Kafukufuku wopitilira muyeso: Ukadaulo wopangidwa ndi PCR-based blood ctDNA methylation umatsegula nyengo yatsopano yaulonda wa MRD wa khansa ya colorectal.

Posachedwapa, JAMA Oncology (IF 33.012) adasindikiza zotsatira zofufuza zofunika [1] ndi gulu la Prof. Cai Guo-ring kuchokera ku Cancer Hospital of Fudan University ndi Prof. Wang Jing wochokera ku Renji Hospital ku Shanghai Jiao Tong University School of Medicine, mogwirizana ndi KUNYUAN BIOLOGY: "Kuzindikira Koyambirira kwa Molecular Resigement Residual Residual Cancer III Kuzungulira kwa Chotupa cha DNA Methylation ndi Risk Stratification) ”. Kafukufukuyu ndi kafukufuku woyamba padziko lonse lapansi wogwiritsa ntchito ukadaulo wa PCR-based blood ctDNA multigene methylation kulosera za khansa ya colorectal ndikuwunikanso kuyambiranso, kumapereka njira yotsika mtengo yaukadaulo ndi yankho poyerekeza ndi njira zomwe zilipo kale zaukadaulo wa MRD, zomwe zikuyembekezeka kupititsa patsogolo kwambiri kugwiritsa ntchito kwachipatala kwa khansa yapakhungu komanso kuwongolera moyo wabwino, komanso kuwongolera moyo wabwino. Kafukufukuyu adawunikidwanso kwambiri ndi magaziniyi ndi akonzi ake, ndipo adalembedwa ngati pepala lofunikira kwambiri pankhaniyi, ndipo Pulofesa Juan Ruiz-Bañobre waku Spain ndi Pulofesa Ajay Goel waku United States adaitanidwa kuti akawunikenso. Kafukufukuyu adanenedwanso ndi GenomeWeb, media media media ku United States.

