Khansa ya kapamba ndi imodzi mwa zotupa zoopsa kwambiri padziko lonse lapansi zomwe sizikudziwika bwino. Chifukwa chake, njira yolondola yodziwira matenda ikufunika kuti tidziwe odwala omwe ali pachiwopsezo chachikulu cha khansa ya kapamba kuti tisinthe chithandizo ndikuwonjezera mwayi wodziwira matenda kwa odwalawa.
Tinapeza deta ya The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq kuchokera ku database ya UCSC Xena, tinapeza ma lncRNA okhudzana ndi chitetezo chamthupi (irlncRNAs) kudzera mu kusanthula kwa mgwirizano, ndipo tinapeza kusiyana pakati pa TCGA ndi minofu ya pancreatic adenocarcinoma yachibadwa. DEirlncRNA) kuchokera ku TCGA ndi genotype tissue expression (GTEx) ya minofu ya pancreatic. Kusanthula kwina kwa univariate ndi lasso regression kunachitika kuti tipange zitsanzo zosonyeza kuti pali matenda. Kenako tinawerengera dera lomwe lili pansi pa curve ndikupeza mtengo woyenera wopezera odwala omwe ali ndi pancreatic adenocarcinoma yomwe ili pachiwopsezo chachikulu komanso chotsika. Kuti tiyerekezere makhalidwe azachipatala, kulowa kwa maselo a chitetezo chamthupi, chitetezo chamthupi chopondereza, komanso kukana mankhwala a chemotherapy mwa odwala omwe ali ndi khansa ya pancreatic yomwe ili pachiwopsezo chachikulu komanso chotsika.
Tinapeza ma DEirlncRNA awiriawiri ndipo tinagawa odwala m'magulu malinga ndi kuchuluka kwa njira yabwino kwambiri yodziwira matenda. Tinawonetsa kuti chitsanzo chathu chodziwira matenda chili ndi ntchito yayikulu poneneratu za matenda a odwala omwe ali ndi PAAD. AUC ya ROC curve ndi 0.905 pa chaka chimodzi cholosera, 0.942 pa chaka chachiwiri cholosera, ndi 0.966 pa zaka zitatu zolosera. Odwala omwe ali pachiwopsezo chachikulu anali ndi ziwopsezo zochepa zopulumuka komanso zizindikiro zoyipa zachipatala. Tinawonetsanso kuti odwala omwe ali pachiwopsezo chachikulu ali ndi chitetezo chamthupi chofooka ndipo amatha kukhala ndi vuto la chitetezo chamthupi. Kuwunika mankhwala oletsa khansa monga paclitaxel, sorafenib, ndi erlotinib kutengera zida zowerengera za makompyuta kungakhale koyenera kwa odwala omwe ali pachiwopsezo chachikulu omwe ali ndi PAAD.
Ponseponse, kafukufuku wathu adakhazikitsa chitsanzo chatsopano cha chiopsezo cholosera matenda pogwiritsa ntchito irlncRNA yolumikizana, yomwe idawonetsa phindu lalikulu la kulosera matenda mwa odwala omwe ali ndi khansa ya kapamba. Chitsanzo chathu cha chiopsezo cholosera matenda chingathandize kusiyanitsa odwala omwe ali ndi PAAD omwe ali oyenera kulandira chithandizo chamankhwala.
Khansa ya kapamba ndi chotupa choipa chomwe chimakhala ndi moyo wochepa kwa zaka zisanu komanso chiŵerengero chapamwamba. Panthawi yopezeka ndi matendawa, odwala ambiri amakhala kale m'magawo apamwamba. Pankhani ya mliri wa COVID-19, madokotala ndi anamwino amakhala ndi mavuto ambiri akamachiritsa odwala khansa ya kapamba, ndipo mabanja a odwala nawonso amakumana ndi mavuto ambiri popanga zisankho za chithandizo [1, 2]. Ngakhale kuti kupita patsogolo kwakukulu kwachitika pochiza DOADs, monga chithandizo cha neoadjuvant, opaleshoni yochotsa opaleshoni, chithandizo cha radiation, chemotherapy, chithandizo cha molecular, ndi immune checkpoint inhibitors (ICIs), odwala pafupifupi 9% okha ndi omwe amakhala ndi moyo zaka zisanu atapezeka ndi matendawa [3]. ], 4]. Chifukwa zizindikiro zoyambirira za pancreatic adenocarcinoma sizimadziwika, odwala nthawi zambiri amapezeka ndi metastases pamlingo wapamwamba [5]. Chifukwa chake, kwa wodwala wina, chithandizo chokwanira payekhapayekha chiyenera kuyeza zabwino ndi zoyipa za njira zonse zamankhwala, osati kungotalikitsa moyo, komanso kukonza moyo wabwino [6]. Chifukwa chake, chitsanzo chothandiza cholosera ndikofunikira kuti muwone molondola momwe wodwalayo alili [7]. Motero, chithandizo choyenera chingasankhidwe kuti chikhale chogwirizana ndi moyo wa odwala omwe ali ndi PAAD.
