Nūhou

HANA HANA MINI

ʻO ka outpost e kūʻē i ka maʻi kanesa: nā hōʻailona wale nō ka maʻi kanesa āpau

Chengchen Qian1, Xiaolong Zou2, Wei Li1,3, Yinshan Li4, Wenqiang Yu5

1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, Kina;2 Keʻena o ka ʻOpe ʻana, ka Halemai Hoʻohui Mua o Harbin Medical University, Harbin 150001, Kina;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, Kina;4 Halemai Kanaka o Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750002, Kina;5Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, Kina

OLELO HOOLAHA

ʻO ke kanesa ke kumu nui o ka make ma ka honua holoʻokoʻa.Hiki i ka ʻike mua ʻana i ka maʻi kanesa ke hoʻohaʻahaʻa i ka make o nā ʻano maʻi maʻi āpau;akā naʻe, nele nā biomarkers ʻike mua i ka hapa nui o nā ʻano maʻi maʻi.ʻO ka DNA methylation ka pahuhopu nui o ka hoihoi no ka mea maʻamau ka hana ʻana o ka methylation DNA ma mua o nā loli genetic ʻē aʻe.ʻOiai e noiʻi ana i nā hiʻohiʻona maʻamau o ka maʻi kanesa me ka hoʻohana ʻana i kahi alakaʻi alakaʻi hoʻonohonoho hoʻonohonoho ʻana no ka DNA methylation, ua puka mai kekahi ʻano o nā hōʻailona maʻi āpau āpau (UCOMs) i mau moho ikaika no ka ʻike mua ʻana i ka maʻi kanesa.ʻOiai ke emi nei ka waiwai lapaʻau o nā biomarkers maʻi kanesa i kēia manawa e ka haʻahaʻa haʻahaʻa a/a i ʻole ka haʻahaʻa kikoʻī, ʻo nā hiʻohiʻona kūʻokoʻa o nā UCOM e hōʻoia i nā hopena koʻikoʻi.ʻO ka hōʻoia ʻana i ka hiki ke hoʻomaʻamaʻa o nā UCOM i loko o nā maʻi maʻi ʻāʻī, cervical, endometrial, a me urothelial maʻi maʻi e kākoʻo hou i ka noi ʻana o UCOM i nā ʻano maʻi maʻi he nui a me nā hiʻohiʻona lapaʻau like ʻole.ʻO ka ʻoiaʻiʻo, ke noiʻi nei nā noi o UCOM i kēia manawa me ka loiloi hou ʻana i ka ʻike mua ʻana o ka maʻi kanesa, ka maʻi maʻi kōkua, ka maikaʻi o ka mālama ʻana, a me ka nānā hou ʻana.ʻO nā hana molekala kahi e ʻike ai nā UCOM i nā maʻi maʻi maʻi nā kumuhana koʻikoʻi e noiʻi ʻia.Pono ka hoʻohana ʻana o UCOM i nā hiʻohiʻona o ka honua maoli i ka hoʻokō a me ka hoʻomaʻemaʻe.

HUAOLELO

ʻIke ʻana i ke kanesa;ka nānā 'ana i ke kanesa;DNA methylation;epigenetics maʻi maʻi;mea hōʻailona ola maʻi kanesa

No ke aha mākou e makemake ai i nā mea hou biomarkers?

Ma hope o ka hakakā ʻana i ka maʻi kanesa no hoʻokahi haneli, ʻo ka maʻi kanesa ka mea hoʻoweliweli ola kino loa i ke kanaka.ʻO ka maʻi maʻi e hoʻomau nei i ke olakino olakino me 19.3 miliona mau hihia hou a kokoke i 10 miliona mau make i manaʻo ʻia ma 20201. I ka makahiki 2020 he 4.6 miliona mau hihia hou o ka maʻi kanesa i ʻike ʻia ma Kina, ʻo ia ka 23.7% o nā hihia maʻi maʻi hou ma ka honua e like me GLOBOCAN1.Eia kekahi, ma kahi o 3 miliona mau make i pili i ka maʻi kanesa ma Kina i 2020, ʻo ia ka 30% o nā make pili i ka maʻi maʻi honua1.Ua hōʻike ʻia kēia mau helu helu ʻo Kina ke kūlana mua ma ka helu a me ka make o ka maʻi kanesa.Eia kekahi, he 40.5% ka nui o ke ola maʻi maʻi maʻi 5 makahiki, ʻo ia ka 1.5 mau manawa haʻahaʻa ma mua o ka helu ola 5 makahiki ma United States2,3.ʻO ka haʻahaʻa haʻahaʻa haʻahaʻa o ke ola a me ka nui o ka make ma Kina ma mua o nā ʻāina me nā papa kuhikuhi hoʻomohala kanaka kiʻekiʻe e hōʻike ana e koi koke ʻia kahi ʻōnaehana pale a me ka nānā ʻana i ka maʻi kanesa.ʻO ka ʻike mua ʻana i ka maʻi kanesa kekahi o nā mea koʻikoʻi loa i loko o kahi ʻōnaehana olakino.Hiki i ka ʻike mua ʻana i ka maʻi kanesa ke hoʻomaikaʻi i ka wānana a me ke ola ʻana i ka wā mua ma kahi kokoke i nā ʻano maʻi maʻi āpau4.Ua alakaʻi ʻia nā hoʻolālā kānana kūleʻa i ka emi ʻana o ka nui o ka maʻi maʻi o ka cervical, breast, colorectal, a me ka prostate.

