati pa mawonekedwe ndi mawonekedwe a jini okhudzana ndi kuchuluka kwa chitetezo chamthupi, tinapanga phukusi la ggstatsplot ndi mawonekedwe a violin.
Kuti tiwone momwe angathandizire khansa ya kapamba, tidawerengera IC50 yamankhwala omwe amagwiritsidwa ntchito kwambiri pagulu la TCGA-PAAD.Kusiyanitsa kwa theka la inhibitory concentrations (IC50) pakati pa magulu omwe ali ndi chiopsezo chachikulu ndi otsika amafanizidwa pogwiritsa ntchito mayeso a Wilcoxon omwe amasaina, ndipo zotsatira zikuwonetsedwa ngati mabokosi opangidwa pogwiritsa ntchito pRrophetic ndi ggplot2 mu R. Njira zonse zimagwirizana ndi malangizo oyenerera ndi zikhalidwe.
Mayendedwe a kafukufuku wathu akuwonetsedwa mu Chithunzi 1. Pogwiritsa ntchito kusanthula kwa mgwirizano pakati pa lncRNA ndi majini okhudzana ndi chitetezo cha mthupi, tinasankha 724 irlncRNAs ndi p <0.01 ndi r> 0.4.Kenako tidasanthula ma lncRNA owonetsedwa mosiyanasiyana a GEPIA2 (Chithunzi 2A).Ma irlncRNA okwana 223 adawonetsedwa mosiyana pakati pa pancreatic adenocarcinoma ndi minyewa wamba ya kapamba (|logFC| > 1, FDR <0.05), otchedwa DEirlncRNAs.
Kupanga zitsanzo za chiopsezo cholosera.(A) Chiwembu cha Volcano cha ma LncRNA owonetsedwa mosiyanasiyana.(B) Kugawa kwa lasso coefficients kwa 20 DEirlncRNA awiriawiri.(C) Kusiyana kwapang'onopang'ono kwa kugawa kokwanira kwa LASSO.(D) Chiwembu cha nkhalango chowonetsa kusanthula kosasinthika kwamagulu 20 a DEirlncRNA.
Kenako tinapanga matrix 0 kapena 1 pophatikiza 223 DEirlncRNAs.Onse awiriawiri a DEirlncRNA 13,687 adadziwika.Pambuyo pa kusanthula kosasinthika ndi lasso regression, awiriawiri a 20 DEirlncRNA adayesedwa potsiriza kuti apange chitsanzo cha chiopsezo chodziwika bwino (Chithunzi 2B-D).Malingana ndi zotsatira za Lasso ndi kusanthula kambirimbiri, tinawerengera chiwerengero cha chiopsezo kwa wodwala aliyense mu gulu la TCGA-PAAD (Table 1).Kutengera zotsatira za kusanthula kwa lasso regression, tinawerengera chiwopsezo cha wodwala aliyense mu gulu la TCGA-PAAD.AUC ya ROC yokhotakhota inali 0.905 ya 1 chaka cholosera zachiwopsezo, 0.942 pakulosera kwazaka 2, ndi 0.966 pakulosera kwazaka 3 (Chithunzi 3A-B).Tinakhazikitsa mtengo wabwino kwambiri wa 3.105, tinagwirizanitsa odwala a TCGA-PAAD m'magulu omwe ali pachiopsezo chachikulu komanso chochepa, ndipo tinakonza zotsatira za kupulumuka ndi kugawidwa kwa chiopsezo kwa wodwala aliyense (Chithunzi 3C-E).Kusanthula kwa Kaplan-Meier kunasonyeza kuti kupulumuka kwa odwala a PAAD m'gulu lachiwopsezo chachikulu kunali kochepa kwambiri kusiyana ndi odwala omwe ali m'gulu lochepa (p <0.001) (Chithunzi 3F).
Kutsimikizika kwa zitsanzo zachiwopsezo chamtsogolo.(A) ROC yachitsanzo chowopsa.(B) 1-, 2-, ndi 3-year ROC prognostic risk zitsanzo.(C) ROC yachitsanzo chowopsa.Imawonetsa malo abwino odulirapo.(DE) Kugawidwa kwa chikhalidwe cha kupulumuka (D) ndi zotsatira zoopsa (E).(F) Kusanthula kwa Kaplan-Meier kwa odwala PAAD m'magulu omwe ali ndi chiopsezo chachikulu komanso chochepa.
