Kanseri y'igikanka ni imwe mu ndwara zica abantu benshi ku isi kandi nta gipimo cy'uko indwara izabaho. Bityo rero, hakenewe uburyo bwo kumenya neza abarwayi bafite ibyago byinshi byo kurwara kanseri y'igikanka kugira ngo havurwe neza kandi hakorwe neza uburyo aba barwayi bafatwa.
Twabonye amakuru ya RNAseq ya The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq avuye muri database ya UCSC Xena, twasanze lncRNAs zifitanye isano n’ubudahangarwa bw’umubiri (irlncRNAs) binyuze mu isesengura ry’imibanire, kandi twasanze itandukaniro riri hagati ya TCGA n’utunyangingo dusanzwe twa pancreatic adenocarcinoma. DEirlncRNA) twakuye muri TCGA no mu miterere y’utunyangingo twa genotype (GTEx) tw’utunyangingo twa pancreatic. Hakozwe ubundi bushakashatsi bwo gusubira inyuma kwa univariate na lasso kugira ngo hakorwe ingero z’ibimenyetso. Hanyuma twabaruye agace kari munsi y’umurongo w’inyuma maze tumenya agaciro gakwiye ko kumenya abarwayi bafite pancreatic adenocarcinoma ifite ibyago byinshi n’ibike. Kugira ngo tugereranye imiterere y’ubuvuzi, kwinjira mu tunyangingo tw’ubudahangarwa bw’umubiri, ibidukikije bito bigabanya ubudahangarwa bw’umubiri, no kudakira imiti mu barwayi bafite kanseri ya pancreatic ifite ibyago byinshi n’ibike.
Twabonye abantu 20 ba DEirlncRNA kandi dushyira abarwayi mu matsinda hakurikijwe agaciro k’isuzuma. Twagaragaje ko icyitegererezo cyacu cy’isuzuma gifite imikorere igaragara mu guhanura iherezo ry’abarwayi ba PAAD. AUC y’isuzuma rya ROC ni 0.905 ku gipimo cy’umwaka 1, 0.942 ku gipimo cy’imyaka 2, na 0.966 ku gipimo cy’imyaka 3. Abarwayi bafite ibyago byinshi byo kubaho bari bafite igipimo cyo hasi cyo kubaho kandi imiterere mibi y’ubuvuzi. Twagaragaje kandi ko abarwayi bafite ibyago byinshi byo kubaho badakomeye kandi bashobora kugira ubudahangarwa bw’umubiri. Isuzuma ry’imiti irwanya kanseri nka paclitaxel, sorafenib, na erlotinib hashingiwe ku bikoresho byo kubara bishobora kuba bikwiye ku barwayi bafite ibyago byinshi byo kubaho barwaye PAAD.
Muri rusange, ubushakashatsi bwacu bwashyizeho uburyo bushya bwo guhanura indwara bushingiye kuri irlncRNA, bwagaragaje akamaro gakomeye ko guhanura indwara ku barwayi ba kanseri y’indurwe. Uburyo bwacu bwo guhanura indwara bushobora gufasha gutandukanya abarwayi ba PAAD bakwiriye kuvurwa.
Kanseri y'indurwe ni ikibyimba kibi gifite igipimo cyo kubaho cy'imyaka itanu kandi gifite amanota meza. Mu gihe cyo gusuzuma, abarwayi benshi baba bari mu byiciro bikomeye. Mu rwego rw'icyorezo cya COVID-19, abaganga n'abaforomo baba bari mu gitutu gikomeye iyo bavura abarwayi ba kanseri y'indurwe, kandi imiryango y'abarwayi nayo ihura n'ibitutu byinshi iyo ifata ibyemezo byo kuvura [1, 2]. Nubwo hatewe intambwe nini mu kuvura DOAD, nko kuvura indwara ya neoadjuvant, kubaga, kuvura hakoreshejwe imirasire, imiti ya chimiotherapie, kuvura hakoreshejwe uburyo bwa molecular, no gukumira indwara ziterwa n'ubudahangarwa bw'umubiri (ICIs), abarwayi bagera kuri 9% gusa ni bo barokoka imyaka itanu nyuma yo kurwara [3]. ], 4]. Kubera ko ibimenyetso bya mbere bya adenocarcinoma y'indurwe y'indurwe ari ibisanzwe, abarwayi bakunze kuvurwa ko bafite metastases mu cyiciro cya mbere [5]. Kubwibyo, ku murwayi runaka, ubuvuzi bwuzuye bugomba gupima ibyiza n'ibibi by'uburyo bwose bwo kuvura, atari ukugira ngo umuntu akomeze kubaho gusa, ahubwo no kunoza ubuzima bwe [6]. Kubwibyo, icyitegererezo cyiza cyo guhanura ni ngombwa kugira ngo hasuzumwe neza uko umurwayi azagenda [7]. Bityo, ubuvuzi bukwiye bushobora gutoranywa kugira ngo buringanize ubuzima n'imibereho myiza y'abarwayi bafite PAAD.