ʻAʻole naʻe he hana maʻalahi ka loaʻa ʻana o ka maʻi kanesa.ʻO ka noiʻi ʻana i ka biology a me ka wānana o ka maʻi maʻi maʻi mua, ʻo ka ʻike ʻana a me ka hōʻoia ʻana i nā biomarkers ʻike mua pono, a ʻo ka hoʻomohala ʻana i nā ʻenehana ʻike makamua hiki ke loaʻa a pololei hoʻi ʻo ia ka mea nui loa i ke kaʻina hana4.Hiki i ka ʻike pololei ʻana i ka maʻi kanesa ke hoʻokaʻawale i nā maʻi maʻi mai nā maʻi ʻino, e kōkua i ka pale ʻana i nā kaʻina hana pono ʻole a hoʻomaʻamaʻa i ka mālama ʻana i nā maʻi.ʻO nā hoʻolālā ʻike mua i kēia manawa e pili ana i nā biopsies endoscope-based, imaging medical, cytology, immunoassays, a me nā hōʻike biomarker5-7.Ma muli o ka hoʻopiʻi a me ke kumu kūʻai, lawe nā biopsies endoscope i ke kaumaha koʻikoʻi ma ke ʻano he hana lapaʻau nui e hilinaʻi ana i nā limahana limahana.E like me ka cytology, pili nā ʻano hana ʻelua i nā ʻoihana lapaʻau a ua hoʻokumu ʻia i ka hoʻoholo pilikino me kahi hana i mamao loa mai ka ideal8.ʻO ka ʻokoʻa, ʻaʻole pololei loa nā immunoassays, hāʻawi ʻia i nā helu kuhi hewa kiʻekiʻe.ʻO ke kiʻi lāʻau lapaʻau, ma ke ʻano he loiloi screening, pono nā lako makamae a me nā ʻenehana loea.No laila, ua kaupalena ʻia ke kiʻi olakino ma muli o ka haʻahaʻa o ka hiki.No kēia mau kumu, ʻoi aku ka maikaʻi o nā biomarkers no ka ʻike mua ʻana i ka maʻi kanesa.

Ka leka iā: Yinshan Li a me Wenqiang Yu

Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn

ORCID ID: https://orcid.org/0009-0005-3340-6802 a

https://orcid.org/0000-0001-9920-1133

Loaʻa iā ʻAukake 22, 2023;ʻae ʻia ʻOkakopa 12, 2023;

paʻi ʻia ma ka pūnaewele ʻo Nowemapa 28, 2023.

Loaʻa ma www.cancerbiomed.org

Laikini Kūikawā-NonCommercial 4.0 International

Hoʻokaʻawale ʻia nā biomarkers ma ke ʻano he protein, DNA mutation markers, epigenetic markers, chromosomal abnormalities, RNA markers i loaʻa pololei mai nā ʻōpū, a i ʻole nā ʻāpana tumo i loaʻa ʻole mai nā wai o ke kino.ʻO nā māka protein ka mea i hoʻohana nui ʻia i nā biomarkers i ka nānā ʻana a me ka maʻi kanesa.ʻO nā biomarkers protein, e like me ka screening bio-markers, ua kaupalena ʻia e ka manaʻo e hoʻopili ʻia e nā leona maikaʻi, e alakaʻi ana i ka overdiagnosis a me ka overtreatment, e like me ka mea i hōʻike ʻia no ka α-fetoprotein a me ka prostate-specific antigen (PSA) 9,10.Hoʻokomo ʻia nā hōʻailona RNA i nā hiʻohiʻona hōʻike genetic a me nā hōʻailona RNA non-coding ʻē aʻe. Hiki ke ʻike ʻia kahi hui pū ʻana o nā hōʻailona RNA hōʻailona me ka hoʻohana ʻana i nā laʻana mimi, ʻaʻole mamao loa ka naʻau (60%) no nā maʻi maʻi mua, a ʻo ka ʻike ʻana i hiki ke ʻike ʻia. e hoʻopili ʻia e ke ʻano hoʻohaʻahaʻa maʻalahi o ka RNA ma ke kaiapuni maʻamau11.Ke kū nei nā hōʻailona genetic a me epigenetic i ka pilikia o ka maʻi maʻi maʻi a me ka palena i nā ʻano maʻi kanesa.

He moho ikaika ka DNA methylation ma ke ʻano he biomarker ʻike mua ʻia mai ka wā i hoʻopili mua ʻia ai ʻo Feinberg i ka maʻi kanesa ma 198312. ʻIke ʻia nā aberrations DNA methylation ma nā pae āpau o ka maʻi kanesa, e like me ka wā mua.Hana pinepine ka Aberrant DNA hypermethylation ma nā mokupuni CpG i nā mea hoʻolaha gene e pale aku i nā suppressors tumor13,14.Ua hōʻike pū ʻia nā haʻawina e pili ana ka hypermethylation DNA kūlohelohe i ka hoʻoponopono ʻana o nā mea hoʻoponopono hoʻomohala15.ʻO ke awāwa methylation DNA, ka mea maʻamau e pili ana me nā mea hoʻomohala hoʻomohala a me nā maʻi maʻi hypermethylated, hiki ke hoʻololi i ke ʻano hōʻike gene i kahi ʻano hilinaʻi DNA methylation paʻa a hoʻemi i ka pilina i ka methylated histone H3K27me3 a me nā protein polycomb pili16,17.

Ma waena o ka nui o nā hōʻailona DNA methylation i paʻi ʻia, ua hoʻomaka maikaʻi kekahi ma ka mākeke;akā naʻe, ʻaʻole naʻe i wehe piha nā mākaʻi DNA methylation a me nā panela diagnostic i kēia manawa i ka hiki ke ʻike mua i ka maʻi kanesa no nā kumu he nui18.ʻOiai ʻo ka hapa nui o ka hōʻike ʻana i ka hana ʻae ʻia me ka hoʻohana ʻana i ka ʻikepili waihona, ʻoi aku ka maikaʻi o kēia mau biomarkers ma ka honua maoli ma muli o ka ʻoi aku o ka paʻakikī o nā laʻana o ka honua maoli a ʻaʻole like me ka poʻe i koho ʻia ma nā waihona.Ua hōʻike ʻia ka ʻike mua ʻana o ka methylation ma muli o ka hanauna hou aʻe he 16.8% a me 40.4% ka naʻau i nā maʻi maʻi maʻi maʻi I a me II.Pono nā ho'āʻo ʻike mua i ke kūpaʻa a me nā biomarkers pololei.

ʻIke ʻia ʻo Universal cancer only marker (UCOM) me ka hoʻohana ʻana i ke kaʻina hoʻonohonoho alakaʻi (GPS)

