{"id":2267,"date":"2021-09-20T09:27:45","date_gmt":"2021-09-20T07:27:45","guid":{"rendered":"https:\/\/www.newslab.sk\/glykany-ako-potencialny-biomarker-pri-nadorovej-transformacii-prostaty-systematicky-prehlad\/"},"modified":"2021-09-20T09:30:22","modified_gmt":"2021-09-20T07:30:22","slug":"glycans-as-potential-markers-in-malignant-prostate-transformation","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/glycans-as-potential-markers-in-malignant-prostate-transformation\/","title":{"rendered":"Glycans as potential markers in malignant prostate transformation"},"content":{"rendered":"

*A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens<\/strong><\/span><\/p>\n

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\u00davod<\/strong><\/p>\n

N\u00e1dory prostaty (PCa) predstavuj\u00fa v\u00fdznamn\u00fa skupinu onkologick\u00fdch ochoren\u00ed u mu\u017eov, pri\u010dom ich incidencia a mortalita v popul\u00e1cii neust\u00e1le narast\u00e1 vzh\u013eadom na predl\u017euj\u00facu sa stredn\u00fa d\u013a\u017eku \u017eivota. Uveden\u00fd trend potvrdzuj\u00fa aj \u00fadaje z Global Cancer Observatory (graf 1)<\/strong>, kde v r\u00e1mci predikcie incidencie odhaduj\u00fa n\u00e1rast novodiagnostikovan\u00fdch pr\u00edpadov v Slovenskej republike v roku 2040 na 3 614 oproti 2 724 pr\u00edpadom zaznamenan\u00fdm v roku 2018. Odhadovan\u00fd n\u00e1rast bude teda viac ako 32 %.<\/p>\n

PCa predstavuj\u00fa heterog\u00e9nnu skupinu chor\u00f4b a preto vznik\u00e1 ot\u00e1zka potreby viacer\u00fdch biomarkerov pri rozhodova- n\u00ed o strat\u00e9gii terapie. Glyk\u00e1ny sa ukazuj\u00fa ako s\u013eubn\u00e9 biomarkery n\u00e1dorovej transform\u00e1cie, pri\u010dom dostupn\u00e9 d\u00e1ta ukazuj\u00fa, \u017ee zmeny v glyk\u00f3me m\u00f4\u017eu by\u0165 n\u00e1pomocn\u00e9 pri stratifik\u00e1cii pacientov. Aberantn\u00e1 glykozyl\u00e1cia je typickou \u010drtou n\u00e1dorov\u00fdch buniek a glyk\u00e1ny asociovan\u00e9 s n\u00e1dorom m\u00f4\u017eu pom\u00f4c\u0165 identifikova\u0165 malignitu. V r\u00e1mci n\u00e1dorov prostaty nach\u00e1dzame \u0161irok\u00e9 spektrum alter\u00e1ci\u00ed glyk\u00e1nov, ako je glykozyl\u00e1cia prostatick\u00e9ho \u0161pecifick\u00e9ho antig\u00e9nu (PSA), zv\u00fd\u0161en\u00e1 sialyz\u00e1cia, fukozyl\u00e1cia jadra, zv\u00fd\u0161en\u00e1 O-GlcN-acyl\u00e1cia, zmeny galekt\u00ednov a proteoglyk\u00e1nov(1).<\/p>\n

Cie\u013eom tohto preh\u013eadov\u00e9ho \u010dl\u00e1nku je zhrnutie aktu\u00e1lnych poznatkov o glyk\u00e1noch ako potenci\u00e1lnych diagnostick\u00fdch a prognostick\u00fdch markeroch. V\u00fdsledky prebiehaj\u00faceho v\u00fdskumu nazna\u010duj\u00fa, \u017ee anal\u00fdza glyk\u00e1nov by mohla by\u0165 realizovan\u00e1 v bud\u00facnosti v tzv. liquid based minim\u00e1lne invaz\u00edvnych odberoch z mo\u010du, respekt\u00edve krvi pacienta. Ak sa preuk\u00e1\u017ee dostato\u010dn\u00e1 senzitivita a \u0161pecificita t\u00fdchto met\u00f3d, maj\u00fa potenci\u00e1l zjednodu\u0161i\u0165 diagnostiku n\u00e1dorov\u00fdch chor\u00f4b prostaty.<\/p>\n

Glyk\u00e1ny a ich postavenie v r\u00e1mci n\u00e1dorovej transform\u00e1cie<\/h2>\n

Glyk\u00e1ny hraj\u00fa k\u013e\u00fa\u010dov\u00fa \u00falohu v r\u00e1mci z\u00e1kladn\u00fdch bunkov\u00fdch molekul\u00e1rnych dejov vr\u00e1tane bunkovej signaliz\u00e1cie, ovplyv\u0148uj\u00fa invazivitu n\u00e1dorov\u00fdch buniek, metast\u00e1zovanie, imunomodul\u00e1ciu, angiogen\u00e9zu a interakcie s bunkov\u00fdm matrixom(1).<\/p>\n