Igabanuka ribi rya PAAD riterwa ahanini no kudakira imiti ya chimiotherapie. Mu myaka ya vuba aha, imiti igabanya ubudahangarwa bw'umubiri yakoreshejwe cyane mu kuvura ibibyimba bikomeye [8]. Ariko, ikoreshwa rya ICI muri kanseri ya pancreas ntirikunze kugira icyo rigeraho [9]. Kubwibyo, ni ngombwa kumenya abarwayi bashobora kungukirwa n'ubuvuzi bwa ICI.
RNA ndende idakora kode (lncRNA) ni ubwoko bwa RNA idakora kode ifite inyandiko za nucleotides zirenze 200. LncRNA zirakwirakwiriye kandi zigize hafi 80% by'inyandiko z'umuntu [10]. Hari ubushakashatsi bwinshi bwagaragaje ko moderi zishingiye kuri lncRNA zishobora guhanura neza iherezo ry'umurwayi [11, 12]. Urugero, lncRNA 18 zifitanye isano na autophagy zagaragaye ko zitanga ibimenyetso by'ubuhanuzi kuri kanseri y'ibere [13]. Izindi lncRNA esheshatu zifitanye isano n'ubudahangarwa bw'umubiri zakoreshejwe mu kugaragaza imiterere y'ubuhanuzi bwa glioma [14].
Muri kanseri ya pancreas, hari ubushakashatsi bwagaragaje ibimenyetso bishingiye kuri lncRNA kugira ngo hamenyekane niba umurwayi azabaho. Ikimenyetso cya 3-lncRNA cyagaragajwe muri adenocarcinoma ya pancreas gifite agace kari munsi ya ROC curve (AUC) ka 0.742 gusa n'ubuzima rusange (OS) bw'imyaka 3 [15]. Byongeye kandi, agaciro k'igaragazwa rya lncRNA karatandukanye bitewe na genome zitandukanye, imiterere itandukanye y'amakuru, n'abarwayi batandukanye, kandi imikorere y'ikimenyetso cy'ibizamini ntabwo ihamye. Kubwibyo, dukoresha uburyo bushya bwo kwerekana, guhuza no gusubiramo, kugira ngo tubone ibimenyetso bishingiye kuri lncRNA (irlncRNA) bifitanye isano n'ubudahangarwa kugira ngo tubone ikimenyetso cy'ibizamini gihamye kandi gihamye [8].
Amakuru ya RNAseq asanzwe (FPKM) na kanseri y’indurwe ya kanseri ya pancreas. Amakuru ya TCGA na genotype tissue expression (GTEx) yakuwe muri database ya UCSC XENA (https://xenabrowser.net/datapages/). Dosiye za GTF zakuwe muri database ya Ensembl (http://asia.ensembl.org) kandi zikoreshwa mu gukuramo imiterere ya lncRNA muri RNAseq. Twakuyemo gene zijyanye n’ubudahangarwa muri database ya ImmPort (http://www.immport.org) kandi twasanze lncRNA zijyanye n’ubudahangarwa (irlncRNAs) hakoreshejwe isesengura ry’imibanire (p < 0.001, r > 0.4). Kumenya irlncRNAs zigaragaza itandukaniro (DEirlncRNAs) binyuze mu kwambuka irlncRNAs na lncRNAs zigaragaza itandukaniro zakuwe muri database ya GEPIA2 (http://gepia2.cancer-pku.cn/#index) muri cohort ya TCGA-PAAD (|logFC| > 1 na FDR) <0.05).
