Kev Ntsuam Xyuas Ntawm VEGFA hauv Lub Raum Cell Carcinoma: Kev Qhia, Kev Pom Zoo, Kev Cai Txheej Txheem Txheej Txheem thiab Cov Hom Phiaj

edmund.chen@wecistanche.com

Taw qhia

Lub raum cell carcinoma (RCC), feem ntau malignant qog nyob rau hauvraum, yog ib qho ntawm 10 feem ntau mob qog noj ntshav thoob ntiaj teb.1 Nws suav txog kwv yees li 330,000 mob qog noj ntshav thoob ntiaj teb, thiab ntau dua 140,000 cov neeg tuag txhua xyoo.2 Ntawm cov kab mob sib txawv ntawm RCC,raum lub raumpapillary cell carcinoma (KIRP) nyob rau qib thib ob ntawm cov xwm txheej, suav txog 10 feem pua ​​-15 feem pua ​​​​ntawm RCCs, tom qab ntawdlub raumclear cell carcinoma (KIRC) nrog rau qhov tshwm sim ntawm 75 feem pua ​​– 80 feem pua ​​.3Lub raumchromophobe (KICH) yog ib qho tsis tshua muaj subtype ntawm RCC, suav txog kwv yees li 4 feem pua ​​-5 feem pua ​​​​ntawm RCCs.4 Advanced RCC yog ib tus kab mob tuag taus, nrog rau 5-xyoo ciaj sia taus tsuas yog 11.7 feem pua ​​.5 Kev phais thiab kev kho mob. yog cov txheej txheem kho mob tseem ceeb rau RCC.6 Cov kev sim tshuaj uas cuam tshuam tau pom tias kev siv cov tshuaj tiv thaiv kab mob tiv thaiv kab mob ua ke nrog cov tshuaj antiangiogenic muaj txiaj ntsig zoo dua rau cov neeg mob RCC.7,8 Txawm li cas los xij, cov txheej txheem immunotherapy-raws li tshiab kuj ntsib ntau yam teeb meem. hauv kev siv tshuaj kho mob. Nws yog qhov yuav tsum tau ceev nrooj txhawm rau txheeb xyuas cov hom phiaj kho mob zoo dua thiab txoj hauv kev rau kev kho RCC.

Vascular endothelial growth factor A (VEGFA), qhov tseem ceeb angiogenic yam, yog ib qho tseem ceeb ntawm cov qog nqaij hlav hauv cov neeg mob RCC thiab ua lub luag haujlwm tseem ceeb hauv cov qog angiogenesis thiab kev loj hlob.9 VEGFA induces adhesion thiab migration ntawm cov qog nqaij hlav cancer los ntawm kev khi rau integrin. 9 1.10 Ob peb VEGFA inhibitors muaj txiaj ntsig zoo.11,12 Sunitinib, avascular tyrosine kinase inhibitor ntawm VEGF, tau pom zoo rau thawj- thiab thib ob-kab kev kho mob ntawm RCC siab heev. Txawm li cas los xij, sunitinib tuaj yeem ua rauraum puasthiab mob plawv tsis ua hauj lwm.11 Txawm hais tias VEGFA raug suav hais tias yog ib qho tseem ceeb ntawm cov qog nqaij hlav hauv cov neeg mob RCC, qhov qhia theem, kev tswj cov noob caj noob ces, tus nqi prognostic, thiab kev tswj lub hom phiaj ntawm VEGFA hauv cov neeg mob uas muaj ntau hom kab mob ntawm RCC (KIRC, KICH, thiab KIRP) tseem tsis tau paub txog. Yog li ntawd, nws yog ib qho tsim nyog kom tau txais cov ntaub ntawv tseem ceeb ntawm kev sib raug zoo ntawm VEGFA qhia thiab RCC tshwm sim. Hauv kev tshawb fawb tam sim no, peb tau siv ntau cov ntaub ntawv pub dawb hauv online los txheeb xyuas cov theem qhia, kev tswj cov noob caj noob ces, tus nqi prognostic, thiab kev tswj lub hom phiaj ntawm VEGFA hauv cov neeg mob RCC. Tsis tas li ntawd, txoj kev tshawb no tsom mus ntxiv kev tshawb fawb txog kev sib raug zoo ntawm VEGFA qhia thiab RCC tshwm sim thiab muab kev nkag siab tshiab rau hauv lub hom phiaj kho cov neeg mob nrog RCC.

Ntsiab lus:Lub raum cell carcinoma, lub raum lub raum clear cell carcinoma, raum chromophobe, raum raum papillary cell carcinoma, VEGFA, gene regulation network, phiaj los nqis tes