Zmeny glykozyl\u00e1cie s\u00fa charakteristickou \u010drtou mal\u00edgnej transform\u00e1cie a progresie ochorenia. Je zn\u00e1me, \u017ee n\u00e1dorov\u00e9 bunky nes\u00fa v\u00fdrazne zmenen\u00e9 glyk\u00e1nov\u00e9 profily v porovnan\u00ed s nemal\u00edgnymi bunkami. Glykoprote\u00edny m\u00f4\u017eu ma\u0165 glyk\u00e1ny viazan\u00e9 na prote\u00edny prostredn\u00edctvom N-glykozyl\u00e1cie (tzv. N-glyk\u00e1ny, glyk\u00e1ny viazan\u00e9 na-NH2 of Asn) alebo prostredn\u00edctvom O-glykozyl\u00e1cie (tzv. O-glyk\u00e1ny, glyk\u00e1ny viazan\u00e9 na -OH of Ser\/Thr). Zmeny v glykozyl\u00e1cii s\u00fa \u010dasto v\u00fdsledkom pozmenenej aktivity glykozyltransfer\u00e1z a glykozid\u00e1z, \u010do je zrejm\u00e9 zo zast\u00fapenia glykokonjug\u00e1tov na bunk\u00e1ch n\u00e1- doru(3). \u010casto op\u00edsanou zmenou glykozyl\u00e1cie pri n\u00e1dorovej transform\u00e1cii je zv\u00fd\u0161en\u00e1 \u03b12,3-sialyz\u00e1cia a fukozyl\u00e1cia, hlavne fukozyl\u00e1cia jadra(2). Nejde v\u0161ak o jedin\u00e9 zmeny, vzh\u013eadom na variabilitu sacharidov\u00e9ho re\u0165azca m\u00f4\u017eu by\u0165 n\u00e1dorov\u00e9 vzory pomerne komplexn\u00e9.<\/p>\n

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PSA glykozyl\u00e1cia a sialyz\u00e1cia glyk\u00e1nov<\/h1>\n

PSA je glykoprote\u00edn produkovan\u00fd epiteli\u00e1lnymi bunkami prostaty. G\u00e9n pre PSA patr\u00ed do rodiny kalikre\u00ednov\u00fdch g\u00e9nov k\u00f3duj\u00facich ser\u00ednov\u00e9 prote\u00e1zy. V s\u00fa\u010dasnosti je tento marker pou\u017e\u00edvan\u00fd na detekciu a monitorovanie chor\u00f4b prostaty. Zv\u00fd\u0161en\u00e9 s\u00e9rov\u00e9 hladiny PSA s\u00fa sp\u00f4soben\u00e9 disrupciou membr\u00e1n postihnut\u00fdch prostatick\u00fdch buniek, resp. jeho zv\u00fd\u0161enou produkciou. V\u00e4\u010d\u0161ina epiteli\u00e1lnych buniek prostaty vr\u00e1tane hyperplastick\u00fdch a n\u00e1dorovo transformovan\u00fdch produkuje PSA. Preto s\u00e9rov\u00e9 hladiny PSA nemaj\u00fa dostato\u010dn\u00fa \u0161pecificitu a neoddiferencuj\u00fa zmeny prostaty sp\u00f4soben\u00e9 n\u00e1dorom, ben\u00edgnou hyperpl\u00e1ziou prostaty (BPH) \u010di prostatit\u00eddou, ke\u010f\u017ee pri v\u0161etk\u00fdch doch\u00e1dza k elev\u00e1cii hodn\u00f4t PSA v krvi(4).<\/p>\n

PSA je teda v\u0161eobecne pou\u017e\u00edvan\u00fd ako biomarker n\u00e1dorov prostaty, ktor\u00fd v\u0161ak m\u00e1 pre svoju n\u00edzku \u0161pecificitu z\u00e1rove\u0148 n\u00edzku prognostick\u00fa hodnotu. Viacer\u00e9 dostupn\u00e9 pr\u00e1ce sa zaoberaj\u00fa sk\u00faman\u00edm glykozylovan\u00fdch foriem PSA a ich asoci\u00e1ciou s n\u00e1dorovou transform\u00e1ciou. Cie\u013eom je n\u00e1js\u0165 vhodnej\u0161\u00ed marker na identifik\u00e1ciu agres\u00edvnych invaz\u00edvnych foriem PCa, respekt\u00edve odl\u00ed\u0161i\u0165 agres\u00edvne od indolentn\u00fdch foriem malign\u00edt.<\/p>\n