Ubu buryo bwavuzwe mbere [8]. By’umwihariko, dukora X kugira ngo dusimbuze lncRNA A na lncRNA B. Iyo agaciro k’imvugo ya lncRNA A kari hejuru y’agaciro k’imvugo ya lncRNA B, X isobanurwa nka 1, bitabaye ibyo X isobanurwa nka 0. Kubwibyo, dushobora kubona matrix ya 0 cyangwa - 1. Umurongo ugororotse wa matrix uhagarariye buri rugero, naho umurongo utambitse uhagarariye buri DEirlncRNA ifite agaciro ka 0 cyangwa 1.
Isesengura ry’isubiranyuma ry’impinduka ryakurikiwe na Lasso regression ryakoreshejwe mu gusuzuma pairs za DEirlncRNA zigaragaza icyerekezo. Isesengura ry’isubiranyuma rya lasso ryakoresheje inshuro 10 zisubiramo inshuro 1000 (p < 0.05), hamwe n’ibintu 1000 bidasanzwe kuri buri gipimo. Iyo inshuro za buri pairs za DEirlncRNA zirenze inshuro 100 mu mizingo 1000, pairs za DEirlncRNA zatoranyijwe kugira ngo habeho icyitegererezo cy’ibyago byo guhanura. Hanyuma twakoresheje imbonerahamwe ya AUC kugira ngo tubone agaciro gakwiye ko gushyira abarwayi ba PAAD mu matsinda afite ibyago byinshi n’ibike. Agaciro ka AUC ka buri cyitegererezo na ko kabazwe kandi gashushanywa nk’imbonerahamwe. Iyo imbonerahamwe igeze ku ntera yo hejuru igaragaza agaciro ntarengwa ka AUC, inzira yo kubara irahagarara maze icyitegererezo gifatwa nk’icyitegererezo cyiza. Hakozwe icyitegererezo cya ROC cy’imyaka 1, 3 na 5. Isesengura ry’isubiranyuma ry’impinduka ry’impinduka ryakoreshejwe mu gusuzuma imikorere yigenga y’icyitegererezo cy’ibyago byo guhanura.
Koresha ibikoresho birindwi kugira ngo wige igipimo cy’ubwinjirire bw’uturemangingo tw’umubiri, harimo XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, na CIBERSORT. Amakuru y’ubwinjirire bw’uturemangingo yakuwe muri database ya TIMER2 (http://timer.comp-genomics.org/#tab-5817-3). Itandukaniro riri hagati y’uturemangingo tw’umubiri twinjiye hagati y’amatsinda afite ibyago byinshi n’afite ibyago bike by’icyitegererezo cyubatswe ryasesenguwe hakoreshejwe ikizamini cya Wilcoxon signed-rank, ibisubizo bigaragara muri graph kare. Isesengura rya Spearman ry’isano ryakozwe kugira ngo basesengure isano iri hagati y’agaciro k’ibipimo by’ibyago n’uturemangingo twinjiye mu mubiri tw’umubiri. Igipimo cy’ubwinjirire cyavuyemo cyerekanwa nk’ikimenyetso. Igipimo cy’agaciro cyashyizweho kuri p < 0.05. Ubu buryo bwakozwe hakoreshejwe paki ya R ggplot2. Kugira ngo dusuzume isano iri hagati y’icyitegererezo n’urwego rw’imvugo ya gene bifitanye isano n’igipimo cy’ubwinjirire bw’uturemangingo tw’umubiri, twakoze paki ya ggstatsplot na violin plot violin.
Kugira ngo dusuzume imiterere y’ubuvuzi bwa kanseri y’agakoko gatera kanseri, twabaruye IC50 y’imiti ikoreshwa cyane mu miti ya chimiotherapie muri TCGA-PAAD. Itandukaniro riri hagati y’ibipimo bya kabiri by’imiti igabanya ubukana (IC50) hagati y’amatsinda afite ibyago byinshi n’afite ibyago bike ryagereranyijwe hakoreshejwe ikizamini cya Wilcoxon cyashyizweho umukono, kandi ibisubizo bigaragazwa nk’amasanduku yakozwe hakoreshejwe pRPhetic na ggplot2 muri R. Uburyo bwose bwubahiriza amabwiriza n’amahame bireba.
