Kuyeza kwa DNA methylation kuphatikiza ndi mafoni a m'manja kuti ayang'ane zotupa ndi kuyezetsa magazi m'magazi molondola 90.0%!

Kuzindikira koyambirira kwa khansa potengera madzi a biopsy ndi njira yatsopano yodziwira khansa yomwe idaperekedwa ndi US National Cancer Institute m'zaka zaposachedwa, ndi cholinga chozindikira khansa yoyambirira kapena zotupa zam'mimba. Zakhala zikugwiritsidwa ntchito kwambiri ngati chizindikiro chodziwikiratu matenda osiyanasiyana owopsa, kuphatikiza khansa ya m'mapapo, zotupa zam'mimba, ma gliomas ndi zotupa zama gynecological.

Kutuluka kwa nsanja zodziwira ma biomarker a methylation landscape (Methylscape) kumatha kupititsa patsogolo kuyezetsa komwe kulipo kale kwa khansa, kuyika odwala pamlingo wochiritsika kwambiri.

Posachedwapa, ochita kafukufuku apanga njira yosavuta yodziwira malo a methylation pogwiritsa ntchito cysteamine yokongoletsedwa ndi nanoparticles ya golide (Cyst / AuNPs) yophatikizidwa ndi biosensor yochokera ku smartphone yomwe imathandizira kuwunika koyambirira kwa zotupa zambiri. Kuyezetsa koyambirira kwa khansa ya m'magazi kungatheke mkati mwa mphindi 15 pambuyo pochotsa DNA kuchokera m'magazi, ndi kulondola kwa 90.0%. Mutu wankhani ndikuzindikira mwachangu DNA ya khansa m'magazi a munthu pogwiritsa ntchito ma AuNPs okhala ndi cysteamine-capped ndi foni yamakono yophunzirira makina.

Chithunzi 1. Njira yosavuta komanso yofulumira yodziwira khansara pogwiritsa ntchito zigawo za Cyst / AuNPs zikhoza kukwaniritsidwa mwa njira ziwiri zosavuta.

Izi zikuwonetsedwa mu Chithunzi 1. Choyamba, yankho lamadzimadzi linagwiritsidwa ntchito kusungunula zidutswa za DNA. Cyst/AuNPs adawonjezeredwa ku yankho losakanikirana. DNA yodziwika bwino komanso yoyipa imakhala ndi ma methylation osiyanasiyana, zomwe zimapangitsa kuti tizidutswa ta DNA tokhala ndi njira zodzipangira tokha. DNA yachibadwa imaphatikizana momasuka ndipo pamapeto pake imaphatikiza Cyst/AuNPs, zomwe zimapangitsa kuti Cyst/AuNPs ikhale yofiira, kotero kuti kusintha kwa mtundu kuchokera kufiira kupita ku chibakuwa kumatha kuwonedwa ndi maso. Mosiyana ndi izi, mbiri yapadera ya methylation ya khansa ya DNA imatsogolera kupanga magulu akuluakulu a zidutswa za DNA.

Zithunzi za mbale 96-zitsime zidatengedwa pogwiritsa ntchito kamera ya smartphone. Cancer DNA idayesedwa ndi foni yamakono yokhala ndi kuphunzira pamakina poyerekeza ndi njira zowonera.

Kuyeza khansa mu zitsanzo zenizeni za magazi

Kuti awonjezere kugwiritsidwa ntchito kwa nsanja yozindikira, ofufuzawo adagwiritsa ntchito sensa yomwe imasiyanitsa bwino pakati pa DNA wamba ndi khansa m'miyeso yeniyeni yamagazi. methylation pamasamba a CpG epigenetically amawongolera mafotokozedwe a jini. Pafupifupi mitundu yonse ya khansa, kusintha kwa DNA methylation ndipo motero m'mawu a majini omwe amalimbikitsa tumourigenesis awonedwa kuti asintha.

Monga chitsanzo cha makhansa ena okhudzana ndi DNA methylation, ofufuzawo adagwiritsa ntchito zitsanzo za magazi kuchokera kwa odwala khansa ya m'magazi ndi kuwongolera kwathanzi kuti afufuze momwe mawonekedwe a methylation amathandizira kusiyanitsa khansa ya m'magazi. methylation landscape biomarker iyi sikuti imangopambana njira zowonera mwachangu za khansa ya m'magazi, komanso ikuwonetsa kuthekera kopitilira kuzindikira koyambirira kwa mitundu ingapo ya khansa pogwiritsa ntchito kuyesa kosavuta komanso kolunjika kumeneku.

DNA kuchokera ku zitsanzo za magazi kuchokera kwa odwala 31 a leukemia ndi anthu 12 athanzi adawunikidwa. monga momwe tawonetsera m'bokosi lachiwonetsero mu Chithunzi 2a, kuyamwa kwachibale kwa zitsanzo za khansa (ΔA650 / 525) kunali kochepa kusiyana ndi DNA kuchokera ku zitsanzo zabwinobwino. Izi zidachitika makamaka chifukwa chakuchulukira kwa hydrophobicity komwe kumabweretsa kuphatikizika kwa khansa ya DNA, yomwe idalepheretsa kuphatikizika kwa Cyst/AuNPs. Zotsatira zake, nanoparticles anali omwazika kwathunthu mu zigawo zakunja za aggregates khansa, zomwe zinachititsa kuti kubalalitsidwa osiyana Cyst/AuNPs adsorbed pa yachibadwa ndi khansa DNA aggregates. Ma curve a ROC adapangidwa posintha malire kuchokera pamtengo wotsika wa ΔA650/525 mpaka pamtengo wokwera.

