{"id":19837,"date":"2022-09-15T11:59:00","date_gmt":"2022-09-15T14:59:00","guid":{"rendered":"https:\/\/mindthegraph.com\/blog\/?p=19837"},"modified":"2023-03-20T09:54:50","modified_gmt":"2023-03-20T12:54:50","slug":"cutaneous-and-acral-melanoma","status":"publish","type":"post","link":"https:\/\/mindthegraph.com\/blog\/sl\/kozni-in-akralni-melanom\/","title":{"rendered":"Pregled raziskav: Ko\u017eni in akralni melanom"},"content":{"rendered":"

\u017de desetletja v nekaterih populacijah poro\u010dajo o pove\u010dani pojavnosti melanoma po vsem svetu. Novotvorba melanocitov v ko\u017ei, sluznici ali uvei je znana kot melanom. Kljub 5% zastopanosti med vsemi ko\u017enimi malignomi je odgovoren za ve\u010d kot 75% vseh smrti zaradi ko\u017enega raka.\u00a0<\/p>\n\n\n\n

\u010ceprav je pozitivna povezava med izpostavljenostjo UV-\u017earkom in razvojem melanoma dobro znana, so epigenetski mehanizmi, ki so v ozadju, v tkivih \u010dlove\u0161kega melanoma v veliki meri neraziskani. V tem \u010dlanku bo obravnavan prognosti\u010dni dejavnik raka, povezan s patobiologijo in izpostavljenostjo ultravijoli\u010dnim \u017earkom, skupaj z avtorjevimi spoznanji o omenjeni temi. <\/p>\n\n\n\n

Cilj \u0161tudije<\/h2>\n\n\n\n

Z uporabo dveh neodvisnih kohort bolnikov s ko\u017enim melanomom \u017eelijo odkriti in potrditi spremembe metilacije v celotnem genomu, povezane z mutacijami UV-\u017earkov. Klju\u010dni cilj je raziskati diagnosti\u010dni potencial metilomov DNK v primerjavi s transkriptomi in integriranimi metilom-transkriptomi za razlikovanje med ko\u017enimi melanomi z UV-mutanti in brez UV-mutantov. <\/p>\n\n\n\n

Z uporabo integrativnega pristopa OMIC so majhne nukleotidne razli\u010dice (SNV) in razli\u010dice \u0161tevila kopij (CNV) prednostno razvr\u0161\u010denih razli\u010dno metiliranih genov ocenjene glede potenciala za povzro\u010ditelja raka. Ta raziskava je dodatno podprta z drugo, ki preu\u010duje, ali lahko metilomi DNK razlikujejo patolo\u0161ke in z UV-sevanjem povezane razlike med vidnimi razli\u010dicami melanoma, ki so povezane z izpostavljenostjo UV-sevanju (ko\u017eni melanom), in tistimi, ki niso (akralni melanom). Shema v dokumentu prikazuje cilj in potek \u0161tudije. Grafi\u010dni prikaz je bil ustvarjen z uporabo Mind the Graph<\/a><\/strong>.<\/p>\n\n\n\n

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Podroben pregled \u0161tudije<\/h2>\n\n\n\n

V klini\u010dnih biolo\u0161kih vzorcih je UV sevanje (UV) povezano s ko\u017enim melanomom, vendar epigenetski mehanizmi, ki so podlaga za te mehanizme, \u0161e niso dolo\u010deni. V to \u0161tudijo je bila vklju\u010dena multietni\u010dna kohorta 112 celic ko\u017enega melanoma za klini\u010dno profiliranje, profiliranje epigenoma (metiloma DNK), genoma in transkriptoma. V tej \u0161tudiji so opredelili spremembe, ki jih povzro\u010di UV-\u017earek, v imunolo\u0161kih in regulatornih poteh, ki so lahko dejavniki nastanka raka pri razli\u010dnih OMIK-ih.<\/p>\n\n\n\n

Poleg tega, da je gen TAPBP (Tap binding protein gene) najbolj kriti\u010dno vpleten v imunsko delovanje, je v njem tudi ve\u010d mest metilacije, spremenjenih z UV-\u017earki, ki so bila potrjena z usmerjenim sekvenciranjem, kar zagotavlja klini\u010dno uporabne prilo\u017enosti. MHC-I prek TAPBP, \u010dlana naddru\u017eine imunoglobulinov, sodeluje s transporterjem, povezanim s predelavo antigenov. Pri \u0161tevilnih rakavih obolenjih je bilo ugotovljeno zni\u017eanje regulacije beljakovine TAPBP (tapasin), ki se obnovi po izpostavljenosti citokinom.\u00a0<\/p>\n\n\n\n