CISTANCHE yuav txhim kho rau lub raum/ raum mob

Cov ntaub ntawv thiab cov txheej txheem

UAS AnalysisUALCAN (http://ualcan.path.uab.edu/analysis.html) is a online database use as a tool for tumor subgroup gene expression and survival analyses.13,Lub "Kev Ntsuas Kev Ntsuas" module ntawm ALCAN database tau siv los txheeb xyuas TCGA gene qhia cov ntaub ntawv, thiab cov txheej txheem tshuaj ntsuam tau teeb tsa raws li hauv qab no: (a) noob: VEGFA; (b) dataset: KIRC, KICH, thiab KIRP; (c) qhov chaw pib teeb tsa: P-tus nqi txiav tawm =0.05. Cov tub ntxhais kawm qhov t-test tau siv rau kev sib piv.Gene expression profile tsom xamGene expression Profileing Analysis (GEPIA)http://gepia.mob qog noj ntshav-pku.cn/index.html) yog lub vev xaib pub dawb online uas muab cov ntaub ntawv qhia RNA sib luag ntawm 9736 qog thiab 8587 cov qauv ib txwm rau kev tshuaj xyuas 14 qhov sib txawv ntawm mRNA kev qhia, txhawb nqa methylation, theem kab mob, thiab kev sib raug zoo hauv txoj kev tshawb no. Cov kev tshuaj ntsuam xyuas tau raws li hauv qab no: (a) noob: VEGFA; (b) dataset: KIRC, KICH, thiab KIRP; (c) qhov chaw pib teeb tsa: P-tus nqi txiav tawm =0.05. Tus tub ntxhais kawm qhov t-test tau siv los txheeb xyuas qhov kev qhia ntawm VEGFA thiab theem pathological ntawm RCC. Lub Kaplan-Meier nkhaus tau siv los txheeb xyuas qhov tshwm sim ntawm cov neeg mob RCC.cBioPortal tsom xamLub cBioPortal (http://cbioportal.org) yog qhov qhib online database siv los pom, kawm, thiab txheeb xyuas cov ntaub ntawv kab mob qog noj ntshav.15 Hauv peb txoj kev tshawb fawb, kev soj ntsuam ntawm kev hloov pauv caj ces ntawm VEGFA thiab nws cov noob nyob sib ze (saum 5{{ 9}} hloov cov noob nyob sib ze ntawm VEGFA) tau ua los ntawm cBioPortal database. Cov kev tshuaj ntsuam xyuas tau raws li hauv qab no: (a) 446, 66, thiab 274 cov qauv ntawm KIRC, KICH, thiab KIRP, raws li, tau txheeb xyuas; (b) mRNA qhia z-cov qhab nia txheeb ze rau tag nrho cov qauv (log RNA Seq V2 RSEM) tau txais siv z-score pib ntawm ± 2.0; (c) gene: VEGFA.STRING tsom xamSTRING (https://string-db.org/cgi/input.pl) yog online dawb database siv los tsim cov protein-protein interaction (PPI) tes hauj lwm ntawm cov hom phiaj proteins.16 Hauv txoj kev tshawb no, peb tsim PPI network kev sib cuam tshuam los ntawm kev tshuaj ntsuam xyuas nrog kev ntseeg siab tsawg (0.150) thiab txhais hom homo sapiens.GeneMANIA tsom xamGeneMANIA (http://www.genemania.org) yog ib qho cuab yeej tsom xam rau kev tsim PPIs, tsim cov kev xav txog cov noob muaj nuj nqi, txheeb xyuas cov npe ntawm cov noob, thiab sib txuas cov noob rau kev txiav txim siab ua haujlwm.17 Hauv txoj kev tshawb no, peb tsim kev sib koom tes sib txuas rau kev tshawb nrhiav lub luag haujlwm. ntawm VEGFA thiab sab saum toj 50 hloov cov noob nyob sib ze.Metascape tsom xamMetascape (https://metascape.org) yog ib qho yooj yim thiab muaj zog gene function annotation thiab tsom xam cov cuab yeej uas tuaj yeem pab cov neeg siv siv cov kev tshawb fawb bioinformatics nrov tam sim no rau kev tshuaj xyuas cov noob caj noob ces thiab cov protein kom nkag siab txog cov noob caj noob ces lossis cov protein ua haujlwm.18 Hauv peb txoj kev tshawb fawb, Gene Ontology (GO) muaj nuj nqi thiab Kyoto Encyclopedia ntawm Genes thiab Genomes (KEGG) txoj kev txhim kho kev txheeb xyuas ntawm VEGFA thiab nws cov noob nyob sib ze hauv RCC tau tshawb xyuas siv Metascape.TRUST tsom xamTRUST (https://www.grnpedia.orgtrrust/) yog ib daim ntawv teev cov ntaub ntawv khaws tseg ntawm tib neeg kev tswj hwm kev sib txuas lus uas muaj 8444 thiab 6552 kev sib txuas lus-factor-target kev sib raug zoo ntawm 800 human transcription factors.19 Hauv txoj kev tshawb no, peb tau sim ua txheeb xyuas qhov tseem ceeb ntawm kev tswj hwm qhov kev qhia ntawm VEGFA thiab nws cov kev hloov pauv cov noob nyob sib ze hauv cov neeg mob RCC siv TRUST database.LinkedOmic tsom xamLinkedOmics (http://www.linkedomics.org) yog pej xeem online platform uas suav nrog ntau cov ntaub ntawv omics los ntawm tag nrho 32 TCGA hom mob qog noj ntshav.20 Nws muab txoj hauv kev los tshuaj xyuas thiab sib piv cov ntaub ntawv mob qog noj ntshav ntau hauv thiab thoob plaws hom qog. Hauv peb txoj kev tshawb fawb, kinase lub hom phiaj enrichment, miRNA lub hom phiaj enrichment, thiab cov noob sib txawv qhia nyob rau hauv kev sib raug zoo nrog VEGFA tau siv lub "LinkInterpreter" module ntawm LinkedOmics. Cov txheej txheem kev tshuaj ntsuam tau teeb tsa raws li hauv qab no: (a) tsawg kawg ntawm peb lub noob (loj); (b) Hom mob qog noj ntshav: KIRC, KICH, thiab KIRP; (c) simulation ntawm 500; (d) kev tshawb nrhiav: VEGFA thiab saum 50 hloov cov noob nyob sib ze; (e) phiaj xwm dataset: RNA-seq (data type).Timer tsom xamTIMER (https://cistrome.shinyapps.io/timer/) yog ib qho kev pab cuam rau kev soj ntsuam ntawm cov qog-infiltrating lub cev tiv thaiv kab mob, suav nrog B hlwb, CD4 ntxiv rau T hlwb, CD8 ntxiv rau T hlwb, neutrophils, macrophages, thiab dendritic. cells.21 Hauv peb txoj kev tshawb fawb, kev sib raug zoo ntawm VEGFA qhia theem thiab kev nkag mus ntawm lub cev tiv thaiv kab mob tau soj ntsuam los ntawm "gene module" ntawm TIMER.