Celkovo bolo op\u00edsan\u00fdch vy\u0161e 50 glykoforiem PSA, ale iba niektor\u00e9 typy s\u00fa detegovan\u00e9 pri invaz\u00edvnych form\u00e1ch karcin\u00f3- mov. Realizovan\u00e9 v\u00fdskumy ukazuj\u00fa, \u017ee pr\u00e1ve komplexy PSA s naviazanou 2,3-kyselinou sialovou s\u00fa \u00fazko spojen\u00e9 s invaz\u00edvnymi formami n\u00e1dorov. V kombin\u00e1cii Prostate Health Index (PHI) a detekcie glykoforiem PSA s 2,3-kyselinou sialovou v kohorte 79 pacientov bola preuk\u00e1zan\u00e1 100 % senzitivita a 94,7 % \u0161pecificita pri odl\u00ed\u0161en\u00ed high-risk n\u00e1dorov od low-risk a ben\u00edgnych foriem(1).<\/p>\n

S\u00fa\u010dasn\u00fd v\u00fdskum sa zameriava pr\u00e1ve na identifik\u00e1ciu PCa biomarkerov z jednotliv\u00fdch izoforiem s cie\u013eom vyvin\u00fa\u0165 \u010do najpresnej\u0161iu metodiku testovania. V pr\u00e1ci Yoneyama a kol. publikovali v\u00fdvoj imunotestu na b\u00e1ze magnetick\u00fdch mikrogu\u013e\u00f4\u010dok s detekciou \u03b12,3-asociovanej sialyz\u00e1cie na vo\u013enej PSA (s2,3-PSA). Senzitivita, respekt\u00edve \u0161pecificita testu bola 95 %, respekt\u00edve 72 % napriek limit\u00e1cii \u0161t\u00fadie n\u00edzkym po\u010dtom zahrnut\u00fdch pacientov. V\u00fdsledky v\u0161ak ukazuj\u00fa, \u017ee detekcia alterovan\u00fdch glyk\u00e1nov asociovan\u00fdch s n\u00e1dorom vr\u00e1tane s2,3-PSA zvy\u0161uje presnos\u0165 odhalenia v\u010dasn\u00fdch \u0161t\u00e1di\u00ed PCa a redukuje tak riziko nev\u00fd\u0165a\u017enosti biopsie prostaty(5).<\/p>\n

Gratac\u00f3s-Mulleras a kol. vo svojej \u0161t\u00fadii identifikovali v\u00fdznamn\u00e9 sialyzovan\u00e9 PSA glykoformy z krvn\u00e9ho s\u00e9ra u pacientov s pokro\u010dil\u00fdm PCa a porovn\u00e1vali ich so \u0161tandardn\u00fdm PSA zo semin\u00e1lnej plazmy od zdrav\u00fdch jedincov. V\u00fdsledky uk\u00e1zali, \u017ee krvn\u00e9 s\u00e9ra s obsahom sialyzovan\u00fdch PSA glykoforiem s obsahom GalNAc zvy\u0161kov sa vyskytovali u pacientov s invaz\u00edvnym PCa, zatia\u013e \u010do zv\u00fd\u0161en\u00e9 \u03b12,6-SAPSA glykoformy vyskytuj\u00face sa u zdrav\u00fdch jedincov boli asociovan\u00e9 s v\u00fdrazne ni\u017e\u0161\u00edm rizikom invaz\u00edvneho PCa. Preto detekcia t\u00fdchto \u0161pecifick\u00fdch alterovan\u00fdch PSA glykoforiem pri invaz\u00edvnom PCa je cestou lep\u0161ej stratifik\u00e1cie pacientov z h\u013eadiska rizikovosti ochorenia(6).<\/p>\n

Podobn\u00e1 publikovan\u00e1 pr\u00e1ca Pihikova a kol. vyvinula imunotest na b\u00e1ze lekt\u00ednov, charakterizuj\u00faci glykozyla\u010dn\u00fd status PSA zo s\u00e9ra. K\u013e\u00fa\u010dov\u00e1 bola diferenci\u00e1cia medzi -2,3- a -2,6-viazanou kyselinou sialovou. V\u00fdsledky preuk\u00e1zali v\u00fdznamn\u00fd n\u00e1rast 2,3-viazanej kyseliny sialovej na PSA rozpoznate\u013enej lekt\u00ednom MAA \u2013 Maackia amurensis leukoaglutin\u00ednom <\/em>a nev\u00fdznamn\u00fd n\u00e1rast 2,6-viazanej kyseliny sialovej na PSA detegovanej pomocou SNA lekt\u00ednu \u2013 Sambucus nigra aglutin\u00ednu<\/em>. Tieto kon\u0161tatovania s\u00fa v s\u00falade s predo\u0161l\u00fdmi publikovan\u00fdmi \u0161t\u00fadiami, kde n\u00e1rast 2,6-viazanej kyseliny sialovej na PSA vo vzork\u00e1ch pacientov s PCa v porovnan\u00ed so vzorkami zdrav\u00fdch jedincov bol sp\u00e1jan\u00fd so zv\u00fd\u0161enou mierou v\u00e4zby glyk\u00e1nov na PSA v diagnostikovan\u00fdch pr\u00edpadoch. Zv\u00fd\u0161en\u00e1 sialyz\u00e1cia PSA je pritom v\u00fdsledkom upregul\u00e1cie enz\u00fdmov 2,3- a -2,6-sialyltransfer\u00e1z u pacientov s PCa(7).<\/p>\n