Tinayesanso kusiyana kwa ziwopsezo ndi mawonekedwe azachipatala.Chiwembu chojambula (Chithunzi 4A) chikuwonetsa ubale wonse pakati pa mawonekedwe azachipatala ndi ziwopsezo.Makamaka, odwala okalamba anali ndi chiopsezo chachikulu (Chithunzi 4B).Kuphatikiza apo, odwala omwe ali ndi siteji yachiwiri anali ndi chiopsezo chachikulu kuposa odwala omwe ali ndi siteji yoyamba (Chithunzi 4C).Ponena za kalasi ya chotupa mu odwala a PAAD, odwala a grade 3 anali ndi chiopsezo chachikulu kuposa odwala 1 ndi 2 odwala (Chithunzi 4D).Tidapitilizanso kusanthula kwaunivariate ndi ma multivariate regression ndikuwonetsa kuti kuchuluka kwachiwopsezo (p <0.001) ndi zaka (p = 0.045) zinali zodziyimira pawokha mwa odwala omwe ali ndi PAAD (Chithunzi 5A-B).Mphepete mwa ROC inasonyeza kuti chiwerengero cha chiopsezo chinali choposa zizindikiro zina zachipatala polosera za 1-, 2-, ndi zaka 3 za kupulumuka kwa odwala omwe ali ndi PAAD (Chithunzi 5C-E).
Makhalidwe azachipatala a zitsanzo zowopsa.Histogram (A) imawonetsa (B) zaka, (C) siteji ya chotupa, (D) chotupa, kuchuluka kwa chiopsezo, komanso jenda la odwala omwe ali mu gulu la TCGA-PAAD.**p <0.01
Kusanthula kodziyimira pawokha kwa zitsanzo zowopsa zamtsogolo.(AB) Univariate (A) ndi multivariate (B) regression regression of prognostic risk models and clinical characters.(CE) 1-, 2-, ndi 3-year ROC ya zitsanzo zachiwopsezo komanso mawonekedwe azachipatala
Chifukwa chake, tidasanthula ubale pakati pa nthawi ndi ziwopsezo.Tinapeza kuti chiwerengero cha chiopsezo cha odwala PAAD chinali chosagwirizana ndi CD8 + T maselo ndi NK maselo (Chithunzi 6A), kusonyeza kuponderezedwa kwa chitetezo cha mthupi m'gulu lachiwopsezo chachikulu.Tinayesanso kusiyana kwa kulowetsedwa kwa maselo a chitetezo cha mthupi pakati pa magulu omwe ali ndi chiopsezo chachikulu komanso chochepa ndipo tinapeza zotsatira zomwezo (Chithunzi 7).Panali kulowetsedwa kochepa kwa maselo a CD8 + T ndi maselo a NK mu gulu lachiopsezo chachikulu.M'zaka zaposachedwa, ma immune checkpoint inhibitors (ICIs) akhala akugwiritsidwa ntchito kwambiri pochiza zotupa zolimba.Komabe, kugwiritsa ntchito ma ICI mu khansa ya pancreatic sikunapambane.Chifukwa chake, tidawunika mawonekedwe amtundu wa chitetezo chamthupi m'magulu omwe ali pachiwopsezo chachikulu komanso chochepa.Tinapeza kuti CTLA-4 ndi CD161 (KLRB1) anali okhudzidwa kwambiri m'gulu lachiopsezo chochepa (Chithunzi 6B-G), kusonyeza kuti odwala PAAD omwe ali m'gulu lachiwopsezo chochepa akhoza kukhala okhudzidwa ndi ICI.