Imikorere y'ubushakashatsi bwacu igaragara ku Ishusho ya 1. Dukoresheje isesengura ry'isano riri hagati ya lncRNA na genes zijyanye n'ubudahangarwa bw'umubiri, twatoranyije irlncRNA 724 zifite p < 0.01 na r > 0.4. Hanyuma twasesenguye irlncRNA za GEPIA2 zigaragazwa mu buryo butandukanye (Ishusho ya 2A). IrlncRNA 223 zose zagaragajwe mu buryo butandukanye hagati ya adenocarcinoma ya pancreas na tissue isanzwe ya pancreas (|logFC| > 1, FDR < 0.05), zitwa DEirlncRNAs.
Kubaka moderi z'ibyago biteganyijwe. (A) Igishushanyo cy'ibirunga cya lncRNAs zagaragajwe mu buryo butandukanye. (B) Ikwirakwizwa rya lasso coefficients kuri pairs 20 za DEirlncRNA. (C) Itandukaniro ry'ibipimo by'ikwirakwizwa rya LASSO coefficient. (D) Igishushanyo cy'ishyamba kigaragaza isesengura ry'ihindagurika ry'ibipimo by ...
Hanyuma twakoze matrix ya 0 cyangwa 1 duhuza DEirlncRNA 223. Habonetse impande 13.687 za DEirlncRNA. Nyuma yo gusesengura univariate na lasso regression, impande 20 za DEirlncRNA zapimwe kugira ngo hakorwe icyitegererezo cy’ibyago byo guhanura (Ishusho ya 2B-D). Hashingiwe ku byavuye mu isesengura rya Lasso n’isesengura ry’ibyago byinshi, twabaze amanota y’ibyago kuri buri murwayi wo mu itsinda rya TCGA-PAAD (Imbonerahamwe ya 1). Hashingiwe ku byavuye mu isesengura rya lasso regression, twabaze amanota y’ibyago kuri buri murwayi wo mu itsinda rya TCGA-PAAD. AUC y’umurongo wa ROC yari 0.905 ku iteganyagihe ry’umwaka 1 ry’ibyago, 0.942 ku iteganyagihe ry’imyaka 2, na 0.966 ku iteganyagihe ry’imyaka 3 (Ishusho ya 3A-B). Twashyizeho agaciro gakwiye ka 3.105, dushyira abarwayi bo mu itsinda rya TCGA-PAAD mu byiciro by’abafite ibyago byinshi n’abadafite ibyago byinshi, kandi dushushanya ibisubizo by’ubuzima n’amanota y’ibyago kuri buri murwayi (Ishusho ya 3C-E). Isesengura rya Kaplan-Meier ryagaragaje ko ubuzima bw’abarwayi bo mu itsinda rya PAAD mu bafite ibyago byinshi bwari buri hasi cyane ugereranije n’ubw’abarwayi bo mu itsinda ryagize ibyago bike (p < 0.001) (Ishusho ya 3F).
Ireme ry'icyitegererezo cy'ibyago byo guhanura. (A) ROC y'icyitegererezo cy'ibyago byo guhanura. (B) Icyitegererezo cy'ibyago byo guhanura cya ROC cy'imyaka 1, 2, na 3. (C) ROC y'icyitegererezo cy'ibyago byo guhanura. Igaragaza aho igarukira neza. (DE) Ikwirakwizwa ry'uburyo bwo kubaho (D) n'amanota y'ibyago (E). (F) Isesengura rya Kaplan-Meier ku barwayi ba PAAD mu matsinda afite ibyago byinshi n'ibike.