ʻOiai he mau ʻumi makahiki o ka noiʻi ʻana i ka maʻi kanesa, ʻaʻole i ʻike ʻia ka pale ʻana a me ka mālama ʻana.Pono nā ʻano hana hou e hiki ai i nā mea noiʻi ke loiloi pono i ka maʻi kanesa.I nā makahiki he 23 i hala iho nei, ua hoʻonui ʻia nā hiʻohiʻona e like me ka nonmutational epigenetic reprogramming a me ka polymorphic microbiomes20,21.I ka wehe ʻia ʻana o nā kikoʻī hou aku e pili ana i ka maʻi kanesa, ua hoʻokomo ʻia nā manaʻo hou aʻe i ka noiʻi maʻi kanesa.Ua hele mālie ka noiʻi ʻana i ka maʻi maʻi i ke ʻano hou ma nā ʻaoʻao ʻelua (commonality and individuality).Me ka hoʻomohala ʻana o ka oncology precision i nā makahiki i hala iho nei, ke hilinaʻi nei ka manaʻo o ka noiʻi maʻi maʻi i ka lāʻau lapaʻau hoʻokahi a me ka heterogeneity o ka maʻi kanesa22.No laila, ua ʻike nui ʻia nā biomarkers maʻi maʻi i kēia manawa i nā ʻano maʻi maʻi kūikawā, e like me PAX6 force-vical cancer23 a me BMP3 no ka colorectal cancer24.ʻOkoʻa ka hana o kēia mau biomarkers i nā ʻano maʻi kanesa, akā ʻaʻole hiki i nā poʻe maʻi ke hana i ka nānā ʻana no nā maʻi maʻi āpau i ka manawa like ma muli o ka palena o ka loaʻa ʻana o ka laʻana olaola a me ke kumukūʻai kiʻekiʻe.He mea maikaʻi inā hiki iā mākou ke ʻike i kahi biomarker ikaika i kūpono no nā ʻano maʻi maʻi āpau i ka wā mua.

No ka hoʻokō ʻana i kēlā pahuhopu maikaʻi, pono e koho ʻia kahi moho biomarker maikaʻi aʻe mai ka papa inoa o nā ʻano biomarker.ʻO ka DNA methylation aberrations, ma waena o nā moʻo a me ka epigenetic profiles, ua ʻike ʻia e pili ana i ka maʻi kanesa a ʻo ia kekahi o nā mea mua loa, inā ʻaʻole ʻo ka mua, hiki mai nā mea ʻino e pili ana i ka maʻi kanesa ma ka manawa.Ua hoʻomaka mua ka hoʻokolokolo ʻana o ka methylation DNA, akā ua pale ʻia e ka nele o nā ʻano noiʻi.Ma waena o 28 miliona mau pūnaewele CpG methylated i loko o ka genome, pono e ʻike ʻia kahi helu hoʻokele a hoʻopili ʻia i ka genome e hoʻomaopopo maikaʻi ai i ka tumorigenesis.ʻO ka genome bisulfite sequencing (WGBS), ka mea i manaʻo ʻia ʻo ia ke kūlana gula o ka DNA methylation sequencing, hiki ke uhi wale i 50% o Cs i loko o nā maʻi maʻi maʻi ma muli o ke ʻano o ka lāʻau bisulfite e wāwahi i nā ʻāpana DNA a hoʻohaʻahaʻa i ka paʻakikī genome i ka wā. ka hoololi ana o Cs-to-Ts25.ʻO nā ala ʻē aʻe, e like me 450k chips, uhi wale i ka 1.6% o ka genome methylation.Ma muli o ka ʻikepili he 450k, he 35.4% ka naʻau o ka DNA methylation detection panel no 6 mau ʻano maʻi maʻi maʻi maʻi maʻi 126.ʻO nā palena o nā ʻano maʻi kanesa, nā hana maikaʻi ʻole, a me ka walaʻau i hana ʻia e nā ala ʻike i ke kaʻina analytic ua lilo i mea keakea nui loa no nā pan-cancer detection panels.

No ka noiʻi maikaʻi ʻana i nā hiʻohiʻona epigenetic o nā cell i ka wā tumorigenesis a me ka metastasis, ua kūkulu mākou i kahi GPS kūʻokoʻa no ka genome-wide DNA methylation detection, e uhi ana i ka 96% o nā pūnaewele CpG ma 0.4 billion reads25.ʻO GPS kahi hana hoʻokaʻina bilateral me ka hoʻohana ʻana i ka hopena 3′ o ka ʻāpana DNA o nā methyl-cytosines hiki ʻole ke hoʻololi ʻia ma hope o ka mālama ʻana i ka bisulfite e alakaʻi ana i ka hoʻolikelike ʻana o ka helu ʻana o ka methylation DNA o ka hopena 5′ ma o ka hoʻopaʻa ʻana i nā hopena pālua (Figure 1)25.ʻO ke kaula alakaʻi methyl-cytosine, e hana ana ma ke ʻano he kumu hoʻohālike, kōkua i ka alignment ʻāina kiʻekiʻe-GC e hoʻihoʻi i ka ʻikepili sequencing haʻalele loa i ka WGBS kuʻuna.Hāʻawi ka hiʻohiʻona uhi kiʻekiʻe o GPS i ka nui o ka ʻike DNA methylation, e hiki ai iā mākou ke nānā i nā profile methylation cancer me kahi hoʻonā kiʻekiʻe loa ma nā wahi i noiʻi ʻia ma mua.

Hāʻawi ʻo GPS iā mākou i kahi mea hana ikaika e noiʻi ai i ka homogeneity o ka maʻi kanesa, hiki ke maʻalahi i ka noiʻi ʻana i ka maʻi kanesa a loaʻa paha kahi wehewehe ākea no ka tumorigenesis a me ka metastasis.ʻOiai ke kālailai ʻana i ka ʻikepili GPS o nā laina kelepona maʻi maʻi, ua ʻike pinepine ʻia kahi hanana kūʻokoʻa.Aia kekahi mau ʻāpana i ʻike ʻia he hypermethylated maʻamau i nā ʻano laʻana maʻi kanesa.Ua hōʻoia ʻia kēia ʻike i manaʻo ʻole ʻia e lawelawe ma ke ʻano he UCOM.ʻOi aku ma mua o 7,000 mau laʻana mai 17 mau ʻano o ka maʻi maʻi maʻi ma The Cancer Genome Atlas (TCGA) database ua hoʻopaʻa ʻia, ma waena o mākou i ʻike ai i ka UCOM mua, HIST1H4F, kahi moʻo pili histone i hypermethylated i nā ʻano maʻi cancer27.Ua loaʻa a hōʻoia ʻia kekahi ʻano UCOM ma ka waihona TCGA, ka Gene Expression Omnibus (GEO) database, a me nā hōʻailona lapaʻau maoli.I kēia manawa, ua loaʻa a hōʻoia ʻia ʻo HIST1H4F, PCDHGB7, a me SIX6 ma ke ʻano he UCOM.Hāʻawi ka loaʻa ʻole ʻana o nā UCOM i kahi pane ikaika i ka pono o ka ʻike mua ʻana i ka maʻi kanesa.Hāʻawi nā UCOM i kahi hopena no ka ʻike ʻana i ka māka hoʻokahi o nā maʻi maʻi he nui.