Cov txiaj ntsig

VEGFA qhia hauv cov neeg mob RCCPeb muab piv rau cov theem qhia ntawm VEGFA hauv cov neeg mob RCC uas muaj tib neeg cov ntaub so ntswg, thiab pom tias cov qib transcriptional ntawm VEGFA stratified los ntawm cov qauv hom, poj niam txiv neej, thiab KIRC pathological theem tau nce siab (P < {{0}}}="" .001)="" (daim="" duab="" 1(a)="" txog="" (c)).="" ib="" yam="" li="" ntawd,="" theem="" qhia="" ntawm="" vegfa="" hauv="" kich="" cov="" ntaub="" so="" ntswg="" tau="" nce="" raws="" li="" cov="" qauv="" qauv,="" poj="" niam="" txiv="" neej,="" thiab="" kich="" theem="" 2="" (p=""><0.05) (daim="" duab="" 1(d)="" rau="" (f)).="" txawm="" li="" cas="" los="" xij,="" theem="" kev="" qhia="" ntawm="" vegfa="" hauv="" kirp="" cov="" ntaub="" so="" ntswg="" raug="" txo="" qis="" raws="" li="" hom="" qauv="" thiab="" poj="" niam="" txiv="" neej="" (p=""><0.05) (daim="" duab="" 1(g)="" thiab="" (h)).="" tsis="" tas="" li="" ntawd,="" peb="" tau="" soj="" ntsuam="" qhov="" sib="" txheeb="" ntawm="" qhov="" sib="" txawv="" ntawm="" vegfa="" thiab="" cov="" theem="" pathological="" hauv="" cov="" neeg="" mob="" rcc.="" peb="" cov="" txiaj="" ntsig="" tau="" pom="" muaj="" kev="" sib="" raug="" zoo="" ntawm="" qhov="" kev="" qhia="" ntawm="" vegfa="" thiab="" theem="" pathological="" hauv="" cov="" neeg="" mob="" kirc="" (p="0.0471)" thiab="" kirp="" (p="4.36e-6)" (daim="" duab="" 2)="" .="" tsis="" tas="" li="" ntawd,="" peb="" siv="" gepia="" los="" ntsuas="" qhov="" kev="" ntsuas="" tus="" nqi="" ntawm="" vegfa="" qhia="" hauv="" cov="" neeg="" mob="" rcc.="" tag="" nrho="" cov="" ciaj="" sia="" nyob="" ntev="" dua="" nyob="" rau="" hauv="" cov="" neeg="" mob="" uas="" muaj="" kirp="" muaj="" tsawg="" dua="" li="" cov="" qib="" vegfa="" siab="" (p="0.00044)" (daim="" duab="" 3(c)).="" qhov="" feem="" pua="" ​​​​muaj="" sia="" nyob="" tau="" siab="" dua="" hauv="" cov="" neeg="" mob="" kirp="" uas="" muaj="" qis="" dua="" siab="" vegfa="" qhia="" qib="" ua="" ntej="" 100="" lub="" hlis="" (p="0.0016)" (daim="" duab="" 3(f)).="" txawm="" li="" cas="" los="" xij,="" qhov="" tshwm="" sim="" tsis="" sib="" xws="" tau="" pom="" tom="" qab="" 100="" lub="" hlis="" hauv="" cov="" neeg="" mob="" kirp="" (daim="" duab="">

Kev hloov pauv caj ces thiab txhawb nqa methylation qib ntawm VEGFA qhia hauv cov neeg mob RCCKev hloov pauv caj ces ntawm VEGFA hauv cov neeg mob nrog RCC tau soj ntsuam siv TCGA. Peb cov txiaj ntsig tau pom tias VEGFA qhia tau hloov pauv los ntawm 4 feem pua ​​​​hauv cov neeg mob KIRC (Cov Duab Ntxiv 1(a)). Txawm li cas los xij, qib kev txhawb nqa methylation ntawm VEGFA qhia tau qis dua hauv cov neeg mob KIRC dua li tib neeg ib txwm muaj (Cov duab ntxiv 1(b)). Ntxiv mus, peb pom 8 feem pua ​​​​VEGFA qhia theem hloov pauv hauv cov neeg mob KICH (Cov duab ntxiv 1(c)). Ib yam li ntawd, VEGFA qhia tau hloov pauv los ntawm 4 feem pua ​​​​hauv cov neeg mob KIRP (Ntxiv daim duab 1(e)). Txawm li cas los xij, qib kev txhawb nqa methylation ntawm VEGFA qhia tau siab dua hauv cov neeg mob uas muaj kab mob theem 1 KIRP dua li cov tib neeg ib txwm muaj (Cov duab ntxiv 1(f))

Kev hloov pauv noob nyob sib ze thiab VEGFA kev sib cuam tshuam network hauv cov neeg mob RCCKev hloov pauv noob nyob sib ze ntawm VEGFA qhia hauv cov neeg mob RCC tau txheeb xyuas siv cBioPortal software. Peb pom VEGFA cov noob nyob sib ze hloov pauv ntau zaus Ntau dua lossis sib npaug li 11.11 feem pua, Ntau dua lossis sib npaug li 20 feem pua, thiab Ntau dua lossis sib npaug li 9.09 feem pua ​​(50 feem ntau hloov cov noob nyob sib ze) hauv cov neeg mob KIRC, KICH, thiab KIRP, raws li (Cov Lus Qhia Ntxiv 1–3). Feem ntau hloov VEGFA cov noob nyob sib ze hauv cov neeg mob KIRC yog VHL (72.22 feem pua), PBRM1 (33.33%), thiab MUC16 (22.22 feem pua) (Table 1). Tsis tas li ntawd, TRRAP (60.00%), PABPC1 (60. KICH (Ntxiv ntxiv) Table 2). Peb feem ntau hloov pauv VEGFA cov noob nyob sib ze hauv cov neeg mob KIRP yog BAP1 (27.27 feem pua), MS4A15 (18.18%), thiab TGM7 (18.18 feem pua) (Table 3).

Tom qab ntawd peb tshawb nrhiav qhov muaj peev xwm cuam tshuam ntawm VEGFA thiab nws cov noob nyob sib ze. PPI network tau tsim los siv STRING software. Peb tau txais 43 nodes thiab 95 npoo hauv PPI tes hauj lwm hauv cov neeg mob KIRC (Cov duab ntxiv 2(a)). Ntxiv mus, peptidyl lysine trimethylation, peptidyl-lysine methylation, extracellular matrix, thiab protein O-linked glycosylation yog lub luag haujlwm tseem ceeb ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRC (Cov duab ntxiv 2(b)). Peb kuj tau txais 44 nodes thiab 125 npoo hauv PPI tes hauj lwm hauv cov neeg mob KICH (Cov duab ntxiv 2(c)). VEGFA thiab nws cov noob nyob sib ze muaj cov haujlwm hauv qab no hauv cov neeg mob KICH: O-glycan ua, Golgi lumen, b protein O-linked glycosylation, kev saib xyuas cov txheej txheem ntawm epithelial, thiab lub koom haum nruab nrab ntawm cov filament cytoskeleton (Ntxiv daim duab 2(d)). Tsis tas li ntawd, 30 nodes thiab 57 npoo tau txais hauv PPI tes hauj lwm hauv cov neeg mob nrog KIRP (Cov Duab Ntxiv 2(e)). Kev loj hlob ntawm cov leeg nqaij, kev sib txawv ntawm cov leeg nqaij, kev loj hlob ntawm cov nqaij leeg, thiab kev loj hlob ntawm cov txheej txheem ntawm cov leeg nqaij yog cov haujlwm tseem ceeb ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRP (Cov duab ntxiv 2(f)). VEGFA txuas nrog nws cov noob nyob sib ze rau hauv kev sib koom ua ke sib koom ua ke los ntawm kev sib tham, kev sib cuam tshuam ntawm lub cev, kwv yees sib koom cov protein ntau, thiab kev sib koom ua ke (Cov duab ntxiv 2(b) rau (f))