Kuchepa kwa zizindikiro za PAAD kumachitika makamaka chifukwa cha kukana mankhwala a chemotherapy. M'zaka zaposachedwapa, mankhwala oletsa chitetezo chamthupi akhala akugwiritsidwa ntchito kwambiri pochiza zotupa zolimba [8]. Komabe, kugwiritsa ntchito mankhwala a ICI mu khansa ya kapamba sikuthandiza kwenikweni [9]. Chifukwa chake, ndikofunikira kuzindikira odwala omwe angapindule ndi chithandizo cha ICI.
RNA yayitali yosalemba ma code (lncRNA) ndi mtundu wa RNA yosalemba ma code yokhala ndi ma nucleotide opitilira 200. Ma LncRNA ndi ofala ndipo amapanga pafupifupi 80% ya transcriptome ya anthu [10]. Ntchito zambiri zasonyeza kuti ma model ofotokoza za lncRNA amatha kulosera bwino za matenda a wodwala [11, 12]. Mwachitsanzo, ma lncRNA 18 okhudzana ndi autophagy adapezeka kuti apanga zizindikiro zolosera za khansa ya m'mawere [13]. Ma lncRNA ena asanu ndi limodzi okhudzana ndi chitetezo chamthupi agwiritsidwa ntchito pokhazikitsa zizindikiro zolosera za glioma [14].
Mu khansa ya kapamba, maphunziro ena apeza zizindikiro zochokera ku lncRNA kuti alosere za matenda a wodwalayo. Chizindikiro cha 3-lncRNA chinapezeka mu pancreatic adenocarcinoma yokhala ndi malo omwe ali pansi pa ROC curve (AUC) ya 0.742 yokha ndi kupulumuka konse (OS) kwa zaka 3 [15]. Kuphatikiza apo, kuchuluka kwa mafotokozedwe a lncRNA kumasiyana pakati pa majini osiyanasiyana, mawonekedwe osiyanasiyana a deta, ndi odwala osiyanasiyana, ndipo magwiridwe antchito a chitsanzo cholosera ndi osakhazikika. Chifukwa chake, timagwiritsa ntchito njira yatsopano yopangira ma modeli, kuphatikiza ndi kubwerezabwereza, kuti tipange zizindikiro zokhudzana ndi chitetezo chamthupi cha lncRNA (irlncRNA) kuti tipange chitsanzo cholosera cholondola komanso chokhazikika [8].
Deta ya RNAseq yokhazikika (FPKM) ndi khansa ya kapamba yodwala TCGA ndi deta ya genotype tissue expression (GTEx) idapezeka kuchokera ku database ya UCSC XENA (https://xenabrowser.net/datapages/). Mafayilo a GTF adapezeka kuchokera ku database ya Ensembl (http://asia.ensembl.org) ndipo adagwiritsidwa ntchito kuchotsa ma profiles a lncRNA expression kuchokera ku RNAseq. Tinatsitsa majini okhudzana ndi chitetezo chamthupi kuchokera ku database ya ImmPort (http://www.immport.org) ndipo tinazindikira ma lncRNA okhudzana ndi chitetezo chamthupi (irlncRNAs) pogwiritsa ntchito kusanthula kwa correlation (p < 0.001, r > 0.4). Kuzindikira ma irlncRNAs ofotokozedwa mosiyana (DEirlncRNAs) podutsa ma irlncRNAs ndi ma lncRNAs ofotokozedwa mosiyana omwe adapezeka kuchokera ku database ya GEPIA2 (http://gepia2.cancer-pku.cn/#index) mu gulu la TCGA-PAAD (|logFC| > 1 ndi FDR) <0.05).