Nā hiʻohiʻona o nā UCOM

Ma ka hōʻoia ʻana, ua hōʻike ʻia nā UCOM e hōʻike i ʻehā mau hiʻohiʻona nui e hiki ai i nā UCOM ke ʻoi aku ma mua o ka pono o nā biomarkers o kēia manawa (Figure 2).

Kūʻokoʻa i ka malignancy

He kū hoʻokahi nā UCOM i nā maʻi maʻi maʻi a i ʻole ma mua o ka maʻi kanesa a ʻaʻole i hoʻopilikia ʻia e nā loli physiologic maʻamau.ʻO kekahi o nā hōʻailona pili i ka maʻi kanesa o kēia manawa i hoʻohana nui ʻia i ka ʻike mua ʻana a/a i ʻole ka nānā ʻana i alakaʻi i ka overdiagnosis.ʻIke ʻia nā pae PSA kiʻekiʻe, kahi mea hana hōʻoia hōʻoia i ke kino, i nā kūlana maikaʻi, e like me ka prostate hyperplasia a me prostatitis10.ʻO ka hoʻomaʻamaʻa nui ʻana a me ka hopena o ka mālama ʻana e alakaʻi i ka maikaʻi o ke ola ma muli o ka ʻōpū, ka mimi, a me nā pilikia pili wahine28.ʻO nā mea biomarkers i hoʻokumu ʻia i ka protein a i hoʻohana nui ʻia i loko o ke keʻena lapaʻau, e like me CA-125, ʻaʻole i hāʻawi i nā pōmaikaʻi koʻikoʻi i ka wā e loaʻa ana ka overdiagnosis a me ka overtreatment29.ʻO ke kūlana kiʻekiʻe o nā UCOM no nā maʻi maʻi e pale i kēia mau pōkole.Hoʻokaʻawale maikaʻi ka UCOM, PCDHGB7, i nā ʻeha intraepithelial squamous kiʻekiʻe (HSILs) a me ka maʻi maʻi ʻāʻī mai nā laʻana maʻamau a me nā liona squamous intraepithelial haʻahaʻa (LSILs), ʻoiai ʻo ka hapa nui o nā mea biomarkers hiki ke hoʻokaʻawale wale i ka maʻi maʻi cervical mai nā laʻana maʻamau30.ʻOiai ʻaʻole ʻike ʻo PCDHGB7 i nā ʻokoʻa nui ma waena o ka endometrium maʻamau a me ka hyperplasia endometrial, ʻike ʻia nā ʻokoʻa nui ma waena o ka endometrium maʻamau a me ka hyperplasia atypical, a ʻike ʻia nā ʻokoʻa ʻoi aku ma waena o ka endometrium maʻamau a me ka maʻi maʻi endometrial (EC) ma muli o PCDHGB731.He mea kū hoʻokahi nā UCOM i nā maʻi ʻino i loko o nā waihona a me nā hōʻailona lapaʻau.Mai ka hiʻohiʻona o ka mea maʻi, hoʻemi nā UCOM kūʻokoʻa i ka paepae no ka hoʻomaopopo ʻana i nā hōʻailona paʻakikī o nā ʻano biomarkers paʻa maikaʻi ʻole a me ka hopohopo pili i ka wā o ka loiloi.Mai ka manaʻo o ke kauka, hoʻokaʻawale nā UCOM kūʻokoʻa i nā maʻi maʻi mai nā maʻi liʻiliʻi, e kōkua ana i ka hoʻāʻo ʻana o nā maʻi a hōʻemi i nā kaʻina hana lapaʻau pono ʻole a me ka hoʻomaʻamaʻa ʻana.No laila, ho'ēmi nā UCOM kū hoʻokahi i ka hoʻemi ʻana o ka ʻōnaehana olakino, hoʻopau i ka pilikia o ka ʻōnaehana, a hoʻolako i nā kumuwaiwai olakino hou aku i ka poʻe nele.

Kiʻi 1 Schematic o GPS workflow no ka DNA methylation detection25.Laina hina: hoʻokomo i ke kaʻina DNA;laina ʻulaʻula: Hana ʻia ka DNA me ka T4 DNA polymerase, e hoʻololi ana i ka cytosine me 5′-methylcytosine ma ka hopena 3′ o ka hoʻokomo;polū C me Me: methylated cytosine;uliuli C: unmethylated cytosine;melemele T: thymine25.

ʻO nā mea a pau a i ʻole

Aia nā UCOM i loko o nā pūnana ma'i 'a'ai wale nō a 'ike pa'a 'ia ma kahi kokoke i nā keneta ma'i 'a'ai.Ua hōʻoia ʻia ʻo HIST1H4F e hypermethylated ma kahi kokoke i nā ʻano tumo āpau akā ʻaʻole i nā laʻana maʻamau27.Pēlā nō, ua hōʻike ʻia ʻo PCDHGB7 a me SIX6 i hypermethylated i nā laʻana tumo āpau akā ʻaʻole i nā samples maʻamau30-32.Hoʻomaikaʻi nui kēia ʻano ʻokoʻa i ka hana o nā UCOM e pili ana i ka palena o ka ʻike a me ka ʻike.Hiki ke hoʻokaʻawale ʻia ka 2% o nā pūnaewele maʻi maʻi i loko o nā laʻana, e hana ana i nā UCOM i biomarker koʻikoʻi loa ma mua o ka hapa nui o nā biomarkers30. Ma ke ʻano he biomarker i hoʻohana ʻia no ka ʻike ʻana i ka maʻi maʻi ʻaʻai, KRAS mutations aia wale nō ma kahi o 36% o nā hihia maʻi maʻi colorectal. manaʻo maikaʻi ʻole ka hiki ke hoʻomaʻamaʻa33.ʻO ka haʻahaʻa haʻahaʻa o ka hoʻololi ʻana o KRAS i ka maʻi maʻi colorectal ka palena o KRAS i ka hui pū ʻana me nā biomarkers ʻē aʻe.ʻO ka ʻoiaʻiʻo, ʻo ka hui pū ʻana o nā biomarkers me he mea lā he mea hoʻohiki i ka wā mua, akā ʻaʻole e hoʻopuka mau i kahi hopena ʻoluʻolu aʻo ka hōʻike ʻana i ka walaʻau nui i ka nānā ʻana a me ka maʻamau e pili ana i nā kaʻina hana hoʻokolohua paʻakikī.I ka hoʻokaʻawale ʻana, aia ka PCDHGB7 a me nā UCOM ʻē aʻe i nā maʻi maʻi āpau.ʻIke nā UCOM i nā mea maʻi maʻi maʻi i nā ʻano laʻana maʻi maʻi me ka pololei loa i ka wā e hoʻopau ana i nā kaʻina noiʻi paʻakikī no ka hoʻopau ʻana i ka walaʻau.ʻAʻole paʻakikī ka ʻike ʻana i ka maʻi maʻi i loko o kahi laʻana nui, akā paʻakikī loa ka ʻike ʻana i ka maʻi kanesa ma kahi laʻana liʻiliʻi.Hiki i nā UCOM ke ʻike i ka liʻiliʻi o ka maʻi kanesa.