Kammeijer a kol. uverejnili tzv. PSA Glycomics Assay (PGA), teda test umo\u017e\u0148uj\u00faci diferenci\u00e1ciu 2,6- a 2,3-sialyzovan\u00fdch izom\u00e9rov z mo\u010du jedincov, teda markerov asociovan\u00fdch s invaz\u00edvnym typom PCa. Imunotest na b\u00e1ze lekt\u00ednov bol pou\u017eit\u00fd celkovo v 25 vzork\u00e1ch mo\u010du pacientov so suspektn\u00fdm v\u00fdskytom PCa. Celkovo 67 N-glykopeptidov bolo identifikovan\u00fdch z PSA, pri\u010dom kon\u0161tatovali, \u017ee i\u0161lo v tomto pr\u00edpade o prv\u00fd test, ktor\u00fd umo\u017enil kvantifik\u00e1ciu jednotliv\u00fdch PSA foriem z mo\u010du. T\u00fato PGA metodiku teda pova\u017euj\u00fa za s\u013eubn\u00fd n\u00e1stroj odha\u013eovania glykomarkerov v r\u00e1mci diferenci\u00e1cie medzi invaz\u00edvnymi, respekt\u00edve indolentn\u00fdmi formami a BPH(8).<\/p>\n

Sialyz\u00e1cia je proces, ke\u010f s\u00fa zvy\u0161ky kyseliny sialovej (kyseliny N-acetylneuram\u00ednovej) nadv\u00e4zovan\u00e9 na glyk\u00e1ny ako koncov\u00fd monosacharid. Zd\u00e1 sa, \u017ee pr\u00e1ve nadmern\u00e1 sialyz\u00e1cia je asociovan\u00e1 so zlou progn\u00f3zou choroby a s metast\u00e1zovan\u00edm. Realizovan\u00e9 experiment\u00e1lne anal\u00fdzy ukazuj\u00fa, \u017ee zv\u00fd\u0161en\u00e9 hladiny kyseliny sialovej s\u00fa zaznamen\u00e1van\u00e9 na s\u00e9rov\u00fdch glykoprote\u00ednoch u pacientov s n\u00e1dorom prostaty na rozdiel od ben\u00edgnej prostatickej hyperpl\u00e1zie (BPH). M\u00f4\u017eu tak predikova\u0165 Gleasonovo sk\u00f3re s vy\u0161\u0161ou senzitivitou a \u0161pecificitou ako PSA. Z\u00e1rove\u0148 vy\u0161\u0161ie s\u00e9rov\u00e9 hladiny kyseliny sialovej s\u00fa spojen\u00e9 s vy\u0161\u0161\u00edm gradingom n\u00e1doru, m\u00f4\u017eu s\u00fa\u010dasne predikova\u0165 v\u00fdskyt kostn\u00fdch metast\u00e1z(1).<\/p>\n

Ferrer-Batall\u00e9 a kol. porovn\u00e1vali PHI s vyvinutou metodikou pre glykoformy PSA zalo\u017eenou na stanoven\u00ed percentu\u00e1lneho zast\u00fapenia s\u00e9rovej 2,3-sialovej kyseliny v s\u00e9re (%2,3-SA) v skupine 79 pacientov. Kohorta zah\u0155\u0148ala 50 pacientov s PCa a 29 pacientov s BPH. Publikovan\u00e9 v\u00fdsledky uk\u00e1zali, \u017ee 2,3-SA m\u00f4\u017ee odl\u00ed\u0161i\u0165 pacientov s vysokorizikov\u00fdm karcin\u00f3mom prostaty od zvy\u0161ku pacientov lep\u0161ie ako PHI, hoci PHI lep\u0161ie koreluje s Gleasonov\u00fdm sk\u00f3re oproti % 2,3-SA. Kombin\u00e1cia oboch determinantov v\u0161ak v\u00fdznamne zvy\u0161uje senzitivitu a \u0161pecificitu diferenci\u00e1cie high-risk pacientov od low a intermediate-risk pacientov \u010di pacientov s ben\u00edgnou hyperpl\u00e1ziou prostaty. Z uveden\u00e9ho vypl\u00fdva, \u017ee oba s\u00e9rov\u00e9 mar- kery s\u00fa navz\u00e1jom komplement\u00e1rne a zvy\u0161uj\u00fa presnos\u0165 diagnostiky v pr\u00edpade identifik\u00e1cie high-rish PCa(9).<\/p>\n

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Fukozyl\u00e1cia jadra<\/h3>\n