Kusanthula kolumikizana kwachitsanzo chachiwopsezo chamtsogolo komanso kulowa kwa chitetezo chamthupi.(A) Mgwirizano pakati pa chiwopsezo chamtsogolo komanso kulowa kwa chitetezo chamthupi.(BG) Imawonetsa mawonekedwe a jini m'magulu omwe ali pachiwopsezo chachikulu komanso chochepa.(HK) IC50 mitengo yamankhwala enieni oletsa khansa m'magulu omwe ali pachiwopsezo chachikulu komanso chochepa.*p <0.05, **p <0.01, ns = osafunikira
Tidawunikanso mgwirizano pakati pa ziwopsezo ndi othandizira omwe amapezeka pagulu la TCGA-PAAD.Tidasaka mankhwala oletsa khansa omwe amagwiritsidwa ntchito kwambiri mu khansa ya pancreatic ndikusanthula kusiyana kwawo kwa IC50 pakati pamagulu omwe ali pachiwopsezo chachikulu komanso chochepa.Zotsatira zinasonyeza kuti mtengo wa IC50 wa AZD.2281 (olaparib) unali wapamwamba mu gulu lachiwopsezo chachikulu, zomwe zimasonyeza kuti odwala PAAD omwe ali m'gulu lachiopsezo akhoza kukhala osagwirizana ndi mankhwala a AZD.2281 (Chithunzi 6H).Kuphatikiza apo, mikhalidwe ya IC50 ya paclitaxel, sorafenib, ndi erlotinib inali yotsika pagulu lachiwopsezo chachikulu (Chithunzi 6I-K).Tidazindikiranso mankhwala 34 oletsa khansa omwe ali ndi IC50 yapamwamba kwambiri pagulu lomwe ali pachiwopsezo chachikulu komanso 34 mankhwala oletsa khansa omwe ali ndi IC50 yotsika pagulu lomwe ali pachiwopsezo chachikulu (Table 2).
Sitingakane kuti ma lncRNA, mRNAs, ndi miRNAs amapezeka kwambiri ndipo amathandizira kwambiri pakukula kwa khansa.Pali umboni wokwanira wotsimikizira gawo lofunikira la mRNA kapena miRNA pakulosera kupulumuka kwathunthu mumitundu ingapo ya khansa.Mosakayikira, zitsanzo zambiri zachiwopsezo zimakhazikitsidwanso pa lncRNAs.Mwachitsanzo, Luo et al.Kafukufuku wasonyeza kuti LINC01094 imagwira ntchito yofunika kwambiri pakukula kwa PC ndi metastasis, ndipo mawu apamwamba a LINC01094 amasonyeza kupulumuka kosauka kwa odwala khansa ya pancreatic [16].Kafukufuku woperekedwa ndi Lin et al.Kafukufuku wasonyeza kuti kutsika kwa lncRNA FLVCR1-AS1 kumalumikizidwa ndi kusazindikira bwino kwa odwala khansa ya pancreatic [17].Komabe, ma lncRNA okhudzana ndi chitetezo chamthupi amakambidwa mochepa potengera kupulumuka kwathunthu kwa odwala khansa.Posachedwapa, ntchito yochuluka yakhala ikuyang'ana pakupanga zitsanzo zachiwopsezo zowonetsera kupulumuka kwa odwala khansa ndikusintha njira zothandizira [18, 19, 20].Pali kuzindikira kokulirapo kwa gawo lofunikira la chitetezo chamthupi polowa mu kuyambitsa khansa, kupita patsogolo, komanso kuyankha kwamankhwala monga chemotherapy.Kafukufuku wambiri watsimikizira kuti maselo a chitetezo chamthupi omwe amalowetsa chotupa amakhala ndi gawo lalikulu poyankha cytotoxic chemotherapy [21, 22, 23].Chotupa chitetezo cha microenvironment ndi chinthu chofunika kwambiri pa kupulumuka kwa odwala chotupa [24, 25].Immunotherapy, makamaka ICI therapy, imagwiritsidwa ntchito kwambiri pochiza zotupa zolimba [26].Ma jini okhudzana ndi chitetezo chamthupi amagwiritsidwa ntchito kwambiri popanga zitsanzo zowopsa.Mwachitsanzo, Su et al.Chiwopsezo chokhudzana ndi chitetezo chamthupi chimachokera ku ma jini opangira mapuloteni kuti athe kulosera za odwala khansa ya ovarian [27].Ma jini osalemba zilembo monga ma lncRNA ndi oyeneranso kupanga zitsanzo zowopsa [28, 29, 30].Luo et al adayesa ma lncRNA anayi okhudzana ndi chitetezo chamthupi ndikupanga chitsanzo cholosera za chiopsezo cha khansa ya khomo lachiberekero [31].Khan et al.Zolemba zonse za 32 zofotokozedwa mosiyanasiyana zidadziwika, ndipo kutengera izi, chitsanzo cholosera chokhala ndi zolembedwa zazikulu za 5 zidakhazikitsidwa, zomwe zidanenedwa ngati chida cholimbikitsidwa kwambiri cholosera kukana kotsimikizika kwa biopsy pambuyo pa kuikidwa kwa impso [32].
