He rangahau tirohanga hou: Ka whakatuwherahia e te hangarau methylation ctDNA toto e hangai ana ki te PCR tētahi wā hou o te tirotiro MRD mō te mate pukupuku koroni

Nō nā tata nei, i whakaputa a JAMA Oncology (IF 33.012) i tētahi hua rangahau nui [1] nā te tīma o Ahorangi Cai Guo-ring o te Hōhipera Matepukupuku o te Whare Wānanga o Fudan me Ahorangi Wang Jing o te Hōhipera Renji o te Kura Hauora o te Whare Wānanga o Shanghai Jiao Tong, i te mahi tahi me KUNYUAN BIOLOGY: "Te Kitenga Moata o te Mate Toenga Molecular me te Whakarōpūtanga Mōrearea mō te Wahanga I ki te III Matepukupuku Colorectal mā te Circulating Tumor DNA Methylation me te Whakarōpūtanga Mōrearea)". Ko tēnei rangahau te rangahau maha-pokapū tuatahi o te ao ki te whakamahi i te hangarau methylation multigene ctDNA toto e hangai ana ki te PCR mō te matapae me te aroturuki i te hokinga mai o te matepukupuku colorectal, e whakarato ana i tētahi ara hangarau me te otinga utu-pai ake i whakaritea ki ngā tikanga hangarau kitenga MRD o nāianei, e tumanakohia ana ka whakapai ake i te whakamahinga haumanu o te matapae me te aroturuki i te hokinga mai o te matepukupuku colorectal, ā, ka whakapai ake i te oranga me te kounga o te oranga o te tūroro. I arotakehia nuitia hoki te rangahau e te hautaka me ōna ētita, ā, i whakarārangihia hei pepa taunakitanga matua i roto i tēnei putanga, ā, i karangatia a Ahorangi Juan Ruiz-Bañobre o Pāniora me Ahorangi Ajay Goel o te Hononga o Amerika ki te arotake. I tukuna anō te pūrongo mō te rangahau e GenomeWeb, he pāpāho koiora matua i te Hononga o Amerika.