Njira iyi yanenedwa kale [8]. Makamaka, timapanga X kuti tilowe m'malo mwa lncRNA A ndi lncRNA B. Pamene mtengo wa lncRNA A uli wapamwamba kuposa mtengo wa lncRNA B, X imafotokozedwa ngati 1, apo ayi X imafotokozedwa ngati 0. Chifukwa chake, titha kupeza matrix ya 0 kapena - 1. Mzere wowongoka wa matrix umayimira chitsanzo chilichonse, ndipo mzere wopingasa umayimira awiriawiri a DEirlncRNA okhala ndi mtengo wa 0 kapena 1.
Kusanthula kwa univariate regression kutsatiridwa ndi Lasso regression kunagwiritsidwa ntchito pofufuza ma DEirlncRNA awiriawiri ofotokozera za prognostic. Kusanthula kwa lasso regression kunagwiritsa ntchito kutsimikizira kobwerezabwereza ka 10-fold mobwerezabwereza nthawi 1000 (p < 0.05), ndi zinthu 1000 zosasinthika pa kuthamanga kulikonse. Pamene kuchuluka kwa awiriawiri a DEirlncRNA aliwonse kunapitirira nthawi 100 mu ma cycle 1000, ma DEirlncRNA awiriawiri anasankhidwa kuti apange chitsanzo cha chiopsezo cholosera. Kenako tinagwiritsa ntchito AUC curve kuti tipeze mtengo woyenera kwambiri wogawa odwala a PAAD m'magulu omwe ali pachiwopsezo chachikulu komanso chochepa. Mtengo wa AUC wa chitsanzo chilichonse unawerengedwanso ndikujambulidwa ngati curve. Ngati curveyo ikafika pamwamba kwambiri kusonyeza mtengo wapamwamba wa AUC, njira yowerengera imayima ndipo chitsanzocho chimaonedwa kuti ndi choyenera. Ma curve a ROC a zaka 1, 3 ndi 5 adapangidwa. Kusanthula kwa univariate ndi multivariate regression kunagwiritsidwa ntchito pofufuza momwe chitsanzo cha chiopsezo cholosera cha prognostic chikuyendera.
Gwiritsani ntchito zida zisanu ndi ziwiri kuti muphunzire kuchuluka kwa kulowa kwa maselo a chitetezo chamthupi, kuphatikiza XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, ndi CIBERSORT. Deta ya kulowa kwa maselo a chitetezo chamthupi idatsitsidwa kuchokera ku database ya TIMER2 (http://timer.comp-genomics.org/#tab-5817-3). Kusiyana kwa kuchuluka kwa maselo olowa m'thupi pakati pa magulu omwe ali pachiwopsezo chachikulu ndi otsika a chitsanzo chomangidwacho kudasanthulidwa pogwiritsa ntchito mayeso a Wilcoxon signed-rank, zotsatira zake zikuwonetsedwa mu graph ya sikweya. Kusanthula kwa mgwirizano wa Spearman kunachitika kuti kufufuze ubale pakati pa ma values a chiopsezo ndi maselo olowa m'thupi. Coefficient yogwirizana yomwe idapezeka ikuwonetsedwa ngati lollipop. Mulingo wofunikira unakhazikitsidwa pa p < 0.05. Njirayi idachitika pogwiritsa ntchito R package ggplot2. Kuti tiwone ubale pakati pa chitsanzo ndi milingo yowonetsera majini yogwirizana ndi kuchuluka kwa kulowa kwa maselo a chitetezo chamthupi, tidachita ggstatsplot package ndi violin plot visualization.
Kuti tiwone momwe chithandizo cha khansa ya kapamba chimayendera, tinawerengera IC50 ya mankhwala a chemotherapy omwe amagwiritsidwa ntchito kwambiri mu gulu la TCGA-PAAD. Kusiyana kwa kuchuluka kwa theka la zoletsa (IC50) pakati pa magulu omwe ali pachiwopsezo chachikulu ndi chochepa kunayerekezeredwa pogwiritsa ntchito mayeso a Wilcoxon signed-rank, ndipo zotsatira zake zikuwonetsedwa ngati ma boxplot opangidwa pogwiritsa ntchito pRRophetic ndi ggplot2 mu R. Njira zonse zimagwirizana ndi malangizo ndi malamulo oyenera.