Khansara ya colorectal (CRC) ndi chotupa choyipa chofala cham'mimba ku China. Zambiri za 2020 International Agency for Research on Cancer (IARC) zikuwonetsa kuti milandu yatsopano ya 555,000 ku China imakhala pafupifupi 1/3 yapadziko lonse lapansi, pomwe chiwopsezo chikudumphira pamalo achiwiri a khansa wamba ku China; Imfa 286,000 ndi pafupifupi 1/3 yapadziko lonse lapansi, yomwe ili ngati yachisanu yomwe imayambitsa kufa kwa khansa ku China. Chifukwa chachisanu cha imfa ku China. Ndizofunikira kudziwa kuti mwa odwala omwe ali ndi matenda, TNM stage I, II, III ndi IV ndi 18.6%, 42.5%, 30.7% ndi 8.2% motsatira. Oposa 80% ya odwala ali pakati ndi mochedwa magawo, ndipo 44% ya iwo ali ndi metastases pa nthawi imodzi kapena heterochronic kutali ndi chiwindi ndi mapapo, zomwe zimakhudza kwambiri nthawi yopulumuka, kuyika thanzi la anthu athu pangozi ndikupangitsa kuti anthu azikhala ndi mavuto ambiri azachuma. Malinga ndi ziwerengero za National Cancer Center, pafupifupi pachaka kuwonjezeka mtengo wa mankhwala khansa colorectal ku China ndi za 6.9% mpaka 9.2%, ndi munthu thanzi ndalama odwala mkati chaka chimodzi matenda akhoza kutenga 60% ya ndalama banja. Odwala khansa akudwala matendawa komanso akuvutika kwambiri zachuma [2].
Makumi asanu ndi anayi pa zana aliwonse a zotupa za khansa ya m'matumbo amatha kuchotsedwa opaleshoni, ndipo chotupacho chikazindikirika koyambirira, kuchuluka kwa kupulumuka kwazaka zisanu pambuyo pochitidwa opaleshoni yoopsa, koma kuchuluka kwa kubwereza pambuyo pakuchotsa kwakukulu kumakhalabe pafupifupi 30%. Zaka zisanu zakupulumuka kwa khansa ya colorectal mwa anthu aku China ndi 90.1%, 72.6%, 53.8% ndi 10.4% pamagawo I, II, III ndi IV, motsatana.
Minimal residual disease (MRD) ndi chifukwa chachikulu cha chotupa choyambiranso pambuyo pa chithandizo chamankhwala. M'zaka zaposachedwa, ukadaulo wozindikira matenda a MRD wa zotupa zolimba zapita patsogolo mwachangu, ndipo kafukufuku wambiri wowunikira komanso wolowererapo watsimikizira kuti mawonekedwe a MRD pambuyo pa opaleshoni amatha kuwonetsa chiwopsezo cha kuyambiranso kwa khansa ya colorectal pambuyo pa opaleshoni. Kuyezetsa kwa ctDNA kuli ndi ubwino wokhala wosasokoneza, wosavuta, wofulumira, wopezeka ndi zitsanzo zambiri komanso kugonjetsa kusiyanasiyana kwa chotupa.
Upangiri waku US NCCN wa khansa ya m'matumbo ndi malangizo aku China CSCO a khansa yapakhungu onse amati pakuwunika kwapambuyo kwapang'onopang'ono komanso kusankha adjuvant chemotherapy mu khansa ya m'matumbo, kuyezetsa kwa ctDNA kungapereke chidziwitso chodziwikiratu komanso cholosera kuti chithandizire pazisankho za chithandizo cha adjuvant kwa odwala omwe ali ndi khansa ya m'matumbo II kapena III. Komabe, maphunziro ambiri omwe alipo amayang'ana pa kusintha kwa ctDNA kutengera luso lapamwamba la sequencing (NGS), lomwe liri ndi njira yovuta, nthawi yayitali, komanso mtengo wokwera [3], ndi kusowa pang'ono kwa generalizability ndi kuchepa kochepa pakati pa odwala khansa.
Pankhani ya odwala omwe ali ndi khansa ya colorectal stage III, kuwunika kwamphamvu kwa ctDNA kochokera ku NGS kumawononga ndalama zokwana $10,000 paulendo umodzi ndipo kumafuna nthawi yodikirira mpaka milungu iwiri. Ndi mayeso a multigene methylation mu kafukufukuyu, ColonAiQ®, odwala amatha kukhala ndi kuwunika kwamphamvu kwa ctDNA pamtengo wakhumi ndikupeza lipoti pakangotha ​​masiku awiri.
Malinga ndi milandu 560,000 yatsopano ya khansa ya colorectal ku China chaka chilichonse, odwala omwe ali ndi khansa yapakatikati ya II-III (gawoli ndi pafupifupi 70%) amafunikira kuwunika mwachangu, ndiye kukula kwa msika wa kuwunika kwamphamvu kwa MRD khansa yapakhungu imafikira mamiliyoni a anthu chaka chilichonse.
Zitha kuwoneka kuti zotsatira za kafukufuku zili ndi zofunikira zasayansi komanso zothandiza. Kupyolera mu maphunziro akuluakulu azachipatala omwe akuyembekezeka, zatsimikizira kuti ukadaulo wa PCR-based blood ctDNA multigene methylation ukhoza kugwiritsidwa ntchito poneneratu za kuyambiranso kwa khansa yapakhungu komanso kuyang'anira kubweranso ndi chidwi, nthawi yake komanso kugwiritsa ntchito bwino ndalama, kupangitsa kuti mankhwala olondola apindule kwambiri odwala khansa. Phunziroli likuchokera ku ColonAiQ®, kuyesa kwamitundu yambiri ya methylation ya khansa ya colorectal yopangidwa ndi KUNY, yomwe ntchito yake yachipatala imafunika pakuwunika koyambirira ndi kuzindikira kwatsimikiziridwa ndi kafukufuku wapakati wachipatala.
Gastroenterology (IF33.88), nyuzipepala yapamwamba yapadziko lonse yokhudzana ndi matenda a m'mimba mu 2021, inanena zotsatira za kafukufuku wambiri wa Zhongshan Hospital of Fudan University, Cancer Hospital of Fudan University ndi mabungwe ena ovomerezeka azachipatala mogwirizana ndi KUNYAN Biological, yomwe inatsimikizira kuti ColonAiQ® ChangAiQ® ChangAiQ ® ChangAiQ ® ndi kufufuza koyambirira kwa khansa ya m'mapapo. amawunikanso momwe angagwiritsire ntchito pakuwunika kwa khansa ya colorectal.