Llop a kol. prezentovali dve metodiky na anal\u00fdzu fukozyl\u00e1cie jadra a kyseliny sialovej viazan\u00fdch PSA N-lyk\u00e1nov v s\u00e9rach 29 pacientov s BPH a 44 pacientov s PCa s r\u00f4znym \u0161t\u00e1diom ochorenia. Zaznamenali v\u00fdznamn\u00fd n\u00e1rast jadrovej fuk\u00f3zy a n\u00e1rast percenta \u03b12,3-sialyzovan\u00e9ho PSA pri high-risk PCa na rozdiel od BPH a low-risk PCa, resp. high-risk PCa pacientov. Pri cut-off hodnote pomeru PSA k jadrovej fuk\u00f3ze 0,86, m\u00f4\u017eu odl\u00ed\u0161i\u0165 high-risk PCa pacientov od BPH s vy\u0161e 90 % senzitivitou a 95 % \u0161pecificitou. V pr\u00edpade \u03b12,3-sialyzovanej PSA, pri cut-off hodnote na \u00farovni 30 % odli\u0161oval test medzi high-risk PCa a skupinou pacientov s BPH, low- a intermediate-risk PCa so senzitivitou 85,7 % a \u0161pecificitou 95,5 %. T\u00fato metodiku teda mo\u017eno do bud\u00facnosti pou\u017ei\u0165 na diferenci\u00e1ciu medzi invaz\u00edvnymi a neinvaz\u00edvnymi formami PCa(11). Uveden\u00e9 poznatky kon\u0161tatuje aj Munkley a kol., \u017ee zv\u00fd\u0161en\u00e1 fukozyl\u00e1cia jadra je zaznamen\u00e1van\u00e1 v s\u00e9rach pacientov s PCa na rozdiel od zdravej kontroly(12).<\/p>\n

Fujita \u00a0a \u00a0kol. \u00a0sk\u00famali, \u00a0\u010di \u00a0fukozylovan\u00e1 \u00a0PSA \u00a0(Fuc-PSA) v mo\u010di m\u00f4\u017ee by\u0165 pou\u017eit\u00e1 pri detekcii PCa s vysok\u00fdm Gleasonov\u00fdm sk\u00f3re. Vzorky mo\u010du zbierali u pacientov abnorm\u00e1lnym digit\u00e1lnym rekt\u00e1lnym vy\u0161etren\u00edm alebo u pacientov so zv\u00fd\u0161enou hladinou s\u00e9rov\u00e9ho PSA. ELISA s lekt\u00ednovou protil\u00e1tkou bola pou\u017eit\u00e1 na identifik\u00e1ciu Lewis-typu alebo core-typu fukozylovanej PSA (PSA-AAL) a core-typu fukozylovanej PSA (PSA-PhoSL) vo vzork\u00e1ch mo\u010du. Hladiny oboch typov Fuc-PSA boli v\u00fdznamne zn\u00ed\u017een\u00e9 u pacientov s PCa oproti t\u00fdm, u ktor\u00fdch biopsia nakoniec preuk\u00e1zala negativitu PCa. Oba typy Fuc-PSA boli v\u00fdrazne asociovan\u00e9 s vysok\u00fdm Gleasonov\u00fdm sk\u00f3re v bioptovan\u00fdch vzork\u00e1ch. Teda PSA-AAL a PSA-PhoSL boli identifikovan\u00e9 ako nez\u00e1visl\u00e9 prediktory pokro\u010dil\u00fdch PCa(13).<\/p>\n

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\u0160t\u00fadiom fukozylovanej PSA v s\u00e9re pacientov s invaz\u00edvnym PCa sa zaoberal aj Wang a kol. Pou\u017eit\u00edm PSA imunotestu na b\u00e1ze lekt\u00ednov Lens culinaris agglutinin <\/em>(LCA) a Aleuria auran<\/em>tia lectin <\/em>(AAL) boli zaznamen\u00e1van\u00e9 hladiny fukozylovan\u00fdch glykoforiem vo vzork\u00e1ch s\u00e9ra pacientov s PCa a r\u00f4znym Gleasonov\u00fdm sk\u00f3re. V\u00fdsledky meran\u00ed uk\u00e1zali, \u017ee LCA aj AAL testy zaznamenali zv\u00fd\u0161ene hladiny fukozylovanej PSA, ale iba v pr\u00edpade AAL metodiky v\u00fdsledky korelovali s vy\u0161\u0161\u00edm Gleasonov\u00fdm sk\u00f3re. V\u00fdsledkom \u0161t\u00fadie bolo, \u017ee kvantitat\u00edvne imunotesty na b\u00e1ze lekt\u00ednov na stanovenie percenta fukozylovanej PSA s pou\u017eit\u00edm lekt\u00ednu AAL m\u00f4\u017eu by\u0165 efekt\u00edvnym biomarkerom na diferenci\u00e1ciu invaz\u00edvnych PCa, obzvl\u00e1\u0161\u0165 t\u00fdch s Gleasonov\u00fdm sk\u00f3re > 7, od neinvaz\u00edvnych(13).<\/p>\n

