He whakamātautau methylation DNA i honoa ki ngā waea atamai mō te tirotiro wawe i ngā pukupuku me te tirotiro leukemia me te tika o te 90.0%!

Ko te kitenga wawe i te mate pukupuku i runga i te koiora wai he huarahi hou mō te kimi me te tautuhi mate pukupuku i whakatakotoria e te US National Cancer Institute i ngā tau tata nei, me te whāinga ki te kite i te mate pukupuku wawe, tae atu ki ngā whara o mua i te mate pukupuku. Kua whakamahia whānuitia hei tohu koiora hou mō te tautuhi wawe i ngā momo mate pukupuku, tae atu ki te mate pukupuku pūkahukahu, ngā pukupuku gastrointestinal, ngā glioma me ngā pukupuku gynaecological.

Ko te putanga mai o ngā tūāpapa hei tautuhi i ngā tohu koiora o te whenua methylation (Methylscape) ka taea te whakapai ake i te tirotiro wawe mō te mate pukupuku, kia taea ai e ngā tūroro te tae ki te wāhanga wawe ka taea te rongoā.

Nō nā tata nei, kua whakawhanakehia e ngā kairangahau tētahi tūāpapa māmā, tika hoki mō te kimi i te whenua methylation i runga i ngā matūriki koura whakapaipai cysteamine (Cyst/AuNPs) me tētahi pūoko koiora e ahu mai ana i te waea atamai e āhei ai te tirotiro wawe tere i te whānuitanga o ngā pukupuku. Ka taea te tirotiro wawe mō te leukemia i roto i te 15 meneti i muri i te tangohanga DNA mai i tētahi tauira toto, me te tika o te 90.0%. Ko te taitara o te tuhinga ko te Kimi tere i te DNA mate pukupuku i roto i te toto tangata mā te whakamahi i ngā AuNP kua taupokina e te cysteamine me tētahi waea atamai e āhei ana ki te ako mīhini.

Pikitia 1. Ka taea te whakatutuki i tētahi tūāpapa māmā, tere hoki mō te tirotiro matepukupuku mā roto i ngā wāhanga Cyst/AuNPs i roto i ngā taahiraa māmā e rua.

E whakaaturia ana tēnei i te Pikitia 1. Tuatahi, i whakamahia he wairewa hei whakarewa i ngā kongakonga DNA. Kātahi ka tāpirihia ngā Cyst/AuNP ki te wairewa whakauru. He rerekē ngā āhuatanga methylation o te DNA noa me te DNA kino, ka hua ake he kongakonga DNA me ngā tauira whakakotahi-ake rerekē. Ka whakakotahi noa te DNA noa, ā, ka mutu ka whakakotahi i ngā Cyst/AuNP, ka hua ake te āhua whero-nekehanga o ngā Cyst/AuNP, kia kitea ai te huringa tae mai i te whero ki te papura ki te kanohi tahanga. He rerekē, ko te āhua methylation ahurei o te DNA matepukupuku ka hua ake he tautau nui ake o ngā kongakonga DNA.

I tangohia ngā whakaahua o ngā pereti 96-puna mā te whakamahi i tētahi kāmera waea atamai. I inehia te DNA matepukupuku mā te whakamahi i tētahi waea atamai kua whakauruhia ki te ako mīhini, ki te whakataurite ki ngā tikanga e hangai ana ki te tirotiro ira.

Te tirotiro i te mate pukupuku i roto i ngā tauira toto tūturu

Hei whakawhānui ake i te whai huatanga o te tūāpapa ine, i whakamahia e ngā kairangahau tētahi pūoko i angitu te wehewehe i waenga i te DNA noa me te DNA matepukupuku i roto i ngā tauira toto tūturu. Ko ngā tauira methylation i ngā pae CpG epigenetic e whakahaere ana i te whakaaturanga ira. I roto i te nuinga o ngā momo matepukupuku, kua kitea he rerekē ngā huringa o te methylation DNA, ā, nō reira, i roto i te whakaaturanga o ngā ira e whakatairanga ana i te tumourigenesis.

Hei tauira mō ētahi atu mate pukupuku e pā ana ki te methylation DNA, i whakamahia e ngā kairangahau ngā tauira toto mai i ngā tūroro leukemia me ngā mana hauora hei tirotiro i te whai huatanga o te whenua methylation ki te wehewehe i ngā mate pukupuku leukemia. Ehara i te mea ka pai ake tēnei tohu whenua methylation i ngā tikanga tirotiro leukemia tere o nāianei, engari e whakaatu ana hoki i te whaihua o te whakawhānui atu ki te kitenga wawe o te whānuitanga o ngā mate pukupuku mā te whakamahi i tēnei whakamātautau māmā me te tika.

I tātarihia te DNA mai i ngā tauira toto o te 31 tūroro mate pukupuku toto me te 12 tāngata hauora. E ai ki te kauwhata pouaka i te Pikitia 2a, he iti iho te mimiti whanaunga o ngā tauira mate pukupuku (ΔA650/525) i tērā o te DNA mai i ngā tauira noa. Ko te take nui o tēnei ko te pikinga o te wai e arahi ana ki te kohikohinga matotoru o te DNA mate pukupuku, i aukati i te kohikohinga o ngā Cyst/AuNP. Nō reira, i marara katoa ēnei matūriki nano ki roto i ngā paparanga o waho o ngā kohikohinga mate pukupuku, ā, i hua ake ai he marara rerekē o ngā Cyst/AuNP i piri ki ngā kohikohinga DNA noa me ngā kohikohinga DNA mate pukupuku. Kātahi ka hangaia ngā kōpiko ROC mā te whakarerekē i te paepae mai i te uara iti rawa o te ΔA650/525 ki te uara mōrahi.