GO thiab KEGG pathway enrichment analysisGO muaj nuj nqi thiab KEGG txoj hauv kev txhim kho kev txheeb xyuas ntawm VEGFA thiab 50 qhov hloov pauv cov noob nyob sib ze hauv cov neeg mob RCC tau tshawb xyuas siv Metascape software. Peb cov txiaj ntsig tau pom tias cov khoom siv cellular cuam tshuam nrog VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRC feem ntau koom nrog hauv qab daus daim nyias nyias, caveola, adherens hlws ris, phev ib feem, thiab contractile fiber ntau (Cov duab ntxiv 3(a)). Ntxiv mus, coronary vasculature morphogenesis, cardiomyocyte txoj kev loj hlob, kev tswj zoo ntawm axon extension, thiab heterophilic cell-cell adhesion ntawm plasma membrane cell adhesion molecules yog cov txheej txheem tseem ceeb ntawm kev nthuav qhia ntawm VEGFA thiab nws cov kev hloov pauv cov noob nyob sib ze hauv cov neeg mob KIRC (Supplementary F. 3 (b)). Lub zog molecular ntawm VEGFA thiab nws cov saum toj kawg nkaus 50 hloov cov noob nyob sib ze nyob rau hauv cov neeg mob nrog KIRC feem ntau suav nrog cov khoom siv hluav taws xob sib txuas ntxiv, cell adhesion molecule binding, thiab catalytic kev ua haujlwm, nrog rau ua haujlwm ntawm RNA (Cov duab ntxiv 3(c)). Txoj hauv kev KEGG ntawm VEGFA thiab nws cov noob nyob sib ze hauv KIRC feem ntau koom nrog AGE-RAGE teeb liab txoj hauv kev hauv kev mob ntshav qab zib thiab PI3K-Akt signaling pathway (Cov duab ntxiv 3(d)). Golgi lumen, extracellular matrix, ATPase complex, thiab Z disc yog cellular Cheebtsam uas muaj feem xyuam rau kev qhia ntawm VEGFA thiab nws cov noob nyob sib ze rau cov neeg mob KICH (Cov duab ntxiv 3(e)). Tsis tas li ntawd, cov txheej txheem lom neeg tseem ceeb uas cuam tshuam nrog kev qhia ntawm VEGFA thiab nws cov 50 hloov pauv cov noob nyob sib ze hauv cov neeg mob KICH yog kev saib xyuas ntawm lub plab hnyuv epithelium, kev tswj tsis zoo ntawm lub koom haum cellular tivthaiv, thiab kho qhov txhab (Ntxiv daim duab 3(f)) . Cov haujlwm molecular ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KICH yog ATPase kev ua, actin filament binding, thiab protease binding (Cov duab ntxiv 3(g)). ATP-binding cassette (ABC) thauj neeg thiab tib neeg T-cell leukemia kab mob 1 tau koom nrog hauv KEGG txoj kev tsom xam ntawm VEGFA thiab nws cov 50 hloov pauv cov noob nyob sib ze hauv cov neeg mob KICH (Cov duab ntxiv 3(h)). Tsis tas li ntawd, cov khoom siv ntawm tes muaj feem xyuam nrog VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRP feem ntau koom nrog hauv Golgi lumen thiab centriole (Cov duab ntxiv 3(I)). Ntxiv mus, cov ntaub so ntswg homeostasis, myeloid cell homeostasis, O-glycan ua thiab cellular teb rau lipids yog cov txheej txheem tseem ceeb lom neeg koom nrog hauv kev qhia ntawm VEGFA thiab nws cov hloov pauv cov noob nyob sib ze hauv cov neeg mob KIRP (Cov duab ntxiv 3(j)). Cov kev ua haujlwm molecular ntawm VEGFA thiab nws cov 50 hloov pauv cov noob nyob sib ze hauv cov neeg mob nrog KIRP feem ntau suav nrog kev ua haujlwm ntawm coactivator, cysteine-type peptidase kev ua, thiab calmodulin-binding (Ntxiv daim duab 3(k)). Vibrio cholerae kab mob, dilated cardiomyopathy, thiab tib neeg cytomegalovirus kab mob tau koom nrog hauv KEGG txoj hauv kev tsom xam ntawm VEGFA thiab nws cov noob nyob sib ze hloov pauv hauv cov neeg mob KIRP (Cov duab ntxiv 3(l)).

CISTANCHE yuav txhim kho lub raum / raum kab mob

Kev hloov pauv cov hom phiaj ntawm VEGFA hauv cov neeg mob RCCMuaj peev xwm hloov pauv tau, kinase, thiab miRNA lub hom phiaj ntawm VEGFA hauv cov neeg mob RCC tau txais kev siv TRRUST software (Table 1). Hypoxia-inducible factor 1 alpha subunit (HIF1A), transcription factor AP-2 alpha (TFAP2A), thiab estrogen receptor 1 (ESR1) yog cov ntsiab lus tseem ceeb uas cuam tshuam nrog lub network ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRC. (P < 0="" 05).="" rora,="" setd2,="" vegfa,="" thiab="" vhl="" tau="" tswj="" cov="" noob="" ntawm="" hif1a.="" tsis="" tas="" li="" ntawd,="" tfap2a="" tswj="" cov="" haujlwm="" ntawm="" adra1a="" thiab="" vegfa.="" nr5a2="" thiab="" vegfa="" tau="" tswj="" cov="" noob="" ntawm="" esr1.="" txawm="" li="" cas="" los="" xij,="" qhov="" tseem="" ceeb="" ntawm="" kev="" hloov="" pauv="" lub="" hom="" phiaj="" koom="" nrog="" hauv="" lub="" network="" ntawm="" vegfa="" thiab="" nws="" cov="" noob="" nyob="" sib="" ze="" yog="" cov="" teeb="" liab="" transducer="" thiab="" activator="" ntawm="" transcription="" 3="" (stat3),="" nuclear="" factor="" ntawm="" kappa="" lub="" teeb="" polypeptide="" noob="" enhancer="" hauv="" b-cells="" 1="" (nfkb1),="" thiab="" homeodomain.="" interacting="" protein="" kinase="" 2="" (hipk2)="" hauv="" cov="" neeg="" mob="" kich="" (p="">< 0.01).="" cov="" noob="" tswj="" hwm="" ntawm="" stat3="" yog="" a2m,="" muc4,="" muc5b,="" tp53,="" thiab="" vegfa.="" ntxiv="" rau,="" nfkb1="" tswj="" cov="" haujlwm="" ntawm="" a2m,="" muc5b,="" muc6,="" tnc,="" tp53,="" thiab="" vegfa.="" tp53="" thiab="" vegfa="" tau="" tswj="" cov="" noob="" ntawm="" hipk2.="" tsis="" tas="" li="" ntawd,="" forkhead="" box="" o3="" (foxo3),="" tfap2a="" (ua="" kom="" muaj="" txiaj="" ntsig="" zoo-binding="" protein="" 2="" alpha),="" thiab="" v-ets="" erythroblastosis="" virus="" e26="" oncogene="" homolog="" 1="" (ets1)="" yog="" qhov="" tseem="" ceeb="" ntawm="" cov="" hom="" phiaj="" ntawm="" vegfa="" thiab="" nws="" cov="" noob="" nyob="" sib="" ze="" hauv="" cov="" neeg="" mob="" kirp="" (="" p=""><0.05). ntxiv="" mus,="" bcl2l11="" thiab="" vegfa="" tau="" tswj="" cov="" noob="" ntawm="" foxo3.="" tsis="" tas="" li="" ntawd,="" tfap2a="" tswj="" cov="" haujlwm="" ntawm="" muc4="" thiab="" vegfa.="" casp1="" thiab="" muc4="" yog="" cov="" noob="" tswj="" los="" ntawm="">

