ʻO ka hoʻāʻo ʻana i ka methylation DNA i hui pū ʻia me nā kelepona akamai no ka nānā mua ʻana i nā ʻōpū a me ka nānā ʻana i ka leukemia me ka pololei o 90.0%!

ʻO ka ʻike mua ʻana i ke kanesa ma muli o ka biopsy wai he ala hou ia o ka ʻike ʻana a me ka hōʻoia ʻana i ke kanesa i hāpai ʻia e ka US National Cancer Institute i nā makahiki i hala iho nei, me ka pahuhopu o ka ʻike ʻana i ke kanesa mua a i ʻole nā ​​​​​​ʻeha precancerous. Ua hoʻohana nui ʻia ia ma ke ʻano he biomarker hou no ka ʻike mua ʻana i nā ʻano maʻi ʻino like ʻole, me ke kanesa o ka māmā, nā puʻupuʻu gastrointestinal, nā gliomas a me nā puʻupuʻu gynaecological.

ʻO ka puka ʻana mai o nā kahua e ʻike ai i nā biomarkers methylation landscape (Methylscape) he hiki ke hoʻomaikaʻi nui i ka nānā mua ʻana no ka maʻi kanesa, e kau ana i nā mea maʻi i ke kahua hiki ke mālama mua ʻia.

I kēia mau lā iho nei, ua hoʻomohala nā kānaka noiʻi i kahi kahua ʻike maʻalahi a pololei no ka ʻike ʻana i ka ʻāina methylation e pili ana i nā nanoparticles gula i hoʻonani ʻia me ka cysteamine (Cyst/AuNPs) i hui pū ʻia me kahi biosensor e pili ana i ke kelepona akamai e hiki ai ke nānā koke i nā ʻano puʻupuʻu like ʻole. Hiki ke hana ʻia ka nānā mua ʻana no ka leukemia i loko o 15 mau minuke ma hope o ka unuhi ʻana o ka DNA mai kahi hāpana koko, me ka pololei o 90.0%. ʻO ka inoa o ka ʻatikala ʻo ia ka ʻike wikiwiki ʻana i ka DNA kanesa i loko o ke koko kanaka me ka hoʻohana ʻana i nā AuNP i hoʻopaʻa ʻia e ka cysteamine a me kahi kelepona akamai i hiki ke aʻo ʻia e ka mīkini.

Kiʻi 1. Hiki ke hoʻokō ʻia kahi kahua ʻike maʻalahi a wikiwiki hoʻi no ka nānā ʻana i ka maʻi ʻaʻai ma o nā ʻāpana Cyst/AuNPs ma nā ʻanuʻu ʻelua.

Ua hōʻike ʻia kēia ma ke Kiʻi 1. ʻO ka mea mua, ua hoʻohana ʻia kahi hopena wai e hoʻoheheʻe i nā ʻāpana DNA. A laila ua hoʻohui ʻia nā Cyst/AuNP i ka hopena i hui ʻia. Loaʻa i ka DNA maʻamau a me ka DNA malignant nā ʻano methylation like ʻole, e hopena ana i nā ʻāpana DNA me nā ʻano hoʻākoakoa ponoʻī like ʻole. Hoʻohuihui ka DNA maʻamau me ka palupalu a hōʻuluʻulu hope i nā Cyst/AuNP, kahi e hopena ai i ke ʻano ʻulaʻula o Cyst/AuNPs, i hiki ke ʻike ʻia kahi loli o ke kala mai ka ʻulaʻula a i ka poni me ka maka ʻōlohelohe. I ka hoʻohālikelike ʻana, ʻo ke ʻano methylation kū hoʻokahi o ka DNA kanesa e alakaʻi ai i ka hana ʻana o nā hui nui o nā ʻāpana DNA.

Ua lawe ʻia nā kiʻi o nā papa 96-well me ka hoʻohana ʻana i kahi kāmela kelepona. Ua ana ʻia ka DNA kanesa e kahi kelepona i lako me ka aʻo mīkini i hoʻohālikelike ʻia me nā ʻano hana e pili ana i ka spectroscopy.

Ka nānā ʻana i ke kanesa ma nā hāpana koko maoli

No ka hoʻonui ʻana i ka pono o ke kahua ʻike, ua hoʻopili nā mea noiʻi i kahi sensor i hoʻokaʻawale pono ma waena o ka DNA maʻamau a me ka DNA kanesa i nā hāpana koko maoli. hoʻoponopono nā ʻano methylation ma nā wahi CpG i ka epigenetically i ka hōʻike ʻana o ka gene. Ma aneane nā ʻano maʻi kanesa āpau, ua ʻike ʻia nā loli i ka methylation DNA a pēlā i ka hōʻike ʻana o nā genes e paipai ana i ka tumourigenesis e ʻokoʻa.