Pofuna kutsimikiziranso kugwiritsa ntchito kwachipatala kwa ctDNA methylation pakuyika pachiwopsezo, zisankho zowongolera komanso kuyang'anira kuyambiranso koyambirira mu siteji ya I-III ya khansa ya colorectal, gulu lofufuza lidaphatikiza odwala 299 omwe ali ndi khansa yapakatikati ya I-III omwe adachitidwa opaleshoni yayikulu ndikusonkhanitsa zitsanzo zamagazi potsatira (miyezi itatu motalikirana, opareshoni ya mwezi umodzi isanakwane) mkati mwa sabata limodzi pambuyo pa opaleshoni. kuyezetsa magazi kwa ctDNA.
Choyamba, zidapezeka kuti kuyezetsa kwa ctDNA kumatha kuneneratu za chiopsezo chobwereranso kwa odwala khansa ya colorectal koyambirira, asanachitike komanso asanachitike opaleshoni. Odwala omwe ali ndi preoperative ctDNA-positive anali ndi mwayi wochulukirapo kuposa odwala omwe alibe ctDNA-negative (22.0%> 4.7%). Kuyesa koyambirira kwa ctDNA kunaneneratu za chiopsezo chobwereza: mwezi umodzi pambuyo pa kuchotsedwa kwakukulu, odwala omwe ali ndi ctDNA anali ndi mwayi wobwereza maulendo 17.5 kuposa odwala oipa; gululo linapezanso kuti kuyesa kwa ctDNA ndi CEA kophatikizana kunapititsa patsogolo ntchito pang'ono pozindikira kubwereza (AUC = 0.849), koma kusiyana kwake sikunali kwakukulu poyerekeza ndi kuyesa kwa ctDNA (AUC = 0.839) kokha Kusiyana kwake sikunali kwakukulu poyerekeza ndi ctDNA yokha (AUC = 0.839).
Magawo azachipatala ophatikizidwa ndi ziwopsezo pakali pano ndiye maziko akulu owopsa a odwala khansa, ndipo m'malingaliro apano, odwala ambiri amabwereranso [4], ndipo pakufunika kufunikira kwa zida zabwinoko za stratification monga chithandizo chopitilira muyeso komanso chithandizo chocheperako chikukhalira limodzi kuchipatala. Kutengera izi, gululi lidayika odwala omwe ali ndi khansa ya colorectal siteji yachitatu m'magulu osiyanasiyana kutengera kuwunika kwachiwopsezo cha chipatala (T4 / N2) ndi chiopsezo chochepa (T1-3N1)) ndi nthawi ya chithandizo cha adjuvant (miyezi 3/6). Kufufuzaku kunapeza kuti odwala omwe ali m'gulu la odwala omwe ali ndi chiopsezo chachikulu cha ctDNA anali ndi chiwerengero chochepa chobwereza ngati alandira miyezi isanu ndi umodzi ya chithandizo chamankhwala; mu gulu laling'ono lachiopsezo la odwala ctDNA-positive, panalibe kusiyana kwakukulu pakati pa chithandizo cha adjuvant ndi zotsatira za odwala; pomwe odwala omwe alibe ctDNA anali ndi chidziwitso chabwinoko kuposa odwala omwe ali ndi ctDNA komanso nthawi yayitali yobwerezabwereza (RFS); siteji I ndi otsika chiopsezo siteji II khansa yapakhungu Onse odwala ctDNA alibe analibe kuyambiranso mkati zaka ziwiri; Chifukwa chake, kuphatikiza kwa ctDNA ndi mawonekedwe azachipatala kukuyembekezeka kupititsa patsogolo kusanja kwachiwopsezo ndikulosera bwino kubwereza.