Twakomeje gusuzuma itandukaniro mu manota y’ibyago dukurikije imiterere y’ubuvuzi. Igishushanyo mbonera cy’umurongo (Ishusho ya 4A) kigaragaza isano rusange iri hagati y’imiterere y’ubuvuzi n’amanota y’ibyago. By’umwihariko, abarwayi bakuze bari bafite amanota menshi y’ibyago (Ishusho ya 4B). Byongeye kandi, abarwayi bafite icyiciro cya kabiri bari bafite amanota menshi y’ibyago kurusha abarwayi bafite icyiciro cya mbere (Ishusho ya 4C). Ku bijyanye n’urwego rw’ibibyimba ku barwayi ba PAAD, abarwayi bo mu cyiciro cya 3 bari bafite amanota menshi y’ibyago kurusha abarwayi bo mu cyiciro cya 1 n’icya 2 (Ishusho ya 4D). Twakomeje gukora isesengura rya univariate na multivariate regression kandi twerekanye ko amanota y’ibyago (p < 0.001) n’imyaka (p = 0.045) ari ibintu byigenga ku barwayi bafite PAAD (Ishusho ya 5A-B). Imbonerahamwe ya ROC yagaragaje ko amanota y’ibyago yari arenze andi mashusho y’ubuvuzi mu guhanura ubuzima bw’imyaka 1, 2, na 3 bw’abarwayi bafite PAAD (Ishusho ya 5C-E).
Ibiranga ubuvuzi bw'ingero z'ibyago byo guhanura. Histogram (A) igaragaza (B) imyaka, (C) icyiciro cya kanseri, (D) igipimo cya kanseri, amanota y'ibyago, n'igitsina cy'abarwayi bo mu itsinda rya TCGA-PAAD. **p < 0.01
Isesengura ryigenga ry’ingero z’ibyago byo guhanura. (AB) Isesengura ry’impinduka za Univariate (A) na multivariate (B) ku ingero z’ibyago byo guhanura n’imiterere y’ubuvuzi. (CE) ROC y’imyaka 1, 2, na 3 ku ingero z’ibyago byo guhanura n’imiterere y’ubuvuzi
Kubwibyo, twasuzumye isano iri hagati yigihe n'amanota y'ibyago. Twasanze amanota y'ibyago mu barwayi ba PAAD afitanye isano ritameze neza n'uturemangingo twa CD8+ T na NK (Ishusho ya 6A), bigaragaza ko imikorere y'ubudahangarwa bw'umubiri yagabanutse mu itsinda ry'abantu bafite ibyago byinshi. Twanasuzumye itandukaniro mu kwinjira kw'uturemangingo tw'ubudahangarwa bw'umubiri hagati y'amatsinda afite ibyago byinshi n'ibike kandi dusanga ibisubizo bimwe (Ishusho ya 7). Habayeho kwinjira guke kw'uturemangingo twa CD8+ T na NK mu itsinda ry'abantu bafite ibyago byinshi. Mu myaka ya vuba aha, imiti igabanya ubudahangarwa bw'umubiri (ICIs) yakoreshejwe cyane mu kuvura ibibyimba bikomeye. Ariko, ikoreshwa rya ICI muri kanseri ya pancreas ntiryagize icyo rigeraho gake. Kubwibyo, twasuzumye uburyo imiterere ya genes z'ubudahangarwa bw'umubiri mu matsinda afite ibyago byinshi n'ibike. Twasanze CTLA-4 na CD161 (KLRB1) byagaragaye cyane mu itsinda ry'abantu bafite ibyago bike (Ishusho ya 6B-G), bigaragaza ko abarwayi ba PAAD mu itsinda ry'abantu bafite ibyago bike bashobora kuba bahangayikishijwe na ICI.
Isesengura ry'isano ry'icyitegererezo cy'ibyago byo guhanura no kwinjira mu turemangingo tw'ubudahangarwa. (A) Isano iri hagati y'icyitegererezo cy'ibyago byo guhanura no kwinjira mu turemangingo tw'ubudahangarwa. (BG) Igaragaza imiterere ya gene mu matsinda y'ibyago byinshi n'ibike. (HK) Ingano ya IC50 ku miti yihariye irwanya kanseri mu matsinda y'ibyago byinshi n'ibike. *p < 0.05, **p < 0.01, ns = ntabwo ari ingenzi
Twakomeje gusuzuma isano iri hagati y’amanota y’ibyago n’imiti isanzwe ya chimiotherapie mu itsinda rya TCGA-PAAD. Twashatse imiti isanzwe irwanya kanseri muri kanseri ya pancreas, tunasesengura itandukaniro riri hagati y’agaciro kayo ka IC50 hagati y’amatsinda afite ibyago byinshi n’afite ibyago bike. Ibisubizo byagaragaje ko agaciro ka IC50 ka AZD.2281 (olaparib) kari hejuru mu itsinda rifite ibyago byinshi, bigaragaza ko abarwayi ba PAAD mu itsinda rifite ibyago byinshi bashobora kudakira AZD.2281 (Ishusho ya 6H). Byongeye kandi, agaciro ka IC50 ka paclitaxel, sorafenib, na erlotinib kari hasi mu itsinda rifite ibyago byinshi (Ishusho ya 6I-K). Twakomeje kugaragaza imiti 34 irwanya kanseri ifite agaciro ka IC50 kari hejuru mu itsinda rifite ibyago byinshi n’imiti 34 irwanya kanseri ifite agaciro ka IC50 kari hasi mu itsinda rifite ibyago byinshi (Imbonerahamwe ya 2).