Kayendedwe ka ntchito ka kafukufuku wathu kakuwonetsedwa mu Chithunzi 1. Pogwiritsa ntchito kusanthula kwa ubale pakati pa ma lncRNA ndi majini okhudzana ndi chitetezo chamthupi, tinasankha ma irlncRNA 724 okhala ndi p < 0.01 ndi r > 0.4. Kenako tinasanthula ma lncRNA osiyanasiyana a GEPIA2 (Chithunzi 2A). Ma irlncRNA 223 onse adawonetsedwa mosiyana pakati pa pancreatic adenocarcinoma ndi minofu ya pancreatic yachibadwa (|logFC| > 1, FDR < 0.05), yotchedwa DEirlncRNAs.
Kupanga zitsanzo za zoopsa zolosera. (A) Chithunzi cha volcano cha ma lncRNA opangidwa mosiyanasiyana. (B) Kugawa kwa ma coefficient a lasso pa ma pair 20 a DEirlncRNA. (C) Kusiyana pang'ono kwa kuthekera kwa kugawa kwa coefficient ya LASSO. (D) Chithunzi cha nkhalango chomwe chikuwonetsa kusanthula kwa univariate regression kwa ma pair 20 a DEirlncRNA.
Kenako tinapanga matrix 0 kapena 1 pophatikiza ma DEirlncRNA 223. Mapawiri onse 13,687 a DEirlncRNA adapezeka. Pambuyo pa kusanthula kwa univariate ndi lasso regression, mapawiri 20 a DEirlncRNA adayesedwa kuti apange chitsanzo cha chiopsezo cholosera (Chithunzi 2B-D). Kutengera zotsatira za Lasso ndi kusanthula kwa regression yambiri, tinawerengera chiwopsezo cha wodwala aliyense mu gulu la TCGA-PAAD (Table 1). Kutengera zotsatira za kusanthula kwa regression ya lasso, tinawerengera chiwopsezo cha wodwala aliyense mu gulu la TCGA-PAAD. AUC ya ROC curve inali 0.905 pa kulosera kwa chitsanzo cha chiopsezo cha chaka chimodzi, 0.942 pa kulosera kwa zaka ziwiri, ndi 0.966 pa kulosera kwa zaka zitatu (Chithunzi 3A-B). Tinaika chiwerengero chabwino kwambiri cha 3.105, tinagawa odwala a TCGA-PAAD m'magulu omwe ali pachiwopsezo chachikulu ndi chochepa, ndipo tinalemba zotsatira za kupulumuka ndi kugawa kwa zigoli zoopsa kwa wodwala aliyense (Chithunzi 3C-E). Kusanthula kwa Kaplan-Meier kunawonetsa kuti kupulumuka kwa odwala a PAAD m'gulu lomwe lili pachiwopsezo chachikulu kunali kotsika kwambiri kuposa kwa odwala omwe ali pachiwopsezo chochepa (p < 0.001) (Chithunzi 3F).
Kutsimikizika kwa mitundu ya chiopsezo cha kulosera. (A) ROC ya chitsanzo cha chiopsezo cha kulosera. (B) Mitundu ya chiopsezo cha kulosera cha ROC ya zaka 1, 2, ndi 3. (C) ROC ya chitsanzo cha chiopsezo cha kulosera. Ikuwonetsa malo abwino kwambiri omalizira. (DE) Kugawa momwe munthu alili wopulumuka (D) ndi zigoli za chiopsezo (E). (F) Kusanthula kwa Kaplan-Meier kwa odwala a PAAD m'magulu omwe ali pachiwopsezo chachikulu komanso chotsika.