Zambiri mwazitsanzozi zimachokera ku milingo ya ma jini, mwina ma jini opangira ma protein kapena ma gene osalemba.Komabe, jini lomwelo limatha kukhala ndi mafotokozedwe osiyanasiyana m'mitundu yosiyanasiyana, mawonekedwe a data komanso mwa odwala osiyanasiyana, zomwe zimapangitsa kuyerekeza kosakhazikika mumitundu yolosera.Mu phunziro ili, tinapanga chitsanzo chololera chokhala ndi ma lncRNA awiri awiri, osadalira mayendedwe enieni.
Mu kafukufukuyu, tidazindikira irlncRNA kwa nthawi yoyamba kudzera pakuwunika kolumikizana ndi majini okhudzana ndi chitetezo chamthupi.Tidawunika 223 DEirlncRNAs mwa kusakanizidwa ndi ma lncRNA owonetsedwa mosiyanasiyana.Chachiwiri, tinapanga matrix a 0-kapena-1 kutengera njira yophatikizira ya DEirlncRNA [31].Kenako tidachita kusanthula kwaunivariate ndi lasso regression kuti tizindikire awiriawiri a DEirlncRNA ndikupanga njira yodziwiratu zoopsa.Tinasanthulanso mgwirizano pakati pa ziwopsezo ndi mawonekedwe azachipatala kwa odwala omwe ali ndi PAAD.Tinapeza kuti chitsanzo chathu cha chiopsezo chodziwikiratu, monga chodziyimira pawokha pa odwala a PAAD, amatha kusiyanitsa bwino odwala apamwamba kuchokera kwa odwala otsika kwambiri ndi odwala otsika kwambiri.Kuphatikiza apo, mitengo ya AUC ya ROC yokhotakhota yachiwopsezo chamtsogolo inali 0,905 pazaneneratu za chaka chimodzi, 0,942 pazaka ziwiri zamtsogolo, ndi 0,966 pakulosera kwazaka zitatu.
Ofufuza adanena kuti odwala omwe ali ndi ma CD8 + T omwe amalowetsa kwambiri amakhala okhudzidwa kwambiri ndi chithandizo cha ICI [33].Kuwonjezeka zili cytotoxic maselo, CD56 NK maselo, NK maselo ndi CD8+ T maselo chotupa chitetezo chamthupi microenvironment kungakhale chimodzi mwa zifukwa chotupa suppressive tingati [34].Kafukufuku wam'mbuyomu adawonetsa kuti kuchuluka kwa chotupa-kulowetsa CD4 (+) T ndi CD8 (+) T kumalumikizidwa kwambiri ndikukhala ndi moyo nthawi yayitali [35].Kulowetsedwa kwa ma cell a CD8 T, kutsika kwa neoantigen, komanso chotupa chochepa kwambiri chomwe chimapangitsa kuti anthu asayankhe ICI therapy [36].Tinapeza kuti chiwerengero cha chiopsezo chinali chosagwirizana ndi ma CD8 + T ndi maselo a NK, kusonyeza kuti odwala omwe ali ndi chiopsezo chachikulu sangakhale oyenerera chithandizo cha ICI ndipo amakhala ndi chidziwitso choyipa.