Ntawahakana ko lncRNA, mRNA, na miRNA biriho cyane kandi bigira uruhare runini mu iterambere rya kanseri. Hari ibimenyetso byinshi bishyigikira uruhare runini rwa mRNA cyangwa miRNA mu guhanura ubuzima rusange mu bwoko butandukanye bwa kanseri. Nta gushidikanya ko ingero nyinshi z’ibyago byo guhanura nazo zishingiye kuri lncRNA. Urugero, Luo et al. Ubushakashatsi bwagaragaje ko LINC01094 igira uruhare runini mu kwiyongera no kwangirika kwa PC, kandi ko LINC01094 igaragara cyane bigaragaza ko abarwayi ba kanseri ya pancreas badashoboye kubaho neza [16]. Ubushakashatsi bwatanzwe na Lin et al. Ubushakashatsi bwagaragaje ko kugabanya lncRNA FLVCR1-AS1 bifitanye isano no kudakomeza kubaho neza ku barwayi ba kanseri ya pancreas [17]. Ariko, lncRNA zifitanye isano n’ubudahangarwa bw’umubiri ntizivugwaho cyane mu bijyanye no guhanura ubuzima rusange bw’abarwayi ba kanseri. Vuba aha, hari akazi kenshi kibanze ku kubaka ingero z’ibyago byo guhanura ubuzima bw’abarwayi ba kanseri bityo bigahindura uburyo bwo kuvura [18, 19, 20]. Hari ukwiyongera kw’imenyekana ry’uruhare rw’ubudahangarwa bw’umubiri mu gutangiza kanseri, gutera imbere, no gusubiza ubuvuzi nka chemotherapy. Ubushakashatsi bwinshi bwemeje ko uturemangingo tw’ubudahangarwa twinjira mu turemangingo bigira uruhare runini mu gusubiza chemotherapy itera uburozi [21, 22, 23]. Ibidukikije by’ubudahangarwa bw’umubiri ni ikintu cy’ingenzi mu kurokoka kw’abarwayi ba kanseri [24, 25]. Ubuvuzi bw’imyororokere, cyane cyane ubuvuzi bwa ICI, bukoreshwa cyane mu kuvura ibibyimba bikomeye [26]. Uturemangingo dufitanye isano n’ubudahangarwa bw’umubiri dukoreshwa cyane mu kubaka ingero z’ibyago byo guhanura. Urugero, Su et al. Ingero z’ibyago byo guhanura bishingiye ku ngirabuzimafatizo zishingiye kuri poroteyine zigaragaza imiterere y’abarwayi ba kanseri y’intanga ngore [27]. Uturemangingo tudakoresha inyuguti nka lncRNA na two turakwiriye mu kubaka ingero z’ibyago byo guhanura [28, 29, 30]. Luo et al bapimye lncRNA enye zifitanye isano n’ubudahangarwa bw’umubiri kandi bubatse icyitegererezo cyo guhanura ibyago byo kurwara kanseri y’inkondo y’umura [31]. Khan et al. Inyandiko 32 zagaragajwe mu buryo butandukanye zaragaragaye, kandi hashingiwe kuri ibi, hashyizweho icyitegererezo cy’ubuhanuzi gifite inyandiko 5 z’ingenzi, cyatanzwe nk'igikoresho gisabwa cyane mu guhanura kwangwa kw’impyiko nyuma yo guterwa impyiko [32].