 <\/p>\n

V\u00fdznam hodnotenia zmien glyk\u00e1nov pri n\u00e1dorovej transform\u00e1cii aj v in\u00fdch org\u00e1noch<\/h3>\n

Problematike glykozyl\u00e1cie a fukozyl\u00e1cie ako zn\u00e1mej modifik\u00e1cii glykoprote\u00ednov sa venuj\u00fa mnoh\u00e9 v\u00fdskumy aj u in\u00fdch n\u00e1dorov. Ako uv\u00e1dza Jia a kol., aberantn\u00e1 aktivita a1,6-fukozyltransfer\u00e1zy pri over-expresii FUT-8 g\u00e9nu bola pozorovan\u00e1 u pacientov v I. \u0161t\u00e1diu nemalobunkov\u00e9ho karcin\u00f3mu p\u013e\u00fac (NSCLC). Pr\u00e1ve inhib\u00edcia FUT8 m\u00f4\u017ee znamena\u0165 inhib\u00edciu rastu n\u00e1doru a metast\u00e1zovania bez z\u00e1sahu do prolifer\u00e1cie norm\u00e1lneho epitelu. Existuje teda siln\u00e1 asoci\u00e1cia over-expresie FUT8 a celkov\u00e9ho pre\u017e\u00edvania u pacientov s NSCLC a z\u00e1rove\u0148 s potenci\u00e1lnym terapeutick\u00fdm cie\u013eom(14).<\/p>\n

Fukozylovan\u00fdm \u03b11-glykoprote\u00ednom ako biomarkerom pre predikciu efektu imunoterapie u pacientov s n\u00e1dorom p\u013e\u00fac sa zaoberala pr\u00e1ca Yokobori a kol. Zaznamenali v\u00fdrazn\u00fa zmenu v glyk\u00e1novej \u0161trukt\u00fare s\u00e9rov\u00e9ho \u03b11-glykoprote\u00ednu (AGP) a zv\u00fd\u0161en\u00e9 hladiny \u03b11,3-fukozylovan\u00e9ho AGP (fAGP), ktor\u00e9 boli u pacientov asociovan\u00e9 s progresiou ochorenia a so zn\u00ed\u017eenou odpove\u010fou na chemoterapiu. Boli analyzovan\u00e9 hladiny fAGP v s\u00e9re u 39 pacientov s pokro\u010dil\u00fdm n\u00e1dorom p\u013e\u00fac s imunoterapiou nivolumabom. Celkovo 23 pacientov malo zv\u00fd\u0161en\u00fa hladinu jeden mesiac po za\u010dat\u00ed lie\u010dby a u 20 pacientov v skupine, kde nedo\u0161lo k zmen\u0161eniu n\u00e1doru, boli zaznamenan\u00e9 vysok\u00e9 hladiny fAGP s n\u00e1sledn\u00fdm \u00famrt\u00edm v tejto skupine. \u0160estn\u00e1s\u0165 pacientov, u ktor\u00fdch do\u0161lo k zn\u00ed\u017eeniu hladiny fAGP alebo k jej stagn\u00e1cii, pre\u017e\u00edvalo v \u010fal\u0161om 2-ro\u010dnom sledovanom obdob\u00ed. Z uveden\u00e9ho vypl\u00fdva, \u017ee hladina fAGP mo\u017ee by\u0165 pova\u017eovan\u00e1 za zauj\u00edmav\u00fd marker pre odhad klinickej efektivity imunoterapie nivolumabu(15).<\/p>\n

\u0160t\u00fadia publikovan\u00e1 Doherty a kol. sa sna\u017eila objasni\u0165 N-glykozyl\u00e1ciu plazmy medzi pacientmi s kolorekt\u00e1lnym karcin\u00f3mom (CRC) a so zdravou kontrolnou skupinou. Zahrnuli 633 pr\u00edpadov CRC (rozdelen\u00fdch do 4 \u0161t\u00e1di\u00ed) a 478 zdrav\u00fdch kontrol. \u0160tatisticky signifikantn\u00fd rozdiel v N-glyk\u00f3me plazmy pozorovali v r\u00e1mci v\u0161etk\u00fdch \u0161tyroch \u0161t\u00e1di\u00ed CRC, pri\u010dom v prvom \u0161t\u00e1diu bol na rozdiel od \u0161t\u00e1di\u00ed 2 a\u017e 4 zaznamenan\u00fd v\u00fdrazn\u00fd pokles fukozylovan\u00fdch glyk\u00e1nov F(6)A2G2 a F(6)A2G2S(6)1. V\u00fdsledkom je teda kon\u0161tatovanie, \u017ee N-glyk\u00f3mov\u00e9 biomarkery m\u00f4\u017eu by\u0165 s\u00fa\u010das\u0165ou klinick\u00e9ho hodnotenia \u0161t\u00e1dia ochorenia a z\u00e1rove\u0148 potenci\u00e1lnym terapeutick\u00fdm cie\u013eom(16).<\/p>\n