Pikitia 2.(a) Ngā uara mimiti whanaunga o ngā otinga cyst/AuNP e whakaatu ana i te aroaro o te DNA noa (kikorangi) me te DNA matepukupuku (whero) i raro i ngā āhuatanga kua arotauhia

(DA650/525) o ngā kauwhata pouaka; (b) Te tātaritanga ROC me te aromatawai i ngā whakamātautau tātaritanga. (c) Te matihiko whakapoauau mō te tātaritanga o ngā tūroro noa me ngā tūroro matepukupuku. (d) Te aro, te motuhaketanga, te uara matapae pai (PPV), te uara matapae kino (NPV) me te tika o te tikanga kua whakawhanakehia.

E ai ki te Pikitia 2b, ko te horahanga i raro i te pihi ROC (AUC = 0.9274) i whiwhihia mō te pūoko kua whakawhanakehia i whakaatu i te tino aro me te motuhake. E kitea ana i te kauwhata pouaka, ko te pūwāhi iti rawa e tohu ana i te rōpū DNA noa kāore i te tino wehea mai i te pūwāhi teitei rawa e tohu ana i te rōpū DNA matepukupuku; nō reira, i whakamahia te whakatauranga logistic hei wehewehe i waenga i ngā rōpū noa me ngā rōpū matepukupuku. I runga i te huinga o ngā taurangi motuhake, ka whakatauhia te tūponotanga o te puta o tētahi huihuinga, pērā i te matepukupuku, i te rōpū noa rānei. Ko te taurangi whakawhirinaki kei waenga i te 0 me te 1. Nō reira, ko te hua he tūponotanga. I whakatauhia e mātou te tūponotanga o te tautuhi matepukupuku (P) i runga i te ΔA650/525 penei.

ko b=5.3533,w1=-6.965. Mō te whakarōpūtanga tauira, ko te tūponotanga iti iho i te 0.5 e tohu ana i te tauira noa, ko te tūponotanga 0.5, neke atu rānei, e tohu ana i te tauira matepukupuku. E whakaatu ana te Pikitia 2c i te matihiko whakapoauau i hangaia mai i te whakamana whakawhiti waiho-ā-koe, i whakamahia hei whakamana i te pumau o te tikanga whakarōpū. E whakarāpopoto ana te Pikitia 2d i te aromatawai whakamātautau tātaritanga o te tikanga, tae atu ki te aro, te motuhake, te uara matapae pai (PPV) me te uara matapae kino (NPV).

Ngā pūoko koiora e hangai ana ki te waea atamai

Hei whakangāwari ake i te whakamātautau tauira me te kore e whakamahi i ngā ine irahiko, i whakamahia e ngā kairangahau te mātauranga horihori (AI) hei whakamārama i te tae o te otinga me te wehewehe i waenga i ngā tāngata noa me ngā tāngata mate pukupuku. Nā tēnei, i whakamahia te tirohanga rorohiko hei whakamaori i te tae o te otinga Cyst/AuNPs ki te DNA noa (papura) ki te DNA mate pukupuku rānei (whero) mā te whakamahi i ngā whakaahua o ngā pereti 96-puna i tangohia mā te kāmera waea pūkoro. Ka taea e te mātauranga horihori te whakaiti i ngā utu me te whakapai ake i te urunga ki te whakamārama i te tae o ngā otinga nanoparticle, me te kore e whakamahi i ngā taputapu whatu waea atamai. Hei whakamutunga, e rua ngā tauira ako mīhini, tae atu ki te Random Forest (RF) me te Support Vector Machine (SVM) i whakangungua ki te hanga i ngā tauira. I whakarōpū tika ngā tauira RF me te SVM i ngā tauira hei pai me te kino me te tika o te 90.0%. E kī ana tēnei he tino taea te whakamahi i te mātauranga horihori i roto i te biosensing waea pūkoro.

Pikitia 3.(a) Te akomanga ūnga o te otinga i hopukina i te wā o te whakarite i te tauira mō te taahiraa hopu whakaahua. (b) Tauira whakaahua i tangohia i te wā o te taahiraa hopu whakaahua. (c) Te kaha o te tae o te otinga cyst/AuNPs i roto i ia poka o te pereti 96-poka i tangohia mai i te whakaahua (b).

Mā te whakamahi i ngā Cyst/AuNP, kua angitu ngā kairangahau ki te whakawhanake i tētahi tūāpapa arotau māmā mō te kimi i te āhua o te methylation me tētahi pūoko e taea ai te wehewehe i te DNA noa mai i te DNA matepukupuku ina whakamahia ngā tauira toto tūturu mō te tirotiro i te mate pukupuku toto. I whakaatuhia e te pūoko kua whakawhanakehia he kaha te DNA i tangohia mai i ngā tauira toto tūturu ki te kite tere me te utu-pai i ngā rahinga iti o te DNA matepukupuku (3nM) i roto i ngā tūroro mate pukupuku toto i roto i te 15 meneti, ā, i whakaatuhia he tika o te 95.3%. Hei whakahaere ake i te whakamātautau tauira mā te whakakore i te hiahia mō te ine ine, i whakamahia te ako mīhini hei whakamārama i te tae o te otinga me te wehewehe i waenga i ngā tāngata noa me ngā tāngata matepukupuku ma te whakamahi i tētahi whakaahua waea pūkoro, ā, i taea hoki te whakatutuki i te tika i te 90.0%.

Tohutoro: DOI: 10.1039/d2ra05725e