CD161 ndi chizindikiro cha ma cell akupha zachilengedwe (NK).CD8+CD161+ CAR-transduced T maselo amathandizira mu vivo antitumor efficacy mu HER2+ pancreatic ductal adenocarcinoma xenograft models [37].Immune checkpoint inhibitors imayang'ana cytotoxic T lymphocyte yogwirizana ndi mapuloteni 4 (CTLA-4) ndi mapuloteni opangidwa ndi cell kufa 1 (PD-1)/programmed cell death ligand 1 (PD-L1) njira ndipo ali ndi kuthekera kwakukulu m'malo ambiri.Kufotokozera kwa CTLA-4 ndi CD161 (KLRB1) kumakhala kochepa m'magulu omwe ali ndi chiopsezo chachikulu, kusonyeza kuti odwala omwe ali ndi chiopsezo chachikulu sangakhale oyenerera kulandira chithandizo cha ICI.[38]
Kuti tipeze njira zothandizira odwala omwe ali pachiopsezo chachikulu, tinafufuza mankhwala osiyanasiyana oletsa khansa ndipo tinapeza kuti paclitaxel, sorafenib, ndi erlotinib, zomwe zimagwiritsidwa ntchito kwambiri kwa odwala omwe ali ndi PAAD, zingakhale zoyenera kwa odwala omwe ali ndi PAAD.[33].Zhang et al adapeza kuti kusintha kwa njira iliyonse ya DNA kuwonongeka (DDR) kungayambitse kusazindikira bwino kwa odwala khansa ya prostate [39].Mayesero a Pancreatic Cancer Olaparib Ongoing (POLO) adawonetsa kuti chithandizo chamankhwala chokhazikika ndi olaparib sichikhalabe chotalikirapo poyerekeza ndi placebo pambuyo pa chemotherapy ya mzere woyamba wa platinamu mwa odwala omwe ali ndi pancreatic ductal adenocarcinoma ndi germline BRCA1/2 mutations [40].Izi zimapereka chiyembekezo chachikulu kuti zotsatira za chithandizo zidzasintha kwambiri mu gulu ili la odwala.Mu phunziro ili, mtengo wa IC50 wa AZD.2281 (olaparib) unali wapamwamba mu gulu lachiwopsezo chachikulu, kusonyeza kuti odwala PAAD omwe ali m'gulu lachiopsezo akhoza kukhala osagwirizana ndi mankhwala ndi AZD.2281.
Zolosera zamtsogolo mu kafukufukuyu zimabweretsa zolosera zabwino, koma zimatengera maulosi owunikira.Momwe mungatsimikizire zotsatirazi ndi deta yachipatala ndi funso lofunika.Endoscopic fine needle aspiration ultrasonography (EUS-FNA) yakhala njira yofunikira kwambiri yodziwira zotupa zolimba komanso zapancreatic pancreatic ndi kumva kwa 85% komanso kutsimikizika kwa 98% [41].Kubwera kwa singano za EUS fine-needle biopsy (EUS-FNB) makamaka zimatengera zabwino zomwe zimaganiziridwa pa FNA, monga kulondola kwachidziwitso, kupeza zitsanzo zomwe zimasunga mawonekedwe a histological, ndikupanga minofu yoteteza chitetezo ku matenda ena.madontho apadera [42].Kuwunika mwadongosolo m'mabukuwo kunatsimikizira kuti singano za FNB (makamaka 22G) zimawonetsa bwino kwambiri pakukolola minofu kuchokera ku pancreatic misa [43].Zachipatala, odwala ochepa okha ndi omwe ali oyenerera kuchitidwa opaleshoni yoopsa, ndipo odwala ambiri amakhala ndi zotupa zosagwira ntchito panthawi yoyamba.Muzochita zachipatala, odwala ochepa okha ndi omwe ali oyenera kuchitidwa opaleshoni yoopsa chifukwa odwala ambiri amakhala ndi zotupa zosagwira ntchito panthawi yoyamba.Pambuyo potsimikiziridwa ndi EUS-FNB ndi njira zina, chithandizo chokhazikika chosapanga opaleshoni monga chemotherapy nthawi zambiri chimasankhidwa.Pulogalamu yathu yotsatira yofufuza ndikuyesa chitsanzo chamtsogolo cha kafukufukuyu m'magulu ochita opaleshoni komanso osachita opaleshoni kupyolera mu kuwunika kobwerezabwereza.
Ponseponse, kafukufuku wathu adakhazikitsa njira yatsopano yopangira chiwopsezo chotengera irlncRNA, yomwe idawonetsa kudalirika kwa odwala omwe ali ndi khansa ya kapamba.Chitsanzo chathu chowopsa chingathandize kusiyanitsa odwala omwe ali ndi PAAD omwe ali oyenera kulandira chithandizo chamankhwala.
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Nthawi yotumiza: Sep-22-2023