Chithunzi 2. (a) Mayankho achibale a cyst/AuNPs akuwonetsa kupezeka kwa dna yachibadwa (buluu) ndi khansa (yofiira) pansi pamikhalidwe yabwino.

(DA650/525) ya ziwembu za bokosi; (b) Kusanthula kwa ROC ndikuwunika mayeso a matenda. (c) Kusokoneza matrix pakuzindikiritsa odwala abwinobwino komanso odwala khansa. (d) Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) ndi kulondola kwa njira yopangidwira.

Monga momwe tawonetsera pa Chithunzi 2b, malo omwe ali pansi pa ROC curve (AUC = 0.9274) yomwe inapezedwa pa sensa yotukuka inasonyeza kukhudzidwa kwakukulu ndi kutsimikizika. Monga momwe tingawonere kuchokera ku bokosi la bokosi, malo otsika kwambiri omwe akuimira gulu la DNA lachibadwa silimalekanitsidwa bwino ndi malo apamwamba omwe akuimira gulu la DNA la khansa; choncho, kusinthika kwazinthu kunagwiritsidwa ntchito kusiyanitsa pakati pa magulu achibadwa ndi a khansa. Poganizira zamitundu yosiyanasiyana yodziyimira pawokha, imayerekezera kuthekera kwa chochitika, monga khansa kapena gulu labwinobwino. Kusiyana kodalira kumakhala pakati pa 0 ndi 1. Chotsatira chake ndichotheka. Tinazindikira kuthekera kwa chizindikiritso cha khansa (P) kutengera ΔA650/525 motere.

kumene b=5.3533,w1=-6.965. Pazitsanzo zamagulu, mwayi wochepera 0.5 umasonyeza chitsanzo chabwino, pamene mwayi wa 0.5 kapena wapamwamba umasonyeza chitsanzo cha khansa. Chithunzi cha 2c chikuwonetsa matrix osokonezeka omwe amapangidwa kuchokera kumalo ovomerezeka a kuchoka pawokha, omwe adagwiritsidwa ntchito kutsimikizira kukhazikika kwa njira yamagulu. Chithunzi cha 2d chikufotokozera mwachidule kuwunika koyezetsa kwa njirayo, kuphatikiza kukhudzika, kutsimikizika, mtengo wabwino wolosera (PPV) ndi mtengo wolosera (NPV).

Ma biosensor opangidwa ndi Smartphone

Kuti muchepetse kuyesa kwachitsanzo popanda kugwiritsa ntchito ma spectrophotometer, ofufuzawo adagwiritsa ntchito luntha lochita kupanga (AI) kutanthauzira mtundu wa yankho ndikusiyanitsa pakati pa anthu wamba ndi khansa. Chifukwa cha izi, masomphenya apakompyuta adagwiritsidwa ntchito kumasulira mtundu wa njira ya Cyst / AuNPs mu DNA (yofiirira) kapena DNA ya khansa (yofiira) pogwiritsa ntchito zithunzi za mbale za 96 zomwe zimatengedwa kudzera mu kamera ya foni yam'manja. Luntha lochita kupanga limatha kuchepetsa ndalama ndikuwongolera kupezeka pakutanthauzira mtundu wa mayankho a nanoparticle, komanso popanda kugwiritsa ntchito zida zilizonse zamagetsi zamagetsi zamagetsi. Pomaliza, mitundu iwiri yophunzirira makina, kuphatikiza Random Forest (RF) ndi Support Vector Machine (SVM) adaphunzitsidwa kupanga zitsanzo. mitundu yonse ya RF ndi SVM idayika bwino zitsanzozo kukhala zabwino ndi zoyipa ndikulondola kwa 90.0%. Izi zikusonyeza kuti kugwiritsa ntchito luntha lochita kupanga pakufufuza pa foni yam'manja ndikotheka.

Chithunzi 3. (a) Gulu lachindunji la yankho lolembedwa panthawi yokonzekera chitsanzo cha sitepe yopezera chithunzi. (b) Chitsanzo cha chithunzi chomwe chinatengedwa panthawi yopeza zithunzi. (c) Kuchuluka kwa mtundu wa cyst / AuNPs yankho pachitsime chilichonse cha mbale ya 96-chitsime chochotsedwa pachithunzicho (b).

Pogwiritsa ntchito Cyst/AuNPs, ofufuza apanga bwino njira yosavuta yodziwira malo a methylation ndi sensa yomwe imatha kusiyanitsa DNA yachibadwa ndi DNA ya khansa pogwiritsira ntchito zitsanzo za magazi enieni poyesa khansa ya m'magazi. Sensa yomwe idapangidwa idawonetsa kuti DNA yotengedwa ku zitsanzo zenizeni zamagazi idatha kuzindikira mwachangu komanso mopanda mtengo pang'ono DNA ya khansa (3nM) mwa odwala khansa ya m'magazi mu mphindi 15, ndipo idawonetsa kulondola kwa 95.3%. Kuti muchepetse kuyesa kwachitsanzo pochotsa kufunikira kwa spectrophotometer, kuphunzira pamakina kunagwiritsidwa ntchito kutanthauzira mtundu wa yankho ndikusiyanitsa anthu wamba ndi khansa pogwiritsa ntchito chithunzi cha foni yam'manja, ndipo kulondola kunathanso kukwaniritsidwa pa 90.0%.

Chidziwitso: DOI: 10.1039/d2ra05725e