Ma ke ʻano he kumu hoʻohālike no nā maʻi kanesa ʻē aʻe e pili ana me ka methylation DNA, ua hoʻohana nā mea noiʻi i nā hāpana koko mai nā poʻe maʻi leukemia a me nā kaohi olakino e noiʻi i ka pono o ka ʻāina methylation i ka hoʻokaʻawale ʻana i nā maʻi kanesa leukemia. ʻAʻole wale kēia biomarker ʻāina methylation i ʻoi aku ka maikaʻi ma mua o nā ʻano hana nānā leukemia wikiwiki e kū nei, akā hōʻike pū kekahi i ka hiki ke hoʻonui i ka ʻike mua ʻana i nā ʻano maʻi kanesa like ʻole me ka hoʻohana ʻana i kēia hoʻāʻo maʻalahi a pololei.

Ua kālailai ʻia ka DNA mai nā hāpana koko mai 31 mau maʻi leukemia a me 12 mau kānaka olakino. e like me ka mea i hōʻike ʻia ma ka pahu pahu ma ke Kiʻi 2a, ʻoi aku ka haʻahaʻa o ka absorbance pili o nā hāpana maʻi kanesa (ΔA650/525) ma mua o ka DNA mai nā hāpana maʻamau. ʻo ke kumu nui o kēia ma muli o ka hydrophobicity i hoʻonui ʻia e alakaʻi ana i ka hōʻuluʻulu paʻa o ka DNA kanesa, ka mea i pale i ka hōʻuluʻulu ʻana o Cyst/AuNPs. ʻO ka hopena, ua hoʻopuehu loa ʻia kēia mau nanoparticles i loko o nā papa o waho o nā hōʻuluʻulu kanesa, kahi i hopena ai i kahi hoʻopuehu ʻokoʻa o Cyst/AuNPs i adsorbed ma nā hōʻuluʻulu DNA maʻamau a me ke kanesa. A laila ua hana ʻia nā pihi ROC ma ka hoʻololi ʻana i ka paepae mai kahi waiwai liʻiliʻi o ΔA650/525 a i kahi waiwai kiʻekiʻe.

Kiʻi 2.(a) Nā waiwai absorbance pili o nā hopena cyst/AuNPs e hōʻike ana i ke alo o ka DNA maʻamau (uliuli) a me ke kanesa (ʻulaʻula) ma lalo o nā kūlana i hoʻomaikaʻi ʻia

(DA650/525) o nā kiʻi pahu; (b) Ka loiloi ROC a me ka loiloi ʻana o nā hoʻokolohua diagnostic. (c) Matrix huikau no ka hōʻoia ʻana o nā maʻi maʻamau a me nā maʻi kanesa. (d) ʻIke, kikoʻī, waiwai wānana maikaʻi (PPV), waiwai wānana maikaʻi ʻole (NPV) a me ka pololei o ke ʻano i hoʻomohala ʻia.

E like me ka mea i hōʻike ʻia ma ke Kiʻi 2b, ʻo ka wahi ma lalo o ke kiʻikuhi ROC (AUC = 0.9274) i loaʻa no ka sensor i hoʻomohala ʻia ua hōʻike i ka ʻike kiʻekiʻe a me ke kikoʻī. E like me ka mea i ʻike ʻia mai ka pahu pahu, ʻaʻole i hoʻokaʻawale maikaʻi ʻia ke kiko haʻahaʻa e hōʻike ana i ka hui DNA maʻamau mai ke kiko kiʻekiʻe loa e hōʻike ana i ka hui DNA maʻi kanesa; no laila, ua hoʻohana ʻia ka regression logistic e hoʻokaʻawale ma waena o nā hui maʻamau a me nā hui maʻi kanesa. Hāʻawi ʻia i kahi hoʻonohonoho o nā loli kūʻokoʻa, kuhi ia i ka hiki ke hana ʻia kahi hanana, e like me ke kanesa a i ʻole ka hui maʻamau. Aia ka loli hilinaʻi ma waena o 0 a me 1. No laila, ʻo ka hopena he hiki. Ua hoʻoholo mākou i ka hiki ke ʻike ʻia ke kanesa (P) ma muli o ΔA650/525 penei.