To ka\u017ee, da je pomanjkljivo izra\u017eanje TAPBP lahko posledica disregulacije in ne strukturnih sprememb. Raziskovalci so ugotovili, da so ravni metilacije DNK TAPBP pomembno obratno sorazmerne s prepisovanjem in da se slednje spremeni zaradi izpostavljenosti UV-\u017earkom in ne zaradi patolo\u0161ke identitete melanoma. Pri ko\u017enih in akralnih melanomih, ki niso bili podvr\u017eeni UV-mutaciji, ni bilo ugotovljeno razli\u010dno metiliranje.<\/p>\n\n\n\n

Poleg ugotovitev o TAPBP so ugotovili, da so UV mutacije povezane z vrsto epigenetskih sprememb, ki vplivajo na metilom ko\u017enega melanoma. Rezultati ka\u017eejo, da bo morda treba ko\u017ene melanome, ne glede na to, ali so UV-mutantni ali ne, razvr\u0161\u010dati lo\u010deno, \u010deprav naj bi imeli enak patolo\u0161ki\/celi\u010dni izvor. Razlog za to je, da lahko epigenomska pokrajina, iz katere izhajajo, vsebuje tako ozna\u010devalce izpostavljenosti kot tudi celi\u010dne linije. <\/p>\n\n\n\n

V tej \u0161tudiji je bilo za vzorce ko\u017enega in akralnega melanoma uporabljenih ve\u010d zmogljivih tehnologij, vklju\u010dno z WGS, WES, sekvenciranjem RNA in profiliranjem celotnega metiloma DNK, skupaj z najsodobnej\u0161imi bioinformacijskimi orodji. Raziskovalci so uporabili javno dostopne podatke in jih dopolnili z novimi nabori podatkov, ki so vklju\u010devali ve\u010dje velikosti vzorcev, \u0161ir\u0161o genomsko pokritost, obse\u017ene fenotipske ocene, dobro ohranjene vzorce zamrznjenega tkiva ter oceno melanomov poleg ko\u017enih in etni\u010dnih skupin, ki niso Evropejci. <\/p>\n\n\n\n

Rezultati tega dela so bili naslednji<\/h2>\n\n\n\n

(1) Odkrivanje biomarkerjev, ki jih je mogo\u010de uporabiti za stratifikacijo tveganja za nastanek raka;<\/p>\n\n\n\n

(2) Izbolj\u0161ana klasifikacija tipov melanoma znotraj njih in med njimi; <\/p>\n\n\n\n

(3) opredelitev molekularnih dejavnikov, ki so lahko odgovorni za melanomagenezo in na katere je mogo\u010de usmeriti zdravljenje; <\/p>\n\n\n\n

(4) pove\u010danje znanja o patobiologiji melanoma za zmanj\u0161anje razlik med prebivalstvom.<\/p>\n\n\n\n

Ta \u0161tudija predstavlja na\u010drt za podobne raziskave genov in okolja pri drugih vrstah melanoma ter zajema tako pogoste kot manj pogoste melanome.<\/p>\n\n\n\n

U\u010dinkovitej\u0161i na\u010din sporo\u010danja natan\u010dnih znanstvenih informacij<\/h2>\n\n\n\n

Ta raziskovalni \u010dlanek je zelo zanimiv in enostaven za razumevanje, predvsem zaradi \u010dudovitih grafi\u010dnih ilustracij. Grafi so bili ustvarjeni z uporabo Mind the Graph<\/a> orodje. Grafi\u010dna ilustracija lahko bralcu koristi na razli\u010dne na\u010dine. Svojo raziskovalno raven lahko dvignete tako, da se brezpla\u010dno prijavite na Mind the Graph in preizkusite svojo prvo znanstveno sliko.

Ne pozabite si ogledati na\u0161ega \u010dlanka \"Znanstvena ilustracija: Klju\u010d do sveta vizualne znanosti<\/a>“. <\/p>\n\n\n\n

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Ustvarjanje u\u010dinkovitih znanstvenih figur v nekaj minutah<\/a><\/div>\n<\/div>\n\n\n\n
<\/div>","protected":false},"excerpt":{"rendered":"

V tem \u010dlanku bo obravnavan prognosti\u010dni dejavnik raka, povezan s patobiologijo in izpostavljenostjo ultravijoli\u010dnim \u017earkom, skupaj z avtorjevimi ugotovitvami.<\/p>","protected":false},"author":27,"featured_media":27204,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[956],"tags":[937,96,554,775],"yoast_head":"\nResearch Review: Cutaneous and Acral Melanoma<\/title>\n<meta name=\"description\" content=\"This article will discuss the prognostic cancer driver related to pathobiology and ultraviolet exposure along with the author's insights.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/mindthegraph.com\/blog\/sl\/kozni-in-akralni-melanom\/\" \/>\n<meta property=\"og:locale\" content=\"sl_SI\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" 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