Ko te mate pukupuku repeure (CRC) he pukupuku kino noa o te ara kai i Haina. E whakaatu ana ngā raraunga o te Tari Rangahau Mate Pukupuku o te Ao (IARC) o te tau 2020, e 555,000 ngā kēhi hou i Haina, tata ki te 1/3 o te ao, ā, ko te reiti mate pukupuku noa i Haina e piki ana ki te tuarua o ngā tūranga o ngā mate pukupuku noa; 286,000 ngā mate, tata ki te 1/3 o te ao, ko te tuarima o ngā take tino nui o ngā mate pukupuku i Haina. Ko te tuarima o ngā take mate i Haina. He mea nui kia mōhiotia i roto i ngā tūroro kua tātaritatia, ko ngā wāhanga TNM I, II, III me IV he 18.6%, 42.5%, 30.7% me te 8.2% ia. Neke atu i te 80% o ngā tūroro kei roto i ngā wāhanga waenga me ngā wāhanga mutunga, ā, 44% o rātou he metastases tawhiti i te wā kotahi, heterochronic rānei ki te ate me te pukahukahu, e tino pā kino ana ki te wā ora, e whakararu ana i te hauora o ō tātou kainoho, ā, he taumaha te taumahatanga pāpori me te ōhanga. E ai ki ngā tatauranga o te National Cancer Center, ko te pikinga toharite ā-tau o te utu maimoatanga mate pukupuku koroni i Haina he tata ki te 6.9% ki te 9.2%, ā, ko te whakapaunga hauora whaiaro a ngā tūroro i roto i te tau kotahi o te tātaritanga ka taea te tango i te 60% o te moni whiwhi a te whānau. Kei te pāngia ngā tūroro mate pukupuku e te mate, ā, kei raro hoki i te pēhanga nui ohaoha [2].
E iwa tekau ōrau o ngā whara o te mate pukupuku koroni ka taea te tango mā te pokanga, ā, ki te kitea wawetia te pukupuku, ka teitei ake te reiti oranga mō ngā tau e rima i muri i te tangohanga nui, engari ko te reiti hokinga mai whānui i muri i te tangohanga nui kei te tata tonu ki te 30%. Ko ngā reiti oranga mō ngā tau e rima o te mate pukupuku koroni i roto i te taupori Haina he 90.1%, 72.6%, 53.8% me te 10.4% mō ngā wāhanga I, II, III me te IV.
Ko te mate toenga iti (MRD) tētahi tino take o te hokinga mai o te pukupuku i muri i te maimoatanga whānui. I ngā tau tata nei, kua tere te whanaketanga o te hangarau kimi MRD mō ngā pukupuku totoka, ā, kua whakaūhia e ētahi rangahau tirotiro me te wawaotanga taumaha ko te tūnga MRD i muri i te pokanga ka taea te tohu i te mōrearea o te hokinga mai o te mate pukupuku colorectal i muri i te pokanga. Ko ngā painga o te whakamātautau ctDNA he kore-whakaekenga, he māmā, he tere, he nui te urunga ki ngā tauira me te wikitoria i te rerekētanga o te pukupuku.
E kī ana ngā aratohu a te US NCCN mō te mate pukupuku koroni me ngā aratohu a te CSCO Hainamana mō te mate pukupuku koroni, mō te whakatau i te mōrearea o te hokinga mai i muri i te pokanga me te whiriwhiri i te chemotherapy adjuvant i roto i te mate pukupuku koroni, ka taea e te whakamātautau ctDNA te whakarato i ngā mōhiohio matapae me te matapae hei āwhina i ngā whakatau maimoatanga adjuvant mō ngā tūroro he mate pukupuku koroni wāhanga II, III rānei. Heoi, ko te nuinga o ngā rangahau o nāianei e aro ana ki ngā whakarerekētanga ctDNA i runga i te hangarau raupapatanga tere-rahi (NGS), he tukanga uaua, he roa te wā arahi, he nui te utu [3], me te kore e taea te whakawhānui ake me te iti o te horapa i waenga i ngā tūroro mate pukupuku.
Mō ngā tūroro mate pukupuku koroni wāhanga III, ko te utu mō te aroturuki hihiri ctDNA e ahu mai ana i te NGS tae atu ki te $10,000 mō te haerenga kotahi, ā, e rua wiki te roa o te wā tatari. Mā te whakamātautau methylation maha-ira i roto i tēnei rangahau, ColonAiQ®, ka taea e ngā tūroro te aroturuki hihiri ctDNA i te whakatekau o te utu, ā, ka whiwhi pūrongo i roto i ngā rā e rua noa iho.
E ai ki ngā kēhi hou e 560,000 o te mate pukupuku koroni i Haina i ia tau, ko te nuinga o ngā tūroro haumanu he mate pukupuku koroni wāhanga II-III (ko te ōwehenga he tata ki te 70%) he nui ake te hiahia mō te aroturuki hihiri, ā, ko te rahi o te mākete o te aroturuki hihiri MRD o te mate pukupuku koroni e eke ana ki te miriona tāngata i ia tau.
Ka kitea te hiranga nui o ngā hua rangahau ki te pūtaiao me te mahi. Nā roto i ngā rangahau haumanu whānui, kua whakaūtia ka taea te whakamahi i te hangarau methylation multigene ctDNA toto e ahu mai ana i te PCR mō te matapae i te hokinga mai o te mate pukupuku colorectal me te aroturuki i te hokinga mai me te aro, te wā tika me te whai huatanga utu, kia pai ake ai te rongoā tika ki te whai hua ki te nuinga o ngā tūroro mate pukupuku. Ko te kaupapa o te rangahau ko ColonAiQ®, he whakamātautau methylation multi-gene mō te mate pukupuku colorectal i whakawhanakehia e KUNY, ko tōna uara tono haumanu i roto i te tirotiro wawe me te tautuhi mate kua whakaūtia e tētahi rangahau haumanu matua.
I te tau 2021, i ripoatahia e te Gastroenterology (IF33.88), te hautaka o te ao matua mō ngā mate puku, ngā hua rangahau maha-pokapū o te Hōhipera Zhongshan o te Whare Wānanga o Fudan, te Hōhipera Matepukupuku o te Whare Wānanga o Fudan me ētahi atu whare hauora whai mana i te taha o KUNYAN Biological, i whakaū i te mahi pai a ColonAiQ® ChangAiQ® i roto i te tirotiro wawe me te tautuhi wawe i te mate pukupuku colorectal, ā, i te tuatahi i tūhuratia te whakamahinga pea i roto i te aroturukitanga o te matapae o te mate pukupuku colorectal.