Kinase thiab miRNA lub hom phiaj ntawm VEGFA hauv cov neeg mob RCC Peb kuj tau txais peb lub hom phiaj kinase thiab miRNA lub hom phiaj ntawm VEGFA network nrog LinkedOmics (Table 2). VEGFA miRNA-target network hauv KIRC tau txuam nrog ATAAGCT MIR-21 (P < 0.05).="" ntxiv="" mus,="" kinase="" lub="" hom="" phiaj="" ntawm="" vegfa="" yog="" kinase="" atm="" hauv="" cov="" neeg="" mob="" kich="" (p="">< 0="" 05).="" tsis="" tas="" li="" ntawd,="" kinase="" cdk1="" thiab="" kinase="" aurkb="" yog="" lub="" hom="" phiaj="" kinase="" ntawm="" vegfa="" hauv="" cov="" neeg="" mob="" kirp="" (p=""><0.05). mirna="" lub="" hom="" phiaj="" ntawm="" vegfa="" yog="" (tcgatgg)="" mir-213,="" (tctgatc)="" mir-383,="" thiab="" (caggtcc)="" mir-492="" hauv="" cov="" neeg="" mob="" kirp="" (p=""><>

Kev sib raug zoo ntawm cov noob qhia txawv txawv thiab VEGFA qhia hauv cov neeg mob RCCPeb tau txais mRNA sequencing cov ntaub ntawv ntawm 533 cov neeg mob nrog KIRC hauv TCGA database ntawm LinkedOmics. Raws li pom nyob rau hauv Ntxiv daim duab 4(a), 20,158 noob tau ze ze rau VEGFA. Ntawm lawv, 11,417 thiab 8741 noob tau pom muaj kev sib raug zoo thiab tsis zoo, feem, nrog VEGFA qhia. Tsis tas li ntawd, 50 cov noob tseem ceeb tau zoo thiab tsis zoo cuam tshuam nrog VEGFA qhia hauv cov neeg mob KIRC (P <0.05) (cov="" duab="" ntxiv="" 4(b)="" thiab="" (c)).="" ntxiv="" mus,="" qhov="" kev="" qhia="" ntawm="" vegfa="" tau="" muaj="" kev="" sib="" raug="" zoo="" nrog="" notch4="" (pearson="" correlation="" coefficient="0.7023," p="2.076e–80)" (cov="" duab="" ntxiv="" 5(a)),="" gpr4="" (pearson="" correlation{="" {19}}.702,="" p="2.63e–80)" (cov="" duab="" ntxiv="" 5(b)),="" thiab="" trib2="" (pearson="" correlation="0.6972," p="8.902e–79" )="" (cov="" duab="" ntxiv="" 5(c))="" cov="" lus="" qhia.="" tsis="" tas="" li="" ntawd,="" peb="" tau="" soj="" ntsuam="" mrna="" sequencing="" cov="" ntaub="" ntawv="" ntawm="" 66="" tus="" neeg="" mob="" nrog="" kich="" hauv="" tcga="" database="" thiab="" pom="" tias="" 19,216="" cov="" noob="" muaj="" feem="" cuam="" tshuam="" nrog="" vegfa="" qhia.="" ntawm="" lawv,="" 8820="" thiab="" 10,396="" cov="" noob="" tau="" pom="" muaj="" kev="" sib="" raug="" zoo="" thiab="" tsis="" zoo,="" feem,="" nrog="" vegfa="" qhia="" (cov="" duab="" ntxiv="" 4(d)).="" peb="" kuj="" tau="" txheeb="" xyuas="" 50="" cov="" noob="" tseem="" ceeb="" uas="" muaj="" qhov="" zoo="" thiab="" tsis="" zoo="" cuam="" tshuam="" nrog="" vegfa="" qhia="" hauv="" cov="" neeg="" mob="" kich="" (cov="" duab="" ntxiv="" 4(e)="" thiab="" (f)).="" tsis="" tas="" li="" ntawd,="" vegfa="" qhia="" tau="" zoo="" txuam="" nrog="" ckmt2="" (pearson="" correlation="0.6474," p="4.236e–9)" (cov="" duab="" ntxiv="" 5(d)),="" rragd="" (pearson="" correlation="0" .6279,="" p="1.673e–8)" (cov="" duab="" ntxiv="" 5(e)),="" thiab="" ppargc1a="" (pearson="" correlation="0.6086," p="5.93e–8)" (cov="" duab="" ntxiv="" 5(f))="" cov="" lus="" qhia.="" thaum="" kawg,="" peb="" txheeb="" xyuas="" mrna="" sequencing="" cov="" ntaub="" ntawv="" ntawm="" 290="" cov="" neeg="" mob="" nrog="" kirp="" hauv="" tcga="" database.="" tsis="" tas="" li="" ntawd,="" 20,023="" cov="" noob="" tau="" zoo="" cuam="" tshuam="" nrog="" vegfa="" qhia.="" ntawm="" lawv,="" 11,130="" thiab="" 8893="" cov="" noob="" tau="" pom="" muaj="" kev="" sib="" raug="" zoo="" thiab="" tsis="" zoo,="" feem,="" nrog="" vegfa="" qhia="" vegfa="" (cov="" duab="" ntxiv="" 4(g)).="" peb="" tau="" txheeb="" xyuas="" 50="" cov="" noob="" tseem="" ceeb="" uas="" muaj="" qhov="" zoo="" thiab="" tsis="" zoo="" cuam="" tshuam="" nrog="" vegfa="" qhia="" hauv="" cov="" neeg="" mob="" nrog="" kirp="" (cov="" duab="" ntxiv="" 4(h)="" thiab="" (i)).="" qhov="" kev="" qhia="" ntawm="" vegfa="" tau="" zoo="" txuam="" nrog="" flt1="" (pearson="" correlation="0.8184," p="2.909e–71)" (cov="" duab="" ntxiv="" 5(g)),="" c6orf223="" (pearson="" correlation="0." 7779,="" p="4.606e–60)" (cov="" duab="" ntxiv="" 5(h)),="" thiab="" esm1="" (pearson="" correlation="0.7602," p="6.983e–56)" (cov="" duab="" ntxiv="" 5="" (i))="" cov="" lus="">

