Nnwale methylation DNA jikọtara ya na ekwentị maka nyocha mmalite nke etuto ahụ na nyocha leukemia na izi ezi nke 90.0%!

Nchọpụta mmalite nke ọrịa kansa dabere na biopsy mmiri mmiri bụ ntụzịaka ọhụrụ nke nchọpụta ọrịa kansa na nchoputa nke ụlọ ọrụ US National Cancer Institute tụpụtara n'afọ ndị na-adịbeghị anya, n'ebumnobi nke ịchọpụta ọrịa kansa n'oge ma ọ bụ ọbụna ọnya na-ebute ụzọ. A na-eji ya eme ihe n'ọtụtụ ebe dị ka biomarker ọhụrụ maka nchọpụta mmalite nke ọrịa ọjọọ dị iche iche, gụnyere ọrịa cancer akpa ume, etuto eriri afọ, gliomas na etuto gynecological.

Mpụta nke ikpo okwu iji chọpụta methylation landscape (Methylscape) biomarkers nwere ike imeziwanye nyocha mbụ maka ọrịa kansa, na-etinye ndị ọrịa n'oge izizi ọgwụgwọ.

N'oge na-adịbeghị anya, ndị nchọpụta ewepụtala usoro nghọta dị mfe na nke ziri ezi maka nchọpụta odida obodo methylation dabere na cysteamine mma ọla edo nanoparticles (Cyst/AuNPs) jikọtara ya na biosensor dabere na smartphone nke na-enyere aka nyocha ngwa ngwa nke ọtụtụ etuto ahụ. Enwere ike ime nyocha nke mbụ maka ọrịa leukemia n'ime nkeji iri na ise ka mmịpụta DNA sitere na nlele ọbara, yana izi ezi nke 90.0%. Aha edemede bụ nchọpụta ngwa ngwa nke DNA cancer n'ime ọbara mmadụ site na iji cysteamine-capped AuNPs na igwe nwere ike ịmụta ihe.

Ọgụgụ 1. Enwere ike imezu ikpo okwu dị mfe na ngwa ngwa maka nyocha ọrịa kansa site na ngwa Cyst/AuNP na usoro abụọ dị mfe.

E gosipụtara nke a na eserese 1. Nke mbụ, a na-eji ngwọta mmiri na-agbari iberibe DNA. Agbakwunyere Cyst/AuNP na ngwọta agwakọtara. DNA nkịtị na nke na-adịghị mma nwere ụdị methylation dị iche iche, na-eme ka mpempe DNA dị iche iche nwere usoro nhazi onwe ya dị iche iche. DNA nkịtị na-agbakọta nke ọma na-emecha chịkọta Cyst/AuNP, nke na-ebute ọdịdị nke Cyst/AuNP na-acha uhie uhie, nke mere na a pụrụ iji anya gba ọtọ hụ mgbanwe na agba site na-acha uhie uhie na-acha odo odo. N'ụzọ dị iche, profaịlụ methylation pụrụ iche nke DNA cancer na-eduga n'ịmepụta nnukwu ụyọkọ nke iberibe DNA.

E ji igwefoto smartphone were were foto nke efere olulu mmiri 96. A tụrụ DNA ọrịa kansa site na ama nwere mmụta igwe nwere atụnyere usoro dabere na spectroscopy.

Nyochaa ọrịa kansa na nlele ọbara n'ezie

Iji gbatịa ike nke ikpo okwu nghọta, ndị nyocha ahụ tinyere ihe mmetụta nke gosipụtara nke ọma n'etiti DNA nkịtị na ọrịa kansa n'ụdị ọbara n'ezie. Usoro methylation na saịtị CpG na-achịkwa okwu mkpụrụ ndụ ihe nketa. N'ihe fọrọ nke nta ka ọ bụrụ ụdị ọrịa cancer niile, mgbanwe na DNA methylation ma si otú ahụ na nkwupụta nke mkpụrụ ndụ ihe nketa na-akwalite tumourigenesis ka achọpụtara na-agbanwe.

Dị ka ihe atụ maka ọrịa cancer ndị ọzọ metụtara DNA methylation, ndị nchọpụta ahụ jiri ihe nlele ọbara sitere na ndị ọrịa leukemia na njikwa ahụike iji nyochaa irè nke ala methylation n'ichepụta ọrịa cancer leukaemic. Nke a methylation odida obodo biomarker ọ bụghị nanị na-eme ka ụzọ nyocha ọrịa leukemia ngwa ngwa dị ugbu a, ma na-egosipụtakwa ike nke ịgbatị ruo n'oge nchọpụta ọtụtụ ọrịa cancer site na iji nyocha a dị mfe ma kwụ ọtọ.

A nyochara DNA sitere na nlele ọbara sitere na ndị ọrịa leukemia 31 na ndị nwere ahụike 12. dị ka e gosiri na igbe igbe dị na Figure 2a, nnabata nke ihe atụ nke ọrịa cancer (ΔA650/525) dị ala karịa nke DNA site na nlele nkịtị. nke a bụ n'ihi mmụba nke hydrophobicity nke na-eduga na nchịkọta dị ukwuu nke DNA cancer, nke gbochiri nchịkọta nke Cyst/AuNP. N'ihi ya, ndị nanoparticles ndị a gbasasịa kpam kpam na mpụta n'ígwé nke cancer aggregates, nke mere ka a dị iche iche mgbasa nke Cyst/AuNPs adsorbed na nkịtị na cancer DNA aggregates. A na-emepụta usoro ROC site n'ịgbanwe ọnụ ụzọ site na uru kacha nta nke ΔA650/525 ruo uru kacha elu.