Hei whakamana anō i te whakamahinga haumanu o te methylation ctDNA i roto i te whakarōpūtanga mōrearea, te ārahi i ngā whakatau maimoatanga me te aroturukitanga wawe o te hokinga mai i te mate pukupuku colorectal wāhanga I-III, i whakaurua e te tīma rangahau he 299 ngā tūroro he mate pukupuku colorectal wāhanga I-III i pokangahia, ā, i kohia he tauira toto i ia wāhi whai muri (e toru marama te wehe) i roto i te wiki kotahi i mua i te pokanga, kotahi marama i muri i te pokanga, me te rongoā āwhina i muri i te pokanga mō te whakamātautau ctDNA toto hihiri.
Tuatahi, i kitea ka taea e te whakamātautau ctDNA te matapae i te mōrearea o te hokinga mai anō i roto i ngā tūroro mate pukupuku colorectal i te wā tōmua, i mua i te pokanga me te wā tōmua i muri i te pokanga. He nui ake te tūponotanga o te hokinga mai anō i muri i te pokanga o ngā tūroro ctDNA-pai i mua i te pokanga i ngā tūroro ctDNA-kino i mua i te pokanga (22.0% > 4.7%). I matapae tonu te whakamātautau ctDNA i muri i te pokanga i te mōrearea o te hokinga mai anō: kotahi te marama i muri i te tangohanga nui, he 17.5 ngā wā ka nui ake te tūponotanga o ngā tūroro ctDNA-pai ki te hoki mai anō i ngā tūroro kino; i kitea anō hoki e te tīma he paku pai ake te mahi a te whakamātautau ctDNA me te CEA i te kitenga i te hokinga mai anō (AUC=0.849), engari kāore i tino nui te rerekētanga ki te whakataurite ki te whakamātautau ctDNA (AUC=0.839) anake. Kāore i tino nui te rerekētanga ki te whakataurite ki te ctDNA anake (AUC=0.839).
Ko te whakatauranga haumanu me ngā āhuatanga mōrearea te pūtake matua mō te wehewehenga mōrearea o ngā tūroro mate pukupuku, ā, i roto i te tauira o nāianei, he nui tonu ngā tūroro e hoki mai ana [4], ā, he hiahia nui ki ngā taputapu wehewehenga pai ake i te mea kei te noho tahi te maimoatanga nui me te maimoatanga iti i roto i te whare hauora. I runga i tēnei, i whakarōpūhia e te tīma ngā tūroro me te mate pukupuku koroni wāhanga III ki ngā rōpū iti rerekē i runga i te aromatawai mōrearea hokinga mai haumanu (mōrearea nui (T4/N2) me te mōrearea iti (T1-3N1)) me te wā maimoatanga tāpiri (3/6 marama). I kitea e te tātaritanga he iti ake te auau hokinga mai o ngā tūroro i roto i te rōpū mōrearea nui o ngā tūroro ctDNA-pai mena i whiwhi rātou i te ono marama o te rongoā tāpiri; i roto i te rōpū mōrearea iti o ngā tūroro ctDNA-pai, kāore he rerekētanga nui i waenga i te huringa maimoatanga tāpiri me ngā putanga o te tūroro; i te mea he pai ake te matapae o ngā tūroro ctDNA-kore i ngā tūroro ctDNA-pai me te wā roa ake o te kore hokinga mai (RFS) i muri i te pokanga; te mate pukupuku koroni wāhanga I me te mōrearea iti wāhanga II Kāore he hokinga mai o ngā tūroro ctDNA-kore katoa i roto i ngā tau e rua; Nō reira, e tūmanakohia ana mā te whakaurunga o te ctDNA ki ngā āhuatanga haumanu ka pai ake te whakarōpūtanga mōrearea, ā, ka pai ake te matapae i te hokinga mai.