CISTANCHE yuav txhim kho lub raum / raum mob

Immune cell infiltration thiab VEGFA qhia hauv cov neeg mob RCCTxhawm rau nthuav qhia ntxiv txog kev sib raug zoo ntawm kev tiv thaiv kab mob hauv lub cev thiab VEGFA kev qhia hauv cov neeg mob RCC, peb tau tshuaj xyuas qhov sib txheeb ntawm lub cev tiv thaiv kab mob thiab VEGFA qhia siv TIMER software. Kev qhia theem ntawm VEGFA hauv cov neeg mob KIRC tau zoo cuam tshuam nrog kev nkag mus ntawm CD8 ntxiv rau T hlwb (Cor=0.197, P=3.36e-5), CD4 ntxiv rau T hlwb ( Cor= 0.301, P=4.41e-11), thiab neutrophils (Cor =0.223, P= 1.44e -6) (Cov duab ntxiv 6(a)). Tsis tas li ntawd, peb tau txheeb xyuas qhov kev sib raug zoo ntawm kev tiv thaiv kab mob hauv lub cev thiab kev qhia VEGFA hauv cov neeg mob KICH. Infiltration B (Cor{18}}.349, P=4.39e-3), CD8 plus T (Cor{24}}.398, P=1.03e -5), thiab dendritic hlwb (Cor=0.253, P=4.18e-2) tau muaj txiaj ntsig zoo nrog kev qhia ntawm VEGFA (Cov duab ntxiv 6(b)) . Thaum kawg, theem kev qhia ntawm VEGFA hauv cov neeg mob KIRC tau zoo cuam tshuam nrog kev nkag mus ntawm B (Cor{35}}.16, P=1.04e-2), CD8 ntxiv rau T (Cor{ {41}}.179, P=0.384e-3), thiab CD4 plus T cells (Cor=0.157, P=1.14e-2 ) (Cov duab ntxiv 6(c)). Txawm li cas los xij, macrophage infiltration (Cor=-0.226, P=3.22e-4) tau cuam tshuam tsis zoo nrog VEGFA qhia (Cov duab ntxiv 6(c)).

Kev sib tham

VEGFA, ib tug tswv cuab ntawm VEGF tsev neeg, yog ib qho tseem ceeb cytokine thiab ib tug ua inducer ntawm angiogenesis.22 Preclinical kev tshawb fawb tau qhia tias VEGFA yog overexpressed nyob rau hauv cov neeg mob nrog RCC.23,24 Txawm li cas los xij, theem qhia ntawm VEGFA hauv cov neeg mob RCC tseem muaj teeb meem. .25,26 Tumor angiogenesis plays lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm RCC. Cov tshuaj tsom rau cov qog angiogenesis tau siv rau hauv kev kho mob ntawm RCC rau ze li 20 xyoo.27 Txawm li cas los xij, cov kev kho mob ntawm cov tshuaj no tseem tsis zoo, thiab lawv cov kev mob tshwm sim yuav tsum tau txo. Peb tau nrhiav los nthuav tawm cov kev cai ntawm cov noob caj noob ces, tus nqi prognostic, thiab lub hom phiaj kwv yees ntawm VEGFA hauv cov neeg mob RCC.

Tsis tas li ntawd, peb tau tshawb nrhiav qib kev qhia ntawm VEGFA thiab kev sib raug zoo ntawm qhov sib txawv ntawm VEGFA thiab theem pathological hauv cov neeg mob RCC. VEGFA qhia tau raug kho rau cov neeg mob KIRC thiab KICH ntau dua li cov tib neeg ib txwm muaj. Txawm li cas los xij, cov neeg mob nrog KIRP tau txo qis VEGFA qhia. Cov kev tshawb pom no zoo ib yam li cov kev tshawb pom yav dhau los hauv cov neeg mob KIRC, KICH, thiab KIRP, 26,28 thiab tsis sib haum nrog cov kev tshawb pom yav dhau los hauv cov neeg mob KICH.25 Peb tau sim piav qhia qhov tsis sib haum xeeb los ntawm kev hloov pauv noob thiab txhawb nqa methylation hauv cov neeg mob. RCC. Peb pom tias kev hloov pauv caj ces tshwm sim hauv 4 feem pua, 8 feem pua, thiab 4 feem pua ​​​​ntawm cov neeg mob KIRC, KICH, thiab KIRP, feem. Ntxiv mus, cov qib txhawb methylation ntawm VEGFA qis dua hauv cov neeg mob uas muaj KIRC theem sib txawv dua li cov neeg noj qab haus huv; Hauv qhov sib piv, cov qib txhawb methylation ntawm VEGFA tau siab dua hauv cov neeg mob nrog theem 1 KIRP. Txawm li cas los xij, tsis muaj qhov sib txawv ntawm qib txhawb methylation ntawm VEGFA tau pom ntawm cov neeg mob KICH thiab cov neeg noj qab haus huv. Yog li, peb xav tias kev hloov pauv caj ces thiab methylation ntawm VEGFA tuaj yeem yog qhov ua rau ntawm VEGFA sib txawv hauv cov neeg mob RCC. VEGFA qhia thiab KIRC thiab KIRP pathological theem. Tsis tas li ntawd, kev muaj sia nyob ntawm cov neeg mob nrog KIRP muaj qib VEGFA qis dua tau ntev dua li cov neeg mob KIRP muaj qib VEGFA siab. Qhov tseem ceeb, peb tau txais cov txiaj ntsig sib txawv tom qab 100 lub hlis hauv cov neeg mob KIRP raws li kab mob tsis muaj sia nyob nkhaus. Yog li, VEGFA qhia theem yuav yog ib qho kev ntsuas ntsuas hauv cov neeg mob KIRP. Qee qhov kev tshawb fawb tau qhia tias VEGF kev qhia yuav yog qhov tseem ceeb ntawm RCC siab heev. Kev kuaj pom ntawm CD147/VEGF co-expression tuaj yeem pab kwv yees qhov kev cia siab ntawm cov neeg mob uas muaj RCC.29