Kiʻi 2 Nā ʻano o nā UCOM.

ʻIke ʻia ka maʻi maʻi ma mua o nā loli pathological

Hiki ke ʻike ʻia nā UCOM i ka pae pre-cancerous ma mua o nā loli pathological.Ma keʻano he epigenetic biomarkers, hiki i ka UCOM abnormalities ma kahi mua ma mua o ka phenotypic abnormalities a ʻike ʻia i loko o ka tumorigenesis, ka holomua, a me ka metastasis34,35.ʻO ka naʻau o ka UCOM i ka manawa e hoʻonui ai i ka hana UCOM i ka ʻike ʻana i ka maʻi maʻi ma mua o ka maʻi maʻi.ʻO ka ʻike ʻana i ka maʻi maʻi mua e pili ana i nā biopsies a me ka cytology hiki ke paʻakikī no ka poʻe pathologists ʻike loa.Ua hōʻike ʻia kahi biopsy hoʻokahi i loaʻa ma o ka colposcopy he maikaʻi ma 60.6% o nā laʻana HSIL+.Pono nā biopsies hou no nā ʻeha he nui e hoʻonui i ka naʻau36.ʻO ka ʻokoʻa, ʻo ka UCOM, PCDHGB7, he 82% no nā laʻana HSIL+, ma mua o ka naʻau o nā biopsies a me ka hapa nui o nā biomarkers30.ʻO ka methylation marker, FAM19A4, he 69% ka naʻau no CIN2+, he like ia me ka cytology, akā ʻaʻole hiki ke hoʻokaʻawale i ka CIN1 mai nā laʻana maʻamau37.Ua hōʻike ʻia nā UCOM i kahi biomarker ʻike mua loa.I ka hoʻohālikelike ʻia me nā pathologists e pili ana i ka ʻike, ʻoi aku ka maikaʻi o ka ʻike ʻana o nā UCOM no nā maʻi maʻi maʻi mua, ʻo ia hoʻi ke kōkua i ka hoʻomaikaʻi ʻana i ka wānana maʻi a me ke ola ʻana30.Hoʻohui, hāʻawi nā UCOM i kahi kahua ʻike i hiki ke loaʻa i nā wahi i nele i nā pathologists ʻike a hoʻomaikaʻi nui i ka pono ʻike.Me nā kaʻina hana hoʻohālike like ʻole a me nā kaʻina ʻike, loaʻa ka ʻike UCOM i nā hopena kūpaʻa a maʻalahi hoʻi i kūpono i kahi protocol screening e koi ana i ka liʻiliʻi o nā limahana ʻoihana a me nā kumuwaiwai olakino.

Maʻalahi e ʻike

ʻO nā ʻano hana i kēia manawa no ka ʻike ʻana i ka methylation DNA he paʻakikī a hoʻopau manawa.Pono ka hapa nui o nā ʻano hana i ka hoʻololi ʻana i ka bisulfite, kahi e hoʻopau ai i ka maikaʻi o ka laʻana a hoʻopuka paha i nā hopena paʻa ʻole a pololei ʻole.ʻO ka maikaʻi ʻole o ka hana hou ʻana ma muli o ka mālama ʻana i ka bisulfite hiki ke alakaʻi i ka huikau no nā kauka a me nā maʻi a keʻakeʻa hou aku i ka hahai ʻana a/a i nā hoʻolālā lapaʻau.No laila, ua hoʻololi hou mākou i ke ʻano o ka ʻike ʻana i ka UCOM e pale aku i ka mālama ʻana i ka bisulfite pilikia o nā laʻana, e hoʻokō i nā koi noi noiʻi, a hoʻonui i ka hiki.Ua hoʻomohala mākou i kahi ʻano hana hou me ka hoʻohana ʻana i nā enzyme restriction methylation-sensitive i hui pū ʻia me ka PCR (Me-qPCR) fluorescent manawa maoli e helu i ke kūlana methylation o UCOMs i loko o 3 mau hola me ka hoʻohana ʻana i nā kaʻina hana maʻalahi (Figure 3).Hiki i ka Me-qPCR ke hoʻokomo i nā ʻano laʻana like ʻole, e like me ka hōʻiliʻili kino o nā wai kino a me nā laʻana mimi i hōʻiliʻili ponoʻī.Hiki ke hana ʻia, mālama ʻia, a maʻalahi hoʻi i ka ʻike ʻana me ka hoʻohana ʻana i ka ʻili DNA maʻamau a maʻalahi.A laila hiki ke hoʻopili pololei ʻia ka DNA i unuhi ʻia i ka paepae Me-qPCR no ka hopena hoʻokahi-pot a me nā hopena helu hoʻopuka.Ma hope o ka nānā ʻana i ka hopena maʻalahi me ka hoʻohana ʻana i nā hiʻohiʻona diagnostic i hoʻopili ʻia a hōʻoia ʻia i nā ʻano maʻi maʻi kūikawā, ua unuhi ʻia ka hoʻoholo hope loa o nā hopena ʻike UCOM a hōʻike ʻia he waiwai semi-quantitative.ʻOi aku ka maikaʻi o ka paepae Me-qPCR i ka bisulfite-pyrosequencing kuʻuna i ka ʻike UCOM ʻoiai e mālama ana i 3 mau hola o ka hoʻololi ʻana i ka bisulfite, e like me ka protocol EZ DNA Methylation-Gold kit.ʻO ke kahua ʻike ʻike methylation hou e hoʻokūpaʻa i ka UCOM detection stable, ʻoi aku ka pololei, a ʻoi aku ka maʻalahi30.

Kiʻi 3 Kaʻina hana ʻike o nā UCOM.Loaʻa nā ʻano laʻana i ka BALF i hoʻohālikelike ʻia e ka ʻoihana, ka palaki Pap, a/a i ʻole ka mimi i hōʻiliʻili ponoʻī.Hiki ke hoʻokomo i ke kaʻina hana hoʻoheheʻe DNA i kahi extractor maʻalahi, hiki ke ʻike pololei ʻia ka huahana e qPCR.