Tinapitiliza kuwunika kusiyana kwa zigoli za chiopsezo potengera makhalidwe achipatala. Chithunzi cha mzere (Chithunzi 4A) chikuwonetsa ubale wonse pakati pa makhalidwe achipatala ndi zigoli za chiopsezo. Makamaka, odwala okalamba anali ndi zigoli za chiopsezo chachikulu (Chithunzi 4B). Kuphatikiza apo, odwala omwe ali ndi gawo lachiwiri anali ndi zigoli za chiopsezo chachikulu kuposa odwala omwe ali ndi gawo I (Chithunzi 4C). Ponena za giredi ya chotupa mwa odwala a PAAD, odwala a giredi 3 anali ndi zigoli za chiopsezo chachikulu kuposa odwala a giredi 1 ndi 2 (Chithunzi 4D). Tinapitiliza kuchita kusanthula kwa univariate ndi multivariate regression ndipo tinawonetsa kuti zigoli za chiopsezo (p < 0.001) ndi zaka (p = 0.045) zinali zinthu zodziyimira pawokha mwa odwala omwe ali ndi PAAD (Chithunzi 5A-B). Mzere wa ROC unawonetsa kuti zigoli za chiopsezo zinali zapamwamba kuposa makhalidwe ena azachipatala poneneratu kupulumuka kwa zaka 1, 2, ndi 3 kwa odwala omwe ali ndi PAAD (Chithunzi 5C-E).
Makhalidwe azachipatala a zitsanzo za chiopsezo cha kulosera. Histogram (A) ikuwonetsa (B) zaka, (C) gawo la chotupa, (D) giredi ya chotupa, kuchuluka kwa chiopsezo, ndi jenda la odwala omwe ali mgulu la TCGA-PAAD. **p < 0.01
Kusanthula kodziyimira pawokha kwa zitsanzo za zoopsa zolosera. (AB) Kusanthula kobwerezabwereza kwa Univariate (A) ndi multivariate (B) kwa zitsanzo za zoopsa zolosera ndi makhalidwe azachipatala. (CE) ROC ya zaka 1-, 2-, ndi 3 ya zitsanzo za zoopsa zolosera ndi makhalidwe azachipatala.
Chifukwa chake, tinayang'ana ubale womwe ulipo pakati pa nthawi ndi zigoli zoopsa. Tinapeza kuti zigoli zoopsa mwa odwala a PAAD zinali zosiyana ndi maselo a CD8+ T ndi maselo a NK (Chithunzi 6A), zomwe zikusonyeza kuti chitetezo chamthupi chachepetsedwa m'gulu la anthu omwe ali pachiwopsezo chachikulu. Tinayang'ananso kusiyana kwa kulowa kwa maselo a chitetezo chamthupi pakati pa magulu omwe ali pachiwopsezo chachikulu ndi omwe ali pachiwopsezo chochepa ndipo tinapeza zotsatira zomwezo (Chithunzi 7). Panali kulowa kochepa kwa maselo a CD8+ T ndi maselo a NK m'gulu la anthu omwe ali pachiwopsezo chachikulu. M'zaka zaposachedwa, zoletsa chitetezo chamthupi (ICIs) zakhala zikugwiritsidwa ntchito kwambiri pochiza zotupa zolimba. Komabe, kugwiritsa ntchito ma ICI mu khansa ya kapamba sikunapambane kawirikawiri. Chifukwa chake, tinayang'ana momwe majini owunikira chitetezo chamthupi amaonekera m'magulu omwe ali pachiwopsezo chachikulu ndi omwe ali pachiwopsezo chochepa. Tinapeza kuti CTLA-4 ndi CD161 (KLRB1) zinali zochulukira m'gulu la anthu omwe ali pachiwopsezo chochepa (Chithunzi 6B-G), zomwe zikusonyeza kuti odwala a PAAD m'gulu la anthu omwe ali pachiwopsezo chochepa akhoza kukhala ndi chidwi ndi ICI.