kahi b=5.3533,w1=-6.965. No ka hoʻokaʻawale ʻana o ka laʻana, ʻo ka hiki ke emi ma mua o 0.5 e hōʻike ana i kahi laʻana maʻamau, ʻoiai ʻo ka hiki ke 0.5 a ʻoi aku paha e hōʻike ana i kahi laʻana maʻi kanesa. Hōʻike ka Kiʻi 2c i ka matrix huikau i hana ʻia mai ka hōʻoia ʻana o ke keʻa waiho wale, i hoʻohana ʻia e hōʻoia i ke kūpaʻa o ke ʻano hoʻokaʻawale. Hōʻuluʻulu ka Kiʻi 2d i ka loiloi hoʻāʻo diagnostic o ke ʻano, me ka ʻike, ka kikoʻī, ka waiwai wānana maikaʻi (PPV) a me ka waiwai wānana maikaʻi ʻole (NPV).

Nā biosensors e pili ana i ke kelepona akamai

No ka hoʻomaʻalahi hou ʻana i ka hoʻāʻo ʻana i nā laʻana me ka ʻole o ka hoʻohana ʻana i nā spectrophotometers, ua hoʻohana nā mea noiʻi i ka naʻauao hana (AI) e wehewehe i ke kala o ka hopena a hoʻokaʻawale i waena o nā kānaka maʻamau a me nā kānaka maʻi kanesa. Ma muli o kēia, ua hoʻohana ʻia ka ʻike kamepiula e unuhi i ke kala o ka hopena Cyst/AuNPs i loko o ka DNA maʻamau (poni) a i ʻole ka DNA kanesa (ʻulaʻula) me ka hoʻohana ʻana i nā kiʻi o nā papa 96-well i lawe ʻia ma o kahi kāmela kelepona paʻalima. Hiki i ka naʻauao hana ke hōʻemi i nā kumukūʻai a hoʻomaikaʻi i ka hiki ke komo i ka wehewehe ʻana i ke kala o nā hopena nanoparticle, a me ka hoʻohana ʻole ʻana i nā mea pono kelepona paʻalima. ʻO ka hope loa, ua aʻo ʻia ʻelua mau hiʻohiʻona aʻo mīkini, me Random Forest (RF) a me Support Vector Machine (SVM) e kūkulu i nā hiʻohiʻona. ua hoʻokaʻawale pololei nā hiʻohiʻona RF a me SVM i nā laʻana he maikaʻi a maikaʻi ʻole me ka pololei o 90.0%. Hōʻike kēia he hiki ke hoʻohana ʻia ka naʻauao hana i ka biosensing kelepona paʻalima.

Kiʻi 3.(a) Papa i manaʻo ʻia o ka hopena i hoʻopaʻa ʻia i ka wā o ka hoʻomākaukau ʻana o ka laʻana no ke kaʻina hana loaʻa kiʻi. (b) Kiʻi hoʻohālike i lawe ʻia i ka wā o ke kaʻina hana loaʻa kiʻi. (c) Ikaika o ke kala o ka hopena cyst/AuNPs i loko o kēlā me kēia lua o ka pā 96-lua i unuhi ʻia mai ke kiʻi (b).

Ma ka hoʻohana ʻana i nā Cyst/AuNPs, ua hoʻomohala kūleʻa nā mea noiʻi i kahi kahua ʻike maʻalahi no ka ʻike ʻana i ka ʻāina methylation a me kahi sensor hiki ke hoʻokaʻawale i ka DNA maʻamau mai ka DNA kanesa i ka wā e hoʻohana ai i nā hāpana koko maoli no ka nānā ʻana i ka leukemia. Ua hōʻike ka sensor i hoʻomohala ʻia ua hiki i ka DNA i unuhi ʻia mai nā hāpana koko maoli ke ʻike koke a me ke kumukūʻai kūpono i nā liʻiliʻi o ka DNA kanesa (3nM) i nā maʻi leukemia i 15 mau minuke, a ua hōʻike i ka pololei o 95.3%. No ka hoʻomaʻalahi hou ʻana i ka hoʻāʻo ʻana i ka hāpana ma ka hoʻopau ʻana i ka pono no ka spectrophotometer, ua hoʻohana ʻia ke aʻo mīkini e wehewehe i ke kala o ka hopena a hoʻokaʻawale ma waena o nā kānaka maʻamau a me nā kānaka kanesa me ka hoʻohana ʻana i kahi kiʻi kelepona paʻalima, a ua hiki nō hoʻi ke hoʻokō ʻia ka pololei ma 90.0%.

Kuhikuhi: DOI: 10.1039/d2ra05725e