Ka hoʻohana ʻana i nā UCOM

Ka ma'i 'a'ai

'O ka ma'i 'a'ai 'o ia ka lua o ka ma'i 'a'ai ma'amau a make loa ma ka honua holo'oko'a, he 11.4% o nā ma'i hou a me 18.0% o nā make hou1.Ma waena o nā maʻi maʻi āpau, 85% he maʻi maʻi maʻi ʻaʻai liʻiliʻi liʻiliʻi (NSCLC) a he 15% he maʻi maʻi maʻi maʻi liʻiliʻi liʻiliʻi (SCLC), ʻoi aku ka kiʻekiʻe o ka malignancy38.ʻO ka scanning computed tomography haʻahaʻa (LDCT) ke ʻano o ka nānā ʻana i kēia manawa no ka maʻi kanesa a ua hōʻike ʻia e hoʻomaikaʻi i ka ʻike mua ʻana a hoʻemi i ka make6;akā na'e, ma muli o ka ha'aha'a ha'aha'a a me ka hiki 'ole ke komo, 'a'ole i lawelawe 'o LDCT ma ke 'ano he ala ho'ona'auao 'olu'olu, e like me nā hō'ailona ma'i 'a'ai ma'amau, e like me CEA39.ʻO nā kumukūʻai a me nā mea hiki no nā maʻi i hala a me nā kuhi hewa o ka hoʻolālā screening LDCT ke keʻakeʻa nei i ka holomua o ka hoʻolaha ʻana i ka maʻi maʻi maʻi ʻaʻai40.ʻO HIST1H4F, he UCOM, he mana nui loa ma ke ʻano he biomarker ʻike mua i ka wai bronchoalveolar (BALF) samples27.HIST1H4F ua hypermethylated i loko o ka lung adenocarcinoma a me ka lung squamous cell carcinoma, me ka ʻike kikoʻī o 96.7% a me ka sensitivity o 87.0% (Figure 4A), a me kahi hana ʻokoʻa no ka pae I maʻi kanesa27.HIST1H4F he kiko'ī o 96.5% a me ka sensitivity o 85.4% no NSCLC, a me 96.5% a me 95.7%, no ka SCLC27.Eia hou, ua hōʻoia nā laʻana o nā ʻano maʻi maʻi ʻewalu ʻē aʻe, me ka maʻi maʻi pancreatic a me ka colorectal, ua hypermethylated ʻo HIST1H4F i nā ʻano ʻewalu a pau27.

Ka maʻi maʻi ʻāʻī

ʻO ka maʻi ʻaʻai ʻāʻī ka ʻehā o ka maʻi maʻi maʻi pinepine a ʻo ka ʻehā ke kumu nui o ka make ʻana o ka maʻi kanesa i nā wahine ma 2020, ʻo ia ka 3.1% o nā hihia hou a me 3.4% o nā make pili i ka maʻi kanesa ma ka honua1.No ka hoʻopau ʻana i ka maʻi maʻi cervical ma 2030, e like me ka manaʻo o ka WHO, he mea pono ka ʻike mua ʻana i ka maʻi maʻi cervical.Inā ʻike ʻia i ka wā mua, hiki i ka 5 mau makahiki ke ola ola i ka 92% me ka maʻi maʻi maʻi maʻi invasive41.Hōʻike nā alakaʻi alakaʻi o ka American Cancer Society (ACS) i nā ho'āʻo cytology cervical, nā ho'āʻo HPV mua, a i ʻole nā hōʻike no ka screening42.He invasive ka Cervical cytology a hiki ke ʻike i 63.5% wale nō o nā hihia CIN2+37.

ʻOi aku ka maikaʻi o ka PCDHGB7 me ka hoʻohana ʻana i nā pap Pap a me nā huna huna, a hiki ke hoʻokaʻawale maikaʻi i ka HSIL mai ka LSIL i kahi pae mua loa.ʻO PCDHGB7 wale nō ka sensitivity o 100.0% a me kahi kikoʻī o 88.7% no ka maʻi maʻi cervical (Figure 4B), a me kahi 82.1% sensitivity a me 88.7% kikoʻī no nā HSIL+ samples30.Loaʻa iā PCDHGB7 ka 90.9% sensitivity a me 90.4% kikoʻī i nā laʻana huna huna no ka maʻi maʻi cervical, ʻoi aku ka maʻalahi o ka ʻohi ʻana30.Ke hui pū ʻia me ka hoʻāʻo HPV kiʻekiʻe (hr) a i ʻole Thinprep Cytology Test (TCT), ʻoi aku ka nui o ka naʻau o ka PCDHGB7 o 95.7% a me ka kikoʻī o 96.2%, ʻoi aku ka nui ma mua o ka hōʻike hrHPV (20.3%), TCT (51.2%). ), a ʻo nā mea ʻelua i hui pū ʻia (57.8%) no ka maʻi maʻi cervical30.Ua hōʻike ʻia ʻo PCDHGB7 i hypermethylated i nā ʻano maʻi maʻi 17 mai ka waihona TCGA, e hōʻike ana i kona kūpono i ka ʻohana UCOM30.

Kiʻi 4 UCOM ua hōʻoia ʻia i nā ʻano maʻi maʻi ʻehā i loko o nā haʻawina lapaʻau nui.A. Hana 'ia o HIST1H4F, he UCOM, i ka 'ike 'ana i ka ma'i 'a'ai o 508 mau la'ana.B. Ka hana o PCDHGB7, he UCOM, i ka ʻike ʻana i ka maʻi maʻi ʻōpū o 844 mau laʻana.C. Hana ana o PCDHGB7, he UCOM, ma ka ike ana i ka ma'i ma'i ma'i endometrial o 577 mau la'ana palaki endometrial Pap a me Tao.D. Hana o SIX6, he UCOM, i ka urothelial cancer detection of 177 samples.