Ntxiv mus, 50 feem ntau nquag VEGFA cov noob nyob sib ze tau hloov pauv hauv cov neeg mob RCC raws li cov zaus hauv qab no: Ntau dua lossis sib npaug rau 11.11 feem pua ​​(KIRC), Ntau dua lossis sib npaug li 20 feem pua ​​(KICH), thiab Ntau dua lossis sib npaug rau 9.09 feem pua ​​(KIRP). Tom qab ntawd peb tshawb nrhiav cov kev sib cuam tshuam thiab kev ua haujlwm ntawm VEGFA thiab nws cov noob nyob sib ze; cov no tau pom tias muaj kev sib txuas sib txuas thiab nruj. Hauv cov neeg mob KIRC, cov noob no tau koom nrog hauv cov protein methylation. Txawm li cas los xij, hauv cov neeg mob KICH, VEGFA cov noob nyob sib ze ua haujlwm hauv cov protein glycosylation thiab kev saib xyuas ntawm tes. Tsis tas li ntawd, VEGFA cov noob nyob sib ze tau cuam tshuam nrog cov leeg nqaij fiber ntau thiab kev sib txawv ntawm cov neeg mob KIRP. Kev hloov pauv hauv cov protein methylation yog qhov tseem ceeb rau kev txiav txim siab txoj hmoo ntawm tes thiab kev loj hlob ntawm tes. Protein methylation tshwm sim feem ntau nyob rau sab chains ntawm Lys thiab Arg residues.30 Piv txwv li, histone methylation feem ntau pom nyob rau hauv cov qog nqaij hlav nrog methylation ntawm Lys thiab Arg residues.31 Aberrant methylation thiab O-glycosylation yog ib qho kev hloov kho qog nqaij hlav epigenetic. Aberrant O-glycosylation pab txhawb kev loj hlob ntawm cov qog nqaij hlav los ntawm kev ncaj qha induction ntawm oncogenic zog nyob rau hauv cov qog nqaij hlav cancer.32 KIRP yog ib tug malignant qog ntawm lub qog.lub raum parenchyma having a papillary or tubular papillary structure with a fibrous vessel axis. KIRP occurrence may be associated with the occurrence of RCCs with angioleiomyoma-like stroma (also known as smooth muscle or leiomyoma stroma), owing to the substantial similarity of their immunohistochemical phenotypes.33 The above evidence reveals that VEGFA neighboring genes might impact the occurrence and progression of RCC.

CISTANCHE yuav txhim kho lub raum / raum mob ntshav qab zib

Tsis tas li ntawd, GO enrichment tsom xam tau qhia tias lub luag haujlwm ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob KIRC feem ntau cuam tshuam nrog cell adhesion molecule binding thiab catalytic kev ua haujlwm, nrog rau kev ua haujlwm ntawm RNA. Lub epithelial cell adhesion molecule (EPCAM) tsis ntev los no tau txais kev saib xyuas raws li tus neeg sib tw cov protein rau kev kuaj mob, kev kuaj mob, thiab kev kho mob ntawm ntau yam qog. EPCAM yog ib qho kev ywj pheej prognostic molecular marker nyob rau hauv RCC, thiab tej zaum yuav muab cov ntaub ntawv auxiliary rau prognosis zoo dua.34 Peb pom tias ATPase kev ua, actin filament binding, thiab protease binding yog lub molecular functions ntawm VEGFA thiab nws cov noob nyob ze rau cov neeg mob KICH. Mitochondrial morphological thiab kev ua haujlwm hloov pauv tau paub tias tshwm sim hauv cov neeg mob KICH35; Kev hloov pauv kev ua ATPase tuaj yeem yog qhov muaj peev xwm ua kom muaj kab mob. Txawm li cas los xij, cov kev tshawb fawb ntxiv yuav tsum tau ua kom paub meej tias cov txheej txheem no. Hauv peb txoj kev tshawb fawb, cov haujlwm molecular ntawm VEGFA thiab nws cov hloov pauv cov noob nyob sib ze hauv cov neeg mob nrog KIRP feem ntau suav nrog kev ua haujlwm ntawm coactivator, cysteine-type peptidase kev ua, thiab calmodulin-binding. Calmodulin yog ib qho ubiquitous intracellular calcium-binding protein qhia tau hais tias txuam nrog lub voj voog ntawm tes. Cov neeg mob nrog RCC paub tias muaj kev sib raug zoo ntawm cov qog calmodulin cov ntsiab lus thiab cov qog loj hlob tuaj.36 Peb pom tias AGE-RAGE qhia txoj hauv kev hauv cov mob ntshav qab zib, PI3K-Akt signaling pathway, ABC transporter action, thiab tib neeg T-cell leukemia kab mob. 1 tus kab mob tau koom nrog hauv KEGG txoj kev tsom xam ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob RCC; Cov txheej txheem no muaj feem cuam tshuam nrog kev mob qog noj ntshav thiab kev loj hlob.37 Yog li, tswj cov kev taw qhia no tej zaum yuav yog lub hom phiaj kho RCC.

Peb kuj tau txheeb xyuas cov hom phiaj thiab cov tswj hwm ntawm VEGFA hauv cov neeg mob RCC. Peb thawj zaug tshawb nrhiav lub hom phiaj ntawm kev hloov pauv ntawm VEGFA thiab nws cov noob nyob sib ze hauv cov neeg mob RCC, thiab pom tias HIF1A, TFAP2A, thiab ESR1 yog qhov tseem ceeb ntawm cov neeg mob KIRC. HIF-1 yog ib qho tseem ceeb gene regulator koom nrog hauv cellular teb rau hypoxia. HIF-1 overexpression yog txuam nrog RCC pathogenesis; Tsis tas li ntawd, kev ua haujlwm polymorphism ntawm HIF1A tuaj yeem ua rau muaj kev cuam tshuam rau RCC, thiab HIF1A polymorphism tuaj yeem cuam tshuam rau RCC rov tshwm sim, kev vam meej, thiab kev ciaj sia.38 Txawm li cas los xij, TFAP2A thiab ESR1 tsis tau tshaj tawm rau cov neeg mob RCC. Peb kuj pom tias STAT3, NFKB1, thiab HIPK2 tau tswj hwm qhov tseem ceeb hauv cov neeg mob KICH. STAT3 cov proteins yog qhov tseem ceeb ntawm cov ntaub ntawv hloov pauv uas ua rau muaj qhov txawv txav ntawm ntau yam malignancies, suav nrog RCC.39 STAT3 inhibition tuaj yeem cuam tshuam RCC cell migration thiab ntxeem tau.40