Inyinshi muri izi moderi zishingiye ku rugero rw'igaragazwa ry'uturemangingo, haba mu magene akoresha poroteyine cyangwa mu magene adafite poroteyine. Ariko, gene imwe ishobora kugira agaciro gatandukanye k'igaragazwa mu magene atandukanye, mu buryo bw'amakuru no mu barwayi batandukanye, bigatuma habaho igereranya ridasobanutse mu magene ateganya igihe. Muri ubu bushakashatsi, twubatse moderi ikwiye ifite amapine abiri ya lncRNA, hatitawe ku gaciro nyako k'igaragazwa.
Muri ubu bushakashatsi, twabonye irlncRNA bwa mbere binyuze mu isesengura ry’imibanire y’ibinyabuzima hamwe n’uturemangingo dufitanye isano n’ubudahangarwa bw’umubiri. Twasuzumye DEirlncRNA 223 binyuze mu guhuza imiterere y’uturemangingo hamwe na lncRNA zitandukanye. Icya kabiri, twubatse matrix ya 0-cyangwa 1 dushingiye ku buryo bwa DEirlncRNA bwo guhuza bwasohotse [31]. Hanyuma twakoze isesengura rya univariate na lasso regression kugira ngo tumenye DEirlncRNA pairs zigaragaza imiterere y’ibintu no kubaka icyitegererezo cy’ibyago biteganyijwe. Twakomeje gusesengura isano iri hagati y’amanota y’ibyago n’imiterere y’ubuvuzi ku barwayi ba PAAD. Twasanze icyitegererezo cyacu cy’ibyago biteganijwe, nk’ikintu cyigenga mu guhanura ku barwayi ba PAAD, gishobora gutandukanya neza abarwayi bo mu rwego rwo hejuru n’abarwayi bo mu rwego rwo hasi n’abarwayi bo mu rwego rwo hejuru n’abarwayi bo mu rwego rwo hasi. Byongeye kandi, agaciro ka AUC k’umurongo wa ROC w’icyitegererezo cy’ibyago biteganijwe ni 0.905 ku gipimo cy’umwaka umwe, 0.942 ku gipimo cy’imyaka 2, na 0.966 ku gipimo cy’imyaka 3.
Abashakashatsi bavuze ko abarwayi bafite CD8+ T nyinshi binjira cyane mu mubiri barushagaho kwitabwaho n’imiti ya ICI [33]. Ubwiyongere bw’uturemangingo twa sitojeni, CD56 NK, NK na CD8+ T mu bidukikije bishobora kuba imwe mu mpamvu zituma habaho ingaruka zo kugabanya ikibyimba [34]. Ubushakashatsi bwakozwe mbere bwagaragaje ko urugero rwo hejuru rwa CD4(+) T na CD8(+) T byinjira mu mubiri bifitanye isano rikomeye no kuramba igihe kirekire [35]. Kwinjira nabi kwa CD8 T, umutwaro muto wa neoantigen, hamwe n’ibidukikije bigabanya ubudahangarwa bw’umubiri bituma indwara ya ICI idakira neza [36]. Twasanze amanota y’ibyago yari afitanye isano ribi n’uturemangingo twa CD8+ T na NK, bigaragaza ko abarwayi bafite amanota menshi y’ibyago bashobora kuba badakwiriye kuvurwa na ICI kandi bakaba bafite ibyago byinshi byo kurwara.