ʻO EC kekahi o nā maʻi maʻi maʻi maʻamau o ka ʻōnaehana hānau wahine ma ka honua holoʻokoʻa, me ka 4.2 miliona mau hihia hou a me 1% o nā make pili i ka maʻi kanesa i kēlā me kēia makahiki1.Me ka hoʻomaʻamaʻa kūleʻa ma ka pae mua, hiki ke hoʻōla ʻia ʻo EC a he 5 mau makahiki ola ola o 95% no ka maʻi maʻi maʻi pae I.ʻO nā poʻe maʻi i hōʻailona ʻia, e like me ke kahe ʻana o ka ʻōpū, loaʻa iā lākou ka loiloi lāʻau lapaʻau i kēlā me kēia manawa a hana i nā kaʻina biopsy invasive a ʻeha, ʻoiai he 5%-10% wale nō ka hoʻomohala ʻana i ka EC43.ʻAʻole hiki ke hoʻokaʻawale i nā loli endometrial maikaʻi mai nā hoʻololi endometrial maʻamau a me ka helu false-positive kiʻekiʻe44.

ʻO kahi hoʻohālikelike like o ka serum CA-125, kahi biomarker EC i hoʻokō nui ʻia, a me PCDHGB7 i alakaʻi ʻia.He 24.8% ka naʻau o ka Serum CA-125, e hōʻike ana he hōʻailona kūpono ʻole ʻo CA-125 no EC me kahi kikoʻī o 92.3%31.ʻO ka ʻike ʻana i ka PCDHGB7 me ka hoʻohana ʻana i nā laʻana palaki Pap i loaʻa i kahi sensitivity o 80.65% a me kahi kikoʻī o 82.81% no nā pae ECatall, ʻoiai he 61.29% ka manaʻo o ka polu Tao a me kahi kikoʻī o 95.31%31.ʻO ka PCDHGB7 diagnostic model, i hoʻokumu ʻia ma Me-qPCR, ua hāʻawi mai i kahi sensitivity o 98.61%, kahi kikoʻī o 60.5%, a me ka pololei holoʻokoʻa o 85.5%, me ka hoʻohana ʻana i nā laʻana palaki Pap a me Tao (Figure 4C)31.

Ka maʻi ʻaʻai ʻurothelial

ʻO ka maʻi maʻi ʻaʻai Urothelial, ʻo ia hoʻi nā maʻi maʻi ʻaʻai, renal pelvis, a me ka ureter cancer, ʻo ia ka hiku o ka maʻi maʻi maʻi pinepine loa i ka makahiki 2020 a puni ka honua, he 5.2% o nā maʻi hou a me 3.9% o ka make1.ʻO nā maʻi maʻi ʻaʻai Urothelial, ʻoi aku ka nui ma mua o 50% o ka maʻi maʻi maʻi maʻi, ʻo ia ka hā o ka maʻi maʻi maʻi pinepine loa i ʻAmelika Hui Pū ʻIa i ka makahiki 2022, ʻo ia ka 11.6% o nā hihia hou i ʻike ʻia3.Ma kahi o 75% o nā maʻi maʻi maʻi ʻaʻai i hoʻokaʻawale ʻia ma ke ʻano he maʻi maʻi maʻi ʻaʻa ʻole i hoʻopaʻa ʻia i ka mucosa a i ʻole submucosa45.ʻO ka biopsy cystoscopy ke kūlana gula no ka ʻike ʻana i ka maʻi maʻi urothelial i hoʻokō ʻia e ka fluorescence in situ hybridization (FISH) a me nā hoʻokolohua cytology.ʻAʻole maikaʻi ka hana diagnostic i ka FISH a me ka cytology, a ʻo ka cystoscopy ka mea hoʻopiʻi a loaʻa ke kumu o ka nalo ʻana o nā microlesions, ka wehewehe hewa ʻana i nā ʻeha, a hiki ke hoʻolaha a hoʻihoʻi hou i ka maʻi kanesa46.ʻO ka UCOM i hōʻoia mua ʻia, PCDHGB7, ua hōʻike pū ʻia he hypermethylated i ka maʻi maʻi urothelial, me kahi wahi ma lalo o ka pihi o 0.86, e hōʻike ana i kahi hiki ke hoʻomaʻamaʻa diagnostic30.No ka hōʻoia hou ʻana i nā UCOM a ʻoi aku ka maikaʻi o ka hoʻokipa ʻana i nā ʻano laʻana, ua nānā ʻia ʻo SIX6, kahi moʻolelo UCOM, a hōʻike i ka hiki ke diagnostic maikaʻi loa i ka ʻike mua ʻana i ka maʻi maʻi urothelial me ka hoʻohana ʻana i nā laʻana mimi ma ka platform Me-qPCR.ʻO ka ʻike ʻana ʻo SIX6 me ka hoʻohana ʻana i nā laʻana mimi ua hōʻike ʻia kahi ʻike hoʻokūkū o 86.7% a me kahi kikoʻī o 90.8% (Figure 4D), ʻoiai ʻaʻole invasive a maʻalahi ke loaʻa32.Ke noiʻi ʻia nei ka mana o SIX6 i ka nānā ʻana i ka metastasis a me ka loiloi ʻana i ka maikaʻi o ka mālama ʻana.

ʻO ka wā e hiki mai ana a me nā pilikia

He hana koʻikoʻi ko UCOM i ka hiki ke diagnostic o nā maʻi maʻi he nui, akā nui nā hana i koe e hana.Ke hoʻonui nei mākou i ka papa inoa o nā UCOM a ke hōʻoia nei mākou i nā UCOM i nā ʻano maʻi maʻi ʻē aʻe, me nā mea maʻamau paʻakikī ke ʻike.Ua hoʻokūpaʻa hou nā hopena hōʻoia mai nā ʻikepili TCGA i ka noi ʻana o nā UCOM i nā ʻano maʻi kanesa a me nā kūlana hou aʻe.Ma kahi hoʻokolokolo hoʻomaka, ua hōʻike ʻia nā UCOM i ka hiki ke diagnostic no ka cholangiocarcinomas a me ka pancreatic adenocarcinomas, kahi kokoke hiki ʻole ke ʻike i ka wā mua me nā kaʻina screening o kēia manawa32,47.Hiki ke hoʻohana ʻia ka hiki ke ʻike i nā maʻi maʻi maʻi kakaʻikahi me nā UCOM me ka DNA tumor circulating (ctDNA) e kahi platform biopsy wai i hoʻomaikaʻi ʻia48.ʻO kahi haʻawina e pili ana i kahi pānaʻi ʻike pan-cancer i hoʻokumu ʻia i ka plasma DNA i hāʻawi mai i kahi naʻau o 57.9%49.ʻOiai ke kūlana kiʻekiʻe, hōʻike ka hana holoʻokoʻa aia kahi lumi no ka hoʻomaikaʻi ʻana.