NFKB1 muaj feem xyuam rau cov kab mob ntawm ntau cov qog nqaij hlav, suav nrog RCC. Functional NFKB1 txhawb nqa polymorphism yog txuam nrog kev pheej hmoo ntawm RCC.41 HIPK2 ua lub luag haujlwm tshwj xeeb hauv kev tswj hwm ntawm cell apoptosis thiab kev loj hlob, nrog rau kev kho DNA puas thiab lwm yam txheej txheem yooj yim; Yog li, HIPK2 tau txais kev saib xyuas ntxiv. FOXM1 phosphorylation los ntawm HIPK2 txhawb nqa kev ua haujlwm transcriptional thiab FOXM1 cell proliferation nyob rau hauv cov neeg mob nrog RCC, uas tej zaum yuav muaj peev xwm RCC kho mechanism.42 Hauv peb txoj kev tshawb fawb, FOXO3, TFAP2A, thiab ETS1 tau pom tias yog qhov tseem ceeb ntawm cov hom phiaj ntawm VEGFA thiab nws cov noob nyob sib ze. hauv cov neeg mob KIRP. FOXO3-kev kho mob phosphofructokinase-M qhia inhibits RCC cell loj hlob, tsiv teb tsaws, thiab ntxeem tau, 43 FOXO3 tuaj yeem siv los ua biomarker tshiab raws li lub hom phiaj kho mob tshiab hauv RCC kev kho mob.44 ETS1 zoo li yog qhov tseem ceeb ntawm kev hloov pauv hauv cov cellular. matrix remodeling thaum lub sij hawm angiogenesis; Tej zaum nws yuav koom nrog RCC angiogenesis.45 Peb tau tshawb nrhiav ntxiv VEGFA-txuas nrog kinase lub hom phiaj (ATM hauv KICH, nrog rau CDK1 thiab AURKB hauv KIRP) thiab VEGFA-txuas nrog miRNA lub hom phiaj (MIR-21 hauv KIRC; MIR{ {23}}, MIR-383, thiab MIR-492 hauv KIRP). Ntau xyoo dhau los, ntau cov kev tshawb fawb tau pom tias cov protein kinase mob los yog kev hloov pauv ua lub luag haujlwm ua rau mob qog noj ntshav. Kev tshawb fawb txog mob qog noj ntshav tau qhia txog lub luag haujlwm tseem ceeb ntawm ntau cov protein kinases hauv tib neeg cov qog nqaij hlav qog nqaij hlav thiab mob qog noj ntshav, ua rau cov molecules muaj txiaj ntsig zoo rau cov kev kho mob tshiab.46 Kinase inhibitors tau hloov kho cov kev kho mob ntawm qee hom qog nqaij hlav malignant.47 miRNAs yog ib chav kawm ntawm cov tsis- coding RNAs uas ua lub luag haujlwm tseem ceeb hauv kev tswj hwm ntawm noob caj noob ces. miRNA inhibitors txo qhov kev qhia ntawm cov noob hom phiaj los ntawm kev cuam tshuam nrog 3′ thaj tsam tsis tau txhais ntawm cov hom phiaj. Lawv lub luag haujlwm tseem ceeb hauv kev tswj cov qog nqaij hlav qog nqaij hlav thiab kev qhia ntawm oncogene txhim kho lawv lub luag haujlwm hauv cov qog nqaij hlav.48 Qhov kev tshawb pom ntawm miRNA lub hom phiaj tuaj yeem piav qhia txog cov txheej txheem hauv qab ntawm cov qog nqaij hlav thiab kev txhim kho tshuaj tiv thaiv kab mob.49 Txoj kev tshawb no muab cov ntaub ntawv siv thiab qhia txog qhov tseem ceeb ntawm kev nthuav dav ntxiv. Kev tshuaj xyuas ntawm cov xwm txheej tswj hwm, kinases, thiab miRNAs raws li lub hom phiaj kho mob rau RCC.

Peb tshawb nrhiav qhov sib txheeb ntawm qhov sib txawv ntawm cov noob thiab VEGFA qhia hauv cov neeg mob RCC. Ntau tshaj 10,000 cov noob tau zoo thiab tsis zoo cuam tshuam nrog VEGFA qhia hauv cov neeg mob RCC. Ntawm lawv, cov noob uas muaj kev sib raug zoo tshaj plaws nrog VEGFA tau pom hauv cov neeg mob RCC: NOTCH4, GPR4, thiab TRIB2 hauv KIRC; CKMT2, RRAGD, thiab PPARGC1A hauv KICH; thiab FLT1, C6orf223, thiab ESM1 hauv KIRP. Txawm li cas los xij, kev tsom mus rau cov noob qog noj ntshav no tuaj yeem muab kev kho mob ntxiv rau RCC. Immunoinfifiltration ntawm RCC yog ze ze rau kev soj ntsuam kuaj mob.50 Kev thauj mus los ntawm lub cev tiv thaiv kab mob mus rau qhov chaw mob qog noj ntshav tshwm sim feem ntau ntawm cov hlab ntsha. Raws li qhov xav tau, peb pom tias VEGFA qhia hauv cov neeg mob RCC tau zoo cuam tshuam nrog kev tiv thaiv kab mob hauv lub cev, suav nrog CD8 ntxiv rau T hlwb, CD4 ntxiv rau T hlwb, macrophages, neutrophils, thiab dendritic hlwb. Peb cia siab tias yuav txhim kho lub cev tiv thaiv kab mob hauv lub cev ntawm RCCs los ntawm kev tsim cov tshuaj ua haujlwm ntawm VEGFA lossis VEGFA ntsig txog cov hom phiaj. Hauv kev xaus, los ntawm kev tshawb nrhiav qib kev qhia thiab kev tswj cov noob caj noob ces ntawm VEGFA hauv cov neeg mob RCC, peb tau muab kev nkag siab ntau ntxiv rau kev kawm thiab kev kho mob ntawm RCC. Tsis tas li ntawd, peb tau txheeb xyuas cov hom phiaj kho mob tshiab thiab cov kab mob prognostic biomarkers rau kev kwv yees qhov tseeb ntawm RCC tus neeg mob ciaj sia.