Pilotn\u00e1 \u0161t\u00fadia de Freitas Junior a kol. potvrdila, \u017ee \u03b12,3-sialyzovan\u00e9 povrchov\u00e9 glykolipidy, O-glyk\u00e1ny a N-glyk\u00e1ny boli exprimovan\u00e9 najm\u00e4 na histopatologick\u00fdch vzork\u00e1ch asociovan\u00fdch s mal\u00edgnou transform\u00e1ciou CRC, obzvl\u00e1\u0161\u0165 pri podtypoch s tendenciou k metast\u00e1zovaniu do region\u00e1lnych lymfatick\u00fdch uzl\u00edn. Preto anal\u00fdza glyk\u00e1nov m\u00e1 svoje postavenie pri strat\u00e9gii detekcie CRC s v\u00fdrazn\u00fdm metastatick\u00fdm potenci\u00e1lom(17).<\/p>\n

Zmenami N-glykozyl\u00e1cie asociovan\u00fdmi s CRC malignitami sa zaoberala aj Sethi a kol. \u0161t\u00fadiou na bunkov\u00fdch l\u00edni\u00e1ch CRC (LIM1215, LIM1899, and LIM2405). Detegovali v\u00fdrazn\u00fa pr\u00edtomnos\u0165 man\u00f3zov\u00fdch a \u03b12,6-sialyzovan\u00fdch N-glyk\u00e1nov, pri\u010dom \u03b21,4-GlcNAcyl\u00e1cia a \u03b12,3-sialyz\u00e1cia boli identifikovan\u00e9 v r\u00e1mci metastatickej (LIM1215) a invaz\u00edvnej (LIM2405) CRC bunkovej l\u00ednie. Z\u00e1rove\u0148 sa uk\u00e1zala siln\u00e1 asoci\u00e1cia s expresiou receptora epiderm\u00e1lneho rastov\u00e9ho faktora (EGFR)(18).<\/p>\n

 <\/p>\n

Z\u00e1ver<\/h3>\n

V\u00fdznam hodnotenia glykokonjug\u00e1tov ako potenci\u00e1lnych biomarkerov pri n\u00e1dorovej transform\u00e1cii v tkanive prostaty neust\u00e1le narast\u00e1. D\u00f4kazom je viacero publikovan\u00fdch<\/p>\n

postupov a laborat\u00f3rnych met\u00f3d zalo\u017een\u00fdch na b\u00e1ze lekt\u00ednov, ktor\u00e9 nazna\u010dili svoj praktick\u00fd potenci\u00e1lny v\u00fdznam pre klinick\u00fa prax. Pr\u00e1ve ich detekcia v mo\u010di, resp. krvnom s\u00e9re m\u00f4\u017ee prinies\u0165 nov\u00e9 menej invaz\u00edvne diagnostick\u00e9 postupy. Prim\u00e1rnym cie\u013eom je identifik\u00e1cia a odl\u00ed\u0161enie vysokomal\u00edgnych agres\u00edvnych foriem n\u00e1dorov prostaty od t\u00fdch indolentn\u00fdch. O\u010dak\u00e1va sa \u010fal\u0161ie spres\u0148ovanie metod\u00edk na b\u00e1ze lekt\u00ednov a ich zaradenie do \u0161tandardn\u00e9ho diagnostick\u00e9ho algoritmu prinesie nov\u00e9 poznatky s v\u00fdznamom nielen pre diagnostiku a pos\u00fadenie progn\u00f3zy n\u00e1dorov prostaty, ale identifikuje aj nov\u00e9 terapeutick\u00e9 ciele.<\/p>\n

 <\/p>\n

Po\u010fakovanie<\/em><\/strong><\/p>\n

Preh\u013eadov\u00fd \u010dl\u00e1nok vznikol s podporou projektu <\/em>VEGA 1\/0684\/21.<\/em><\/p>\n