Chithunzi 1. Kusanthula kwa Plasma ctDNA ku POM1 kuti azindikire msanga za khansa yapakhungu.
Zotsatira zina za kuyezetsa kwamphamvu kwa ctDNA zikuwonetsa kuti chiopsezo chobwereranso chinali chokwera kwambiri kwa odwala omwe ali ndi kuyezetsa kwamphamvu kwa ctDNA kuposa odwala omwe ali ndi ctDNA yoyipa panthawi yanthawi yowunikiranso matenda pambuyo pa chithandizo chotsimikizika (pambuyo pa opaleshoni yayikulu + adjuvant therapy) (Chithunzi 3ACD), komanso kuti ctDNA imatha kuwonetsa kuthekera kwa chotupa kuyambiranso mpaka miyezi 20 yoyambirira kubwereza ndi kulowererapo panthawi yake.

Chithunzi 2. Kusanthula kwa ctDNA kutengera gulu lalitali kuti lizindikire kuyambiranso kwa khansa ya colorectal.

"Maphunziro ambiri omasulira a khansa yapakhungu amatsogolera kulanga, makamaka kuyezetsa kwa MRD kochokera ku ctDNA kukuwonetsa kuthekera kwakukulu kopititsa patsogolo kasamalidwe ka odwala khansa ya colorectal pambuyo pochita opaleshoni popangitsa kuti pakhale chiwopsezo chobwerezabwereza, kuwongolera zisankho zachipatala komanso kuyang'anira kuyambiranso koyambirira.

Ubwino wosankha DNA methylation ngati cholembera cha MRD pozindikira masinthidwe ndikuti sichifunikira kuwunika kwamtundu wonse wamtundu wa chotupa, imagwiritsidwa ntchito mwachindunji kuyezetsa magazi, ndikupewa zotsatira zabodza chifukwa chozindikira kusintha kwachilengedwe kochokera ku minofu yabwinobwino, matenda oopsa, ndi clonal hematopoiesis.
Kafukufukuyu ndi maphunziro ena okhudzana nawo amatsimikizira kuti kuyesa kwa ctDNA-based MRD ndiye chinthu chofunikira kwambiri chodziyimira pawokha pachiwopsezo cha siteji ya I-III ndipo chingagwiritsidwe ntchito kuthandizira kutsogolera zisankho zamankhwala, kuphatikiza "kukwera" ndi "kutsika" kwa adjuvant therapy MRD ndiye chinthu chofunikira kwambiri chodziyimira pawokha pachiwopsezo chobwereranso pambuyo pa opaleshoni ya siteji I-III colorectal cancer.
Munda wa MRD ukuyenda mwachangu ndi njira zingapo zatsopano, zowunikira komanso zowunikira zenizeni zochokera ku epigenetics (DNA methylation ndi fragmentomics) ndi ma genomics (kutsatizana kozama kwambiri kapena kutsata ma genome onse). Tikuyembekeza kuti ColonAiQ® ikupitiriza kupanga maphunziro akuluakulu azachipatala ndipo ikhoza kukhala chizindikiro chatsopano cha kuyezetsa kwa MRD komwe kumaphatikizapo kupezeka, kuchita bwino komanso kukwanitsa kukwanitsa komanso kungagwiritsidwe ntchito kwambiri pazochitika zachipatala."
Maumboni
[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. Kuzindikira Koyambirira kwa Maselo a Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Tumor. JAMA Oncol. 2023 Apr 20.
[2] "Mtolo wa matenda a khansa ya m'mimba mwa anthu aku China: kodi zasintha m'zaka zaposachedwa? , Chinese Journal of Epidemiology, Vol. 41, No. 10, October 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Kutsatiridwa kwa m'badwo wotsatira wa DNA yozungulira-chotupa kuti ifufuze matenda ochepa otsalira mu khansa ya m'matumbo. Ann Oncol. Nov 1, 2019; 30 (11): 1804-1812.
[4] Taieb J, André T, Auclin E. Refining adjuvant therapy for non-metastatic colon cancer, miyezo yatsopano ndi malingaliro. Chithandizo cha Cancer Rev. 2019; 75:1-11.