Kusanthula mgwirizano wa chitsanzo cha chiopsezo cha kulosera ndi kulowa kwa maselo a chitetezo chamthupi. (A) Kugwirizana pakati pa chitsanzo cha chiopsezo cha kulosera ndi kulowa kwa maselo a chitetezo chamthupi. (BG) Kumasonyeza kufotokozera kwa majini m'magulu omwe ali pachiwopsezo chachikulu ndi chochepa. (HK) Ma values a IC50 a mankhwala enaake oletsa khansa m'magulu omwe ali pachiwopsezo chachikulu ndi chochepa. *p < 0.05, **p < 0.01, ns = sikofunikira
Tinayang'ananso mgwirizano pakati pa zigoli zoopsa ndi mankhwala ochiritsira khansa omwe amagwiritsidwa ntchito kwambiri mu gulu la TCGA-PAAD. Tinafufuza mankhwala oletsa khansa omwe amagwiritsidwa ntchito kwambiri mu khansa ya kapamba ndipo tinasanthula kusiyana kwa ma IC50 awo pakati pa magulu omwe ali pachiwopsezo chachikulu ndi omwe ali pachiwopsezo chochepa. Zotsatira zake zinawonetsa kuti mtengo wa IC50 wa AZD.2281 (olaparib) unali wapamwamba kwambiri mu gulu lomwe lili pachiwopsezo chachikulu, zomwe zikusonyeza kuti odwala a PAAD omwe ali pachiwopsezo chachikulu akhoza kukana chithandizo cha AZD.2281 (Chithunzi 6H). Kuphatikiza apo, ma IC50 a paclitaxel, sorafenib, ndi erlotinib anali otsika mu gulu lomwe lili pachiwopsezo chachikulu (Chithunzi 6I-K). Tinapezanso mankhwala 34 oletsa khansa omwe ali ndi ma IC50 apamwamba mu gulu lomwe lili pachiwopsezo chachikulu ndi mankhwala 34 oletsa khansa omwe ali ndi ma IC50 otsika mu gulu lomwe lili pachiwopsezo chachikulu (Table 2).
Sizingakane kuti ma lncRNA, ma mRNA, ndi ma miRNA alipo ambiri ndipo amachita gawo lofunika kwambiri pakukula kwa khansa. Pali umboni wokwanira wotsimikizira udindo wofunikira wa mRNA kapena miRNA poneneratu kupulumuka konse kwa mitundu ingapo ya khansa. Mosakayikira, mitundu yambiri ya zoopsa zolosera imatengeranso ma lncRNA. Mwachitsanzo, Luo et al. Kafukufuku wasonyeza kuti LINC01094 imagwira ntchito yofunika kwambiri pakufalikira kwa PC ndi kufalikira kwa maselo, ndipo kuchuluka kwa LINC01094 kumasonyeza kupulumuka kochepa kwa odwala khansa ya kapamba [16]. Kafukufuku woperekedwa ndi Lin et al. Kafukufuku wasonyeza kuti kuchepetsa lncRNA FLVCR1-AS1 kumagwirizanitsidwa ndi kutsika kwa chiyembekezo mwa odwala khansa ya kapamba [17]. Komabe, ma lncRNA okhudzana ndi chitetezo chamthupi sakukambidwa kwambiri pankhani yoneneratu kupulumuka konse kwa odwala khansa. Posachedwapa, ntchito yambiri yakhala ikuyang'ana kwambiri pakupanga mitundu ya zoopsa zolosera kuti alosere kupulumuka kwa odwala khansa ndikusinthira njira zamankhwala [18, 19, 20]. Pali kuzindikira kwakukulu kwa kufunika kwa chitetezo chamthupi chomwe chimalowa m'thupi poyambitsa khansa, kupita patsogolo, komanso kuyankha mankhwala monga chemotherapy. Kafukufuku wambiri watsimikizira kuti maselo a chitetezo chamthupi omwe amalowa m'thupi amachita gawo lofunika kwambiri pakuyankha mankhwala a cytotoxic [21, 22, 23]. Malo oteteza chitetezo chamthupi m'thupi ndi chinthu chofunikira kwambiri pakupulumuka kwa odwala khansa [24, 25]. Chithandizo cha immunotherapy, makamaka chithandizo cha ICI, chimagwiritsidwa ntchito kwambiri pochiza zotupa zolimba [26]. Majini okhudzana ndi chitetezo chamthupi amagwiritsidwa ntchito kwambiri popanga mitundu yowopsa ya matenda. Mwachitsanzo, Su et al. Chitsanzo cha chiopsezo cha matenda okhudzana ndi chitetezo chamthupi chimachokera ku majini olembera mapuloteni kuti alosere za matenda a khansa ya m'chiberekero [27]. Majini osalembera monga lncRNA nawonso ndi oyenera kupanga mitundu yowopsa ya matenda [28, 29, 30]. Luo et al adayesa ma lncRNA anayi okhudzana ndi chitetezo chamthupi ndipo adapanga chitsanzo cholosera za chiopsezo cha khansa ya pachibelekero [31]. Khan et al. Zolembedwa 32 zosiyanasiyana zinapezeka, ndipo potengera izi, chitsanzo cholosera chokhala ndi zolemba 5 zofunika kwambiri chinakhazikitsidwa, chomwe chinaperekedwa ngati chida cholimbikitsidwa kwambiri cholosera kukana kwadzidzidzi kwa biopsy pambuyo poika impso [32].