Ọgụgụ 2.(a) Ntụle nnabata ụkpụrụ nke cyst / AuNPs ngwọta na-egosi ọnụnọ nke nkịtị (acha anụnụ anụnụ) na cancer (red) dna n'okpuru kacha ọnọdụ.

(DA650/525) nke igbe igbe; (b) Nyocha ROC na nyocha nke nyocha nyocha. (c) Matrix mgbagwoju anya maka nyocha nke ndị ọrịa nkịtị na ọrịa cancer. (d) Mmetụta, nkọwapụta, uru amụma dị mma (PPV), uru amụma na-adịghị mma (NPV) na izi ezi nke usoro emepụtara.

Dị ka egosiri na eserese 2b, mpaghara dị n'okpuru ROC curve (AUC = 0.9274) nwetara maka ihe mmetụta mepụtara gosipụtara mmetụta dị elu na nkọwapụta. Dị ka a pụrụ ịhụ site na igbe igbe ahụ, ebe kachasị ala na-anọchite anya otu DNA nkịtị adịghị ekewa nke ọma site na ebe kachasị elu na-anọchi anya otu DNA cancer; ya mere, a na-eji mgbagha mgbagha iji chọpụta ọdịiche dị n'etiti ndị nkịtị na ndị ọrịa cancer. N'inye usoro mgbanwe ndị nwere onwe ha, ọ na-atụle ihe gbasara ihe gbasara omume na-eme, dị ka ọrịa kansa ma ọ bụ otu nkịtị. Ụdị agbanwe agbanwe dabere n'etiti 0 na 1. Ya mere, nsonaazụ ya bụ ihe gbasara omume. Anyị kpebisiri ike na njirimara ọrịa kansa (P) dabere na ΔA650/525 dị ka ndị a.

ebe b=5.3533,w1=-6.965. Maka nhazi nlele, ihe gbasara nke erughị 0.5 na-egosi nlele nkịtị, ebe ihe gbasara nke 0.5 ma ọ bụ karịa na-egosi ihe nlele kansa. Ọnụọgụ 2c na-egosipụta matrix mgbagwoju anya nke sitere na ntinye aka-ahapụ ya-naanị, nke ejiri mee ka nkwụsi ike nke usoro nhazi ọkwa. Ọnụọgụ 2d na-achịkọta nyocha nyocha nke usoro ahụ, gụnyere uche, nkọwapụta, uru amụma dị mma (PPV) na uru amụma na-adịghị mma (NPV).

Biosensors dabere na ekwentị

Iji mee ka nlele nlele dịkwuo mfe na-enweghị iji spectrophotometers, ndị nyocha ahụ jiri ọgụgụ isi mmadụ (AI) kọwaa agba nke ngwọta na ịmata ọdịiche dị n'etiti ndị nkịtị na ndị ọrịa kansa. Nyere nke a, a na-eji ọhụụ kọmputa sụgharịa agba nke ngwọta Cyst/AuNPs ka ọ bụrụ DNA nkịtị (acha odo odo) ma ọ bụ DNA cancer (red) na-eji ihe oyiyi nke efere 96 nke ọma na-ese site na igwefoto ekwentị mkpanaaka. Ọgụgụ isi nwere ike ibelata ọnụ ahịa yana melite nnweta n'ịkọwa ụcha nke ngwọta nanoparticle, na-ejighi ngwa ngwa ngwa ngwa ngwa anya ọ bụla. N'ikpeazụ, a zụrụ ụdị mmụta igwe abụọ, gụnyere Random Forest (RF) na Nkwado Vector Machine (SVM) iji wuo ụdị a. ma ụdị RF na SVM ekewapụtara ihe atụ ndị ahụ nke ọma dị ka ihe dị mma na nke na-adịghị mma yana izi ezi nke 90.0%. Nke a na-egosi na iji ọgụgụ isi eme ihe na biosensing dabere na ekwentị mkpanaka ga-ekwe omume.

Ọgụgụ 3. (a) Klas ebumnuche nke ngwọta e dekọrọ n'oge nkwadebe nke ihe nlele maka nzọụkwụ inweta ihe oyiyi. (b) Ihe atụ onyonyo emere n'oge nzọụkwụ inweta ihe onyonyo a. (c) Agba ike nke cyst/AuNPs ngwọta n'ime olulu mmiri ọ bụla nke efere 96 nke ọma ewepụtara na onyonyo a (b).

N'iji Cyst/AuNPs, ndị nchọpụta emebela nke ọma usoro nghọta dị mfe maka nchọpụta odida obodo methylation na ihe mmetụta nwere ike ịmata ọdịiche dị n'etiti DNA nkịtị na DNA cancer mgbe ha na-eji ezigbo ọbara maka nyocha ọrịa leukemia. Ihe mmetụta ahụ mepụtara gosipụtara na DNA ewepụtara site na nlele ọbara n'ezie na-enwe ike ịchọpụta ngwa ngwa na ọnụ ahịa nke ọma na DNA ọrịa kansa (3nM) n'ime ndị ọrịa leukemia n'ime nkeji iri na ise, ma gosipụta izi ezi nke 95.3%. Iji mee ka nlele nlele dịkwuo mfe site n'iwepụ mkpa maka spectrophotometer, a na-eji mmụta igwe kọwaa agba nke ngwọta na ọdịiche dị n'etiti ndị nkịtị na ndị ọrịa cancer na-eji foto ekwentị mkpanaaka, na enwere ike nweta izi ezi na 90.0%.

Ntụaka: DOI: 10.1039/d2ra05725e