Ua kākoʻo pū nā hiʻohiʻona kūʻokoʻa o nā UCOM i ka hoʻokolokolo ʻana o ka hiki ʻana o ka UCOM i ka loiloi ʻana i ka maikaʻi o ka mālama ʻana a me ka nānā hou ʻana.Wahi a ka Response Evaluation Criteria in Solid Tumors (RECIST), ʻo ke kiʻi ʻana i ka lāʻau lapaʻau ke ʻano i manaʻo ʻia no ka nānā hou ʻana a me ka loiloi ʻana i ka maikaʻi o ka mālama ʻana, ʻoiai hoʻohana wale ʻia nā hōʻailona tumo no ka loiloi50.ʻO kaʻoiaʻiʻo, akā naʻe, ua hoʻopilikia nuiʻia nā ala kiʻi kiʻi e ka pinepine a me ka manawa, a no laila e hōʻike i nā maʻi i ka pilikia a me nā koina51,52.Ua hōʻoia ʻia ʻo SIX6 e lawelawe ma ke ʻano he wānana no ka metastasis maʻi maʻi umauma32.ʻO ka nānā ʻana i ka ctDNA e pili ana i ka wai biopsy hiki ke nānā i ka manawa maoli ma luna o nā mahina maʻi koena liʻiliʻi ma mua o ka ʻike radiologic, ke hoʻopanee maikaʻi a me ka pale ʻana i ka piʻi ʻana o ka maʻi maʻi e pili ana i ka relapse53.Hōʻike nā hopena mua e hōʻike ana nā UCOM i ke kiʻekiʻe o ka hypermethylation maʻi maʻi i ka manawa maoli ma hope koke o ka ʻoki ʻana a me ka mālama ʻana32.ʻO ka ʻike kiʻekiʻe i hōʻike ʻia e nā UCOM a me ka hoʻohana ʻana i nā ʻano laʻana non-intrusive he nui e hiki ai i nā UCOM ke lawelawe ma ke ʻano he biomarker kiaʻi hou ʻana me ka mālama ʻana i ka hoʻomanawanui kiʻekiʻe.

I ka manawa like, ʻo ka hiki ʻana o ka lehulehu i ka hoʻāʻo kekahi pilikia nui e pono ai ka hoʻoikaika hou.ʻOiai ua hoʻohana ʻia nā hui ʻike UCOM i nā halemai hou aʻe i ka manaʻolana e pōmaikaʻi hou aku i nā maʻi, ua hana ikaika ʻia nā ʻike pro bono a me nā nānā ʻana ma ke kuaʻāina ʻo Kina.Pono nā UCOM i ka hoʻonui ʻia ʻana o ka hiki ke hoʻokō ʻia ma ke ʻano he hāmeʻa screening hiki ke kūpono, ʻoi aku hoʻi no nā wahi underdeveloped.

ʻOiai ke hoʻohiki nei ka noi UCOM i ka ʻike mua ʻana, nui nā mea ʻike ʻole e pili ana iā UCOM.Me ka ʻimi hoʻoikaika ʻana, ʻae ʻia ka noiʻi hou e pili ana i ke kumu o ka UCOM ma ke ao holoʻokoʻa i nā maʻi maʻi.Pono e hoʻokolokolo hou ʻia nā ʻōnaehana hoʻoponopono epigenetic ma lalo o nā UCOM, hiki ke hōʻoia i kahi kuhikuhi hou no nā lāʻau lapaʻau maʻi maʻi.Ke hoʻi nei i ka pilina ma waena o ka homogeneity tumo a me ka heterogeneity, makemake mākou i ke kumu e hiki ai i nā UCOM ke lilo i mea ʻokoʻa i ka hapa nui o nā biomarkers maʻi kanesa i pili paʻa i nā ʻano maʻi maʻi maʻi.ʻAʻole i hoʻoholo ʻia ke kuleana o ka UCOM-identified DNA methylation aber-rations in tumorigenesis, tumor progression, and metastasis i ke kaʻina hana o ka nalowale a loaʻa hou i ka ʻike cell a pono e nānā pono.ʻO kekahi hoihoi nui aia i ka laulā o ka hoʻohui ʻia ʻana o ka ʻano homogeneity o UCOMs me nā kiko-ʻokoʻa hōʻailona i ka manaʻolana e hoʻokokoke pololei ana i nā ʻano maʻi kanesa a me ka ʻike ʻana i ke kumu o ka ʻiʻo maʻi ma ke ʻano hoʻohuli.Hiki i nā UCOM ke lilo i mea hana kūpono no ka pale ʻana i ka maʻi kanesa, ʻike i ka maʻi kanesa, a hiki ke pale a hoʻopau i ka maʻi kanesa.

Hāʻawi i ke kākoʻo

Ua kākoʻo ʻia kēia hana e ka National Key R&D Program of China (Grant No. 2022BEG01003), ka National Natural Science Foundation of China (Grant Nos. 32270645 a me 32000505), he Grant mai Heilongjiang Provincial Health Commission (Grant No. 2020-111) , a he haʻawina mai Heze Science and Technology Institute (Grant No. 2021KJPT07).

ʻO ka ʻōlelo kūʻē o ka hoihoi

ʻO Wei Li ka Luna Hoʻokele R&D no Shanghai Epiprobe Biotechnology Co., Ltd. Ua lawelawe ʻo Wenqiang Yu ma ka Papa Kūkākūkā Scientific o Epiprobe.Ua ʻae ʻo W. Yu a me Epiprobe i nā patent e kali nei e pili ana i kēia hana.Hōʻike nā mea kākau ʻē aʻe ʻaʻohe makemake hoʻokūkū.

Nā hāʻawi a ka mea kākau

Hoʻokumu a hoʻolālā i ka papahana: Chengchen Qian a me Wenqiang Yu.

Ua kākau i ka pepa: Chengchen Qian.

Hana i nā kiʻi: Chengchen Qian.

Nānā a hoʻoponopono i ka manuscript: Xiaolong Zou, Wei Li, Yinshan Li a me Wenqiang Yu.

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E haʻi i kēia ʻatikala e like me: Qian C, Zou X, Li W, Li Y, Yu W. ʻO ka outpost e kūʻē i ka maʻi kanesa: nā hōʻailona maʻi āpau āpau.ʻO ka Cancer Biol Med.2023;20: 806-815.

doi: 10.20892/j.issn.2095-3941.2023.0313

Ka manawa hoʻouna: Mei-07-2024

ʻO ka outpost e kūʻē i ka maʻi kanesa: nā hōʻailona wale nō ka maʻi kanesa āpau