Ambiri mwa mitundu iyi amachokera pa kuchuluka kwa majini, kaya majini olembera mapuloteni kapena majini osalembera. Komabe, majini omwewo amatha kukhala ndi mitundu yosiyanasiyana ya mafotokozedwe m'ma genome osiyanasiyana, mawonekedwe a deta komanso mwa odwala osiyanasiyana, zomwe zimapangitsa kuti pakhale kuyerekezera kosakhazikika m'ma model oneneratu. Mu kafukufukuyu, tinapanga chitsanzo choyenera chokhala ndi ma lncRNA awiriawiri, osadalira mitundu yeniyeni ya mafotokozedwe.
Mu kafukufukuyu, tinazindikira irlncRNA koyamba kudzera mu kusanthula kwa ubale ndi majini okhudzana ndi chitetezo chamthupi. Tinayesa ma DEirlncRNA 223 mwa kusakaniza ndi ma lncRNA ofotokozedwa mosiyana. Chachiwiri, tinapanga matrix a 0-kapena-1 kutengera njira yofalitsa ya DEirlncRNA [31]. Kenako tinachita kusanthula kwa univariate ndi lasso regression kuti tizindikire ma DEirlncRNA awiriawiri ofotokozera ndikupanga chitsanzo cha chiopsezo cholosera. Tinafufuzanso mgwirizano pakati pa zigoli zoopsa ndi makhalidwe azachipatala mwa odwala omwe ali ndi PAAD. Tinapeza kuti chitsanzo chathu cha chiopsezo cholosera, monga chinthu chodziyimira pawokha cholosera mwa odwala a PAAD, chingathe kusiyanitsa bwino odwala apamwamba ndi odwala otsika komanso odwala apamwamba ndi odwala otsika. Kuphatikiza apo, ma AUC values a ROC curve a chitsanzo cha chiopsezo cholosera anali 0.905 pa kulosera kwa chaka chimodzi, 0.942 pa kulosera kwa zaka ziwiri, ndi 0.966 pa kulosera kwa zaka zitatu.
Ofufuza adanena kuti odwala omwe ali ndi kuchuluka kwa maselo a CD8+ T anali okhudzidwa kwambiri ndi chithandizo cha ICI [33]. Kuwonjezeka kwa kuchuluka kwa maselo a cytotoxic, maselo a CD56 NK, maselo a NK ndi maselo a CD8+ T m'malo oteteza chitetezo chamthupi kungakhale chimodzi mwa zifukwa zomwe zimayambitsa zotsatira zoletsa chotupa [34]. Kafukufuku wakale adawonetsa kuti kuchuluka kwa maselo a CD4(+) T ndi CD8(+) T olowa m'thupi kunalumikizidwa kwambiri ndi kupulumuka kwa nthawi yayitali [35]. Kulowa kwa maselo a CD8 T moyipa, kuchepa kwa neoantigen, komanso malo oteteza chitetezo chamthupi kwambiri kumapangitsa kuti anthu asayankhe chithandizo cha ICI [36]. Tapeza kuti chiwerengero cha chiopsezo chinali chosagwirizana ndi maselo a CD8+ T ndi maselo a NK, zomwe zikusonyeza kuti odwala omwe ali ndi chiwerengero chachikulu cha chiopsezo sangakhale oyenera chithandizo cha ICI ndipo ali ndi chiopsezo choyipa.