CD161 ni ikimenyetso cy'uturemangingo tw’umwicanyi karemano (NK). Uturemangingo twa T twa CD8+CD161+ twahinduwe na CAR dutuma habaho imikorere myiza yo kurwanya kanseri mu mubiri mu buryo bwa HER2+ pancreatic ductal adenocarcinoma xenograft [37]. Ubudahangarwa bw’umubiri bugenzura poroteyine ifitanye isano na lymphocyte T 4 (CTLA-4) na poroteyine ifitanye isano na 1 (PD-1)/PD-L1) kandi bufite ubushobozi bwinshi mu bice byinshi. Kugaragara kwa CTLA-4 na CD161 (KLRB1) biri hasi mu matsinda y’abantu bafite ibyago byinshi, kandi bigaragaza ko abarwayi bafite amanota menshi bashobora kudashobora kuvurwa na ICI. [38]
Kugira ngo tubone uburyo bwo kuvura bukwiriye abarwayi bafite ibyago byinshi, twasesenguye imiti itandukanye irwanya kanseri maze dusanga paclitaxel, sorafenib, na erlotinib, ikoreshwa cyane ku barwayi bafite PAAD, ishobora kuba ikwiriye abarwayi bafite ibyago byinshi barwaye PAAD. [33]. Zhang n'abandi basanze impinduka mu buryo ubwo aribwo bwose bwo kwangirika kwa ADN (DDR) zishobora gutuma abarwayi ba kanseri ya prostate badakomeza kurwara [39]. Igerageza rya Pancreatic Cancer Olaparib Ongoing (POLO) ryagaragaje ko kuvura olaparib mu buryo bwo kuyivura bimara igihe kirekire kandi nta ngaruka mbi ugereranije na placebo nyuma ya chemotherapy ishingiye kuri platinum ku barwayi bafite pancreatic ductal adenocarcinoma na germline BRCA1/2 [40]. Ibi bitanga icyizere gikomeye ko ibisubizo by'ubuvuzi bizatera imbere cyane muri iri tsinda ry'abarwayi. Muri ubu bushakashatsi, agaciro ka IC50 ka AZD.2281 (olaparib) kari hejuru mu itsinda ry'abarwayi bafite ibyago byinshi, bigaragaza ko abarwayi ba PAAD mu itsinda ry'abarwayi bafite ibyago byinshi bashobora kudakira kuvurwa na AZD.2281.
Uburyo bwo guhanura muri ubu bushakashatsi butanga ibisubizo byiza byo guhanura, ariko bushingiye ku bipimo by’isesengura. Uburyo bwo kwemeza ibi bisubizo hakoreshejwe amakuru y’ubuvuzi ni ikibazo cy’ingenzi. Ultrasonography ya Endoscopic fine neckline aspiration (EUS-FNA) yabaye uburyo bw’ingenzi bwo gusuzuma ibisebe bikomeye n’ibitari ibya pancreas bifite ubushobozi bwo kuvura 85% n’ubwihariye bwa 98% [41]. Kuza kw’inshinge za EUS fine-needle biopsy (EUS-FNB) bishingiye ahanini ku byiza bigaragara kurusha FNA, nko kumenya neza indwara, kubona ingero zibungabunga imiterere y’impinduka, bityo bigatuma habaho ubudahangarwa bw’umubiri bukenewe cyane mu gusuzuma bimwe na bimwe. ibara ryihariye [42]. Isuzuma ryakozwe ku buryo bunonosoye ryemeje ko inshinge za FNB (cyane cyane 22G) zigaragaza ubushobozi bwo hejuru mu gukuramo inshinge mu matsinda ya pancreas [43]. Mu buvuzi, umubare muto w’abarwayi ni bo bemerewe kubagwa cyane, kandi abarwayi benshi bafite ibibyimba bidakira mu gihe cyo gusuzuma bwa mbere. Mu buvuzi, igice gito cy’abarwayi ni bo bakwiriye kubagwa cyane kuko abarwayi benshi bafite ibibyimba bidakira mu gihe cyo gusuzuma bwa mbere. Nyuma yo kwemeza indwara hakoreshejwe EUS-FNB n'ubundi buryo, ubusanzwe hatoranywa uburyo busanzwe bwo kuvura indwara zitari izo kubaga nka chimiotherapie. Gahunda yacu y'ubushakashatsi ikurikiraho ni ukugerageza uburyo ubu bushakashatsi bugaragaza niba buzaba bumeze mu matsinda y'abaganga babazwe n'abatabagajwe binyuze mu isesengura ryimbitse.
Muri rusange, ubushakashatsi bwacu bwashyizeho uburyo bushya bwo guhanura indwara bushingiye kuri irlncRNA, bwagaragaje akamaro gakomeye ko guhanura indwara ku barwayi ba kanseri y’indurwe. Uburyo bwacu bwo guhanura indwara bushobora gufasha gutandukanya abarwayi ba PAAD bakwiriye kuvurwa.
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Igihe cyo kohereza: 22 Nzeri 2023