Pikitia 1. Tātaritanga ctDNA plasma i POM1 mō te kitenga wawe o te hokinga mai o te mate pukupuku colorectal
I whakaatuhia e ngā hua atu o te whakamātautau ctDNA hihiri he nui ake te mōrearea o te hokinga mai i roto i ngā tūroro he pai te whakamātautau ctDNA hihiri i ngā tūroro he kino te ctDNA i te wā e aroturukihia ana te hokinga mai o te mate i muri i te maimoatanga whakamutunga (whai muri i te pokanga nui + te rongoā āwhina) (Pikitia 3ACD), ā, ka taea e te ctDNA te tohu i te hokinga mai o te pukupuku tae atu ki te 20 marama i mua atu i te whakaahua (Pikitia 3B), e tuku ana i te āheinga ki te kite wawe i te hokinga mai o te mate me te wawaotanga i te wā tika.

Pikitia 2. tātaritanga ctDNA i runga i te rōpū roa hei kite i te hokinga mai o te mate pukupuku koroni

"He nui ngā rangahau rongoā whakamaori mō te mate pukupuku koroni e ārahi ana i te kaupapa, inā koa ko te whakamātautau MRD e hangai ana ki te ctDNA e whakaatu ana i te kaha nui ki te whakarei ake i te whakahaere muri i te pokanga o ngā tūroro mate pukupuku koroni mā te whakahohe i te wehewehenga mōrearea o te hokinga mai, te ārahi i ngā whakatau maimoatanga me te aroturuki wawe i te hokinga mai."

Ko te painga o te whiriwhiri i te methylation DNA hei tohu MRD hou i runga i te kimi i ngā whakarerekētanga ira, ko te kore e hiahiatia he tirotiro raupapatanga ira katoa o ngā kiko pukupuku, ka whakamahia tika mō te whakamātautau toto, ā, ka karo i ngā hua teka-pai nā te kitenga o ngā whakarerekētanga tinana e ahu mai ana i ngā kiko noa, ngā mate pai, me te hematopoiesis clonal.
E whakaū ana tēnei rangahau me ētahi atu rangahau e pā ana ko te whakamātautau MRD e hangai ana ki te ctDNA te mea tino nui mō te hokinga mai o te mate pukupuku colorectal wāhanga I-III, ā, ka taea te whakamahi hei ārahi i ngā whakataunga maimoatanga, tae atu ki te "whakapiki ake" me te "whakaheke iho" o te rongoā tāpiri. Ko te MRD te mea tino nui mō te hokinga mai i muri i te pokanga mō te mate pukupuku colorectal wāhanga I-III.
Kei te tere whanake te mara o te MRD me te maha o ngā whakamātautau auaha, tino tairongo, me te motuhake e hangai ana ki te epigenetics (DNA methylation me fragmentomics) me te genomics (te raupapatanga arotahi tino hohonu, te raupapatanga ira katoa rānei). E tumanako ana mātou ka haere tonu a ColonAiQ® ki te whakarite i ngā rangahau haumanu nui, ā, ka taea te noho hei tohu hou mō te whakamātautau MRD e whakakotahi ana i te urunga atu, te mahi teitei me te utu whaitake, ā, ka taea te whakamahi whānui i roto i ngā mahi haumanu o ia rā.
Ngā Tohutoro
[1] Mo S, Ye L, Wang D, Han L, Zhou S, Wang H, Dai W, Wang Y, Luo W, Wang R, Xu Y, Cai S, Liu R, Wang Z, Cai G. Te Kitenga Moata o te Mate Toenga o te Ngota me te Wehewehenga Mōrearea mō te Matepukupuku Repeure o te Wāhanga I ki te III mā te Methylation DNA Tumor Circulating. JAMA Oncol. 2023 Paenga-whāwhā 20.
[2] “Te taumahatanga o te mate pukupuku koroni i roto i te taupori Hainamana: kua rerekē i ngā tau tata nei? , Chinese Journal of Epidemiology, Vol. 41, Nama 10, Oketopa 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. I arotahi ki te raupapatanga o te reanga hou o te DNA pukupuku e rere ana hei aroturuki i te mate toenga iti i roto i te mate pukupuku koroni ā-rohe. Ann Oncol. Whiringa-ā-rangi 1, 2019;30(11):1804-1812.
[4] Taieb J, André T, Auclin E. Te whakatikatika i te rongoā āwhina mō te mate pukupuku koroni kāore i horapa, ngā paerewa hou me ngā tirohanga. Cancer Treat Rev. 2019;75:1-11.