CD161 ndi chizindikiro cha maselo akupha mwachilengedwe (NK). Maselo a T opangidwa ndi CD8+CD161+ CAR amalimbikitsa mphamvu yolimbana ndi chotupa mu HER2+ pancreatic ductal adenocarcinoma xenograft models [37]. Zoletsa chitetezo chamthupi zimalimbana ndi cytotoxic T lymphocyte associated protein 4 (CTLA-4) ndi programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways ndipo zimakhala ndi kuthekera kwakukulu m'malo ambiri. Kuchuluka kwa CTLA-4 ndi CD161 (KLRB1) kumakhala kochepa m'magulu omwe ali pachiwopsezo chachikulu, zomwe zikusonyezanso kuti odwala omwe ali pachiwopsezo chachikulu sangakhale oyenerera kulandira chithandizo cha ICI. [38]
Kuti tipeze njira zochiritsira zoyenera odwala omwe ali pachiwopsezo chachikulu, tidasanthula mankhwala osiyanasiyana oletsa khansa ndipo tidapeza kuti paclitaxel, sorafenib, ndi erlotinib, zomwe zimagwiritsidwa ntchito kwambiri mwa odwala omwe ali ndi PAAD, zitha kukhala zoyenera kwa odwala omwe ali pachiwopsezo chachikulu omwe ali ndi PAAD. [33]. Zhang et al adapeza kuti kusintha kwa DNA (DDR) panjira iliyonse kungayambitse matenda osachiritsika mwa odwala khansa ya prostate [39]. Kafukufuku wa Pancreatic Cancer Olaparib Ongoing (POLO) adawonetsa kuti chithandizo chosamalira ndi olaparib chimapitirizabe kukhala ndi moyo wopanda kupita patsogolo poyerekeza ndi placebo pambuyo pa chemotherapy yoyamba ya platinum mwa odwala omwe ali ndi pancreatic ductal adenocarcinoma ndi germline BRCA1/2 mutations [40]. Izi zimapereka chiyembekezo chachikulu kuti zotsatira za chithandizo zidzasintha kwambiri m'gulu laling'ono la odwala. Mu kafukufukuyu, mtengo wa IC50 wa AZD.2281 (olaparib) unali wapamwamba m'gulu lomwe lili pachiwopsezo chachikulu, zomwe zikusonyeza kuti odwala a PAAD omwe ali pachiwopsezo chachikulu akhoza kukana chithandizo ndi AZD.2281.
Zitsanzo zolosera mu kafukufukuyu zikupereka zotsatira zabwino zolosera, koma zimachokera ku zolosera zowunikira. Momwe mungatsimikizire zotsatirazi ndi deta yachipatala ndi funso lofunika kwambiri. Endoscopic fine needle aspiration ultrasonography (EUS-FNA) yakhala njira yofunika kwambiri yodziwira zilonda zolimba komanso zakunja kwa pancreatic zomwe zimakhala ndi mphamvu ya 85% komanso 98% yeniyeni [41]. Kubwera kwa singano za EUS fine-needle biopsy (EUS-FNB) makamaka kumadalira zabwino zomwe zimawonedwa kuposa FNA, monga kulondola kwambiri kwa matenda, kupeza zitsanzo zomwe zimasunga kapangidwe ka histological, ndikupanga minofu yoteteza chitetezo yomwe ndi yofunika kwambiri pa matenda ena. utoto wapadera [42]. Kuwunikanso mwadongosolo kwa mabukuwa kunatsimikizira kuti singano za FNB (makamaka 22G) zikuwonetsa bwino kwambiri pakusonkhanitsa minofu kuchokera ku pancreatic masses [43]. Mwachipatala, odwala ochepa okha ndi omwe ali oyenerera opaleshoni ya radical, ndipo odwala ambiri ali ndi zotupa zosatha kuchitidwa opaleshoni panthawi yodziwira koyamba. Muzochitika zachipatala, odwala ochepa okha ndi omwe ali oyenera opaleshoni ya radical chifukwa odwala ambiri ali ndi zotupa zosatha kuchitidwa opaleshoni panthawi yodziwira koyamba. Pambuyo potsimikizira matenda ndi EUS-FNB ndi njira zina, chithandizo chokhazikika chopanda opaleshoni monga chemotherapy nthawi zambiri chimasankhidwa. Pulogalamu yathu yotsatira yofufuza ndi kuyesa chitsanzo cha kulosera za kafukufukuyu m'magulu opaleshoni ndi osapaleshoni kudzera mu kusanthula kobwerera m'mbuyo.
Ponseponse, kafukufuku wathu adakhazikitsa chitsanzo chatsopano cha chiopsezo cholosera matenda pogwiritsa ntchito irlncRNA yolumikizana, yomwe idawonetsa phindu lalikulu la kulosera matenda mwa odwala omwe ali ndi khansa ya kapamba. Chitsanzo chathu cha chiopsezo cholosera matenda chingathandize kusiyanitsa odwala omwe ali ndi PAAD omwe ali oyenera kulandira chithandizo chamankhwala.
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Nthawi yotumizira: Sep-22-2023