 <\/p>\n

    \n
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    2. Llop E, Ferrer-Batall\u00e9 M, Barrab\u00e9s S, et al. Improvement of Prostate CancerDiagnosis by Detecting PSA Glycosylation-SpecificChanges. Theranostics<\/em>. 2016;6(8):1190-1204. doi:10.7150\/thno.15226<\/li>\n
    3. Hatakeyama S, \u00a0Yoneyama \u00a0T, \u00a0Tobisawa \u00a0Y, \u00a0Ohyama \u00a0C. \u00a0Recentprogress and perspectives on prostate Int J ClinOncol<\/em>. 2017;22(2):214-221. doi:10.1007\/s10147-016-1049-y<\/li>\n
    4. Gratac\u00f3s-Mulleras A, Duran A, AsadiShehni A, et al. Characterisation of themain PSA glycoforms in aggressive prostate cancer. SciRep<\/em>. 2020;10. doi:10.1038\/s41598-020-75526-3<\/li>\n
    5. Pihikova D, Kasak P, Kubanikova P, et Aberrantsialylation of a prostate-specificantigen: Electrochemicallabel-freeglycoprofiling in prostate cancerserumsamples. AnalChimActa<\/em>. 2016;934:72-79. doi:10.1016\/j. aca.2016.06.043<\/li>\n
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    7. Ferrer-Batall\u00e9 M, Llop E, Ram\u00edrez M, et al. Comparative Study of Blood-BasedBiomarkers, \u03b12,3-Sialic \u00a0Acid \u00a0PSA \u00a0and \u00a0PHI, \u00a0forHigh-Risk Prostate CancerDetection. Int J Mol Sci<\/em>. 2017;18(4). doi:10.3390\/ ijms18040845<\/li>\n<\/ol>\n
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      9. Sethi MK, \u00a0Hancock \u00a0WS, \u00a0Fanayan \u00a0S. \u00a0Identifying \u00a0N-Glycan \u00a0Biomarkers in Colorectal Cancer by Mass Spectrometry. AccChemRes<\/em>. 2016;49(10):2099-2106. doi:10.1021\/acs.accounts.6b00193<\/li>\n<\/ol>\n

         <\/p>\n","protected":false},"excerpt":{"rendered":"

        *A rare case of autochthonous human dirofilariasis with the manifestation of pseudotumor of the epididymis caused by helminth Dirofilaria repens   \u00davod N\u00e1dory prostaty (PCa) predstavuj\u00fa v\u00fdznamn\u00fa skupinu onkologick\u00fdch ochoren\u00ed u mu\u017eov, pri\u010dom ich incidencia a mortalita v popul\u00e1cii neust\u00e1le narast\u00e1 vzh\u013eadom na predl\u017euj\u00facu sa stredn\u00fa d\u013a\u017eku \u017eivota. Uveden\u00fd trend potvrdzuj\u00fa aj \u00fadaje z Global<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[297],"tags":[1755,1759,1292,1760,1761,1277],"class_list":["post-2267","post","type-post","status-publish","format-standard","hentry","category-pathology","tag-biomarker-en","tag-glycosylation","tag-prognosis","tag-prostate-cancer","tag-prostate-specific-antigen","tag-sialic-acid","typ_clanku-review-article"],"acf":{"abstrakt":"

        This review article aims to evaluate glycans\u2018 current position and potential as diagnostic and prognostic markers in prostate tumours. We also compare the role of the glycans as biomarkers in lung and colorectal carcinoma, where the levels of selected glycoproteins are shown to be considered the therapeutic markers. Currently used prostate tumour markers do not show sufficient specificity and sensitivity to determine the diagnosis, mainly concerning the differential diagnosis of benign and malignant disease. The diagnostic biopsy is often the only opportunity to reliably distinguish the dignity of changes. For this reason, represents the research of glycoconjugates in the tumour transformation potentially new hope to simplify the diagnostic process using less invasive and by patients better tolerated diagnostic method. Current research is focused mainly on distinguishing tumours with indolent behaviour from aggressive invasive tumours. Glycoproteins can change our view of diagnosis, but also therapy of prostate cancer in the future.<\/p>\n

        Keywords:<\/strong> Glycosylation, Prostate Cancer, Prostate-Specific Antigen, Sialic Acid, Biomarker, Prognosis<\/p>\n","casopis":[{"ID":2233,"post_author":"7","post_date":"2021-09-19 22:32:27","post_date_gmt":"2021-09-19 20:32:27","post_content":"We\u2019re bringing you this year\u2019s 1st<\/sup> issue of newslab, the scientific journal<\/strong>\r\n\r\n \r\n

          \r\n \t
        • Genomic variability of virus Sars-CoV-2<\/li>\r\n \t
        • Contribution of immunohistochemistry to histomorphological diagnostics of COVID-19 pneumonia<\/li>\r\n \t
        • Detection of microsatellite instability in Lynch syndrome-associated tumours<\/li>\r\n \t
        • Comparison of platelet glycoprotein analysis in the wholeh blood and plasma rich in platelets<\/li>\r\n \t
        • Tspan1 expression in prostatic adenocarcinoma<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-8","to_ping":"","pinged":"","post_modified":"2021-09-19 22:36:56","post_modified_gmt":"2021-09-19 20:36:56","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.newslab.sk\/casopis\/newslab-8\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"23 - 26","upload_clanok":{"ID":2265,"id":2265,"title":"NEWSLAB 1-2021_Kocan","filename":"NEWSLAB-1-2021_Kocan.pdf","filesize":467044,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2021\/09\/NEWSLAB-1-2021_Kocan.pdf","link":"https:\/\/www.newslab.sk\/en\/glycans-as-potential-markers-in-malignant-prostate-transformation\/newslab-1-2021_kocan-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab-1-2021_kocan-2","status":"inherit","uploaded_to":2267,"date":"2021-09-20 06:52:13","modified":"2021-09-20 06:52:13","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2267","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=2267"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/2267\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=2267"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=2267"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=2267"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}