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, mu mgwirizano ndi KUNYUAN BIOLOGY: "Kuzindikira Koyambirira kwa Matenda a Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer kudzera Kuzungulira Tumor DNA Methylation ndi Risk Stratification) ”. Kafukufukuyu ndi kafukufuku woyamba padziko lonse lapansi wogwiritsa ntchito ukadaulo wa PCR-based blood ctDNA multigene methylation kulosera za kuyambiranso kwa khansa ya colorectal komanso kuyang'anira kubweranso, kupereka njira yaukadaulo yotsika mtengo komanso yankho poyerekeza ndi njira zamakono zozindikirira za MRD, zomwe zikuyembekezeka. kuti apititse patsogolo kwambiri kagwiritsidwe ntchito kachipatala ka kuneneratu za kuyambiranso kwa khansa yapakhungu ndi kuwunika, komanso kusintha kwambiri moyo wa odwala komanso 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 apakati komanso mochedwa, ndipo 44% ya iwo amakhala ndi metastases yakutali kapena heterochronic ku chiwindi ndi mapapo, zomwe zimakhudza kwambiri nthawi yopulumuka, kuyika thanzi la anthu athu pachiwopsezo ndikuyambitsa mavuto azachuma komanso chikhalidwe cha anthu. katundu. Malinga ndi ziwerengero za National Cancer Center, pafupifupi chaka chilichonse chiwonjezeko chamtengo wa chithandizo cha khansa ya colorectal ku China ndi pafupifupi 6.9% mpaka 9.2%, ndipo ndalama zomwe odwala amawononga mkati mwa chaka chimodzi atazindikira matendawa zimatha kutenga 60% ya odwala. ndalama zabanja. 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.
Malangizo a US NCCN pa 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 zisankho zachipatala kwa odwala omwe ali ndi gawo lachiwiri. kapena III khansa ya m'matumbo. 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 yatsopano 560,000 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. Khansara ya m'mimba imafikira anthu mamiliyoni ambiri 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 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), magazini yapamwamba kwambiri padziko lonse lapansi pankhani ya matenda am'mimba mu 2021, inanena zotsatira za kafukufuku wambiri wa Zhongshan Hospital of Fudan University, Cancer Hospital of Fudan University ndi mabungwe ena azachipatala ovomerezeka molumikizana ndi KUNYAN Biological, zomwe zidatsimikizira. Kuchita bwino kwambiri kwa ColonAiQ® ChangAiQ® pakuwunika koyambirira komanso kuzindikira koyambirira kwa khansa ya colorectal, ndipo poyambirira adafufuza amawunikanso momwe angagwiritsire ntchito pakuwunika kowunika kwa khansa yapakhungu.

Pofuna kutsimikiziranso kugwiritsa ntchito kwachipatala kwa ctDNA methylation pakuyika pachiwopsezo, zisankho zotsogola komanso kuyang'anira kuyambiranso koyambirira mu siteji ya I-III ya khansa ya colorectal, gulu lofufuza lidaphatikiza odwala 299 omwe ali ndi siteji ya I-III ya khansa yapakhungu yomwe idachitidwa opaleshoni yowopsa ndikusonkhanitsa zitsanzo zamagazi mfundo iliyonse yotsatila (miyezi itatu motalikirana) mkati mwa sabata imodzi isanachitike opaleshoni, mwezi umodzi pambuyo pa opaleshoni, ndi chithandizo cha postoperative adjuvant 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; gululi linapezanso kuti kuyesa kophatikizana kwa ctDNA ndi CEA kunawongolera pang'ono kuti azindikire kubwereza (AUC=0.849), koma kusiyana kwake sikunali kwakukulu poyerekeza ndi kuyesa kwa ctDNA (AUC=0.839) kokha Kusiyanaku sikunali kwakukulu poyerekeza ndi ctDNA yokha (AUC= Pa 0.839).
Magawo azachipatala ophatikizidwa ndi ziwopsezo pakali pano ndiye maziko akulu a chiopsezo cha odwala khansa, ndipo m'malingaliro apano, odwala ambiri amabwereranso [4], ndipo pakufunika mwachangu zida zowongolera bwino monga chithandizo chopitilira muyeso komanso. kusalandira chithandizo kumakhalapo m'chipatala. 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 zidawonetsa kuti chiwopsezo chobwereranso chinali chokwera kwambiri kwa odwala omwe ali ndi kuyezetsa kwamphamvu kwa ctDNA kuposa odwala omwe ali ndi ctDNA yoyipa panthawi yowunikiranso matenda pambuyo pa chithandizo chotsimikizika (pambuyo pa opaleshoni yayikulu + chithandizo chamankhwala) (Chithunzi 3ACD), ndi kuti ctDNA imatha kuwonetsa chotupa kuyambiranso mpaka miyezi 20 kale kuposa kujambula (Chithunzi 3B), kupereka mwayi wozindikira matenda msanga. 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 kusintha kwa masinthidwe ndikuti sichifunikira kuwunika kwamtundu wonse wamtundu wa chotupa, imagwiritsidwa ntchito mwachindunji kuyezetsa magazi, ndikupewa zotsatira zabodza chifukwa chozindikira kusintha kwachilengedwe kochokera kuchibadwa. matenda oopsa, matenda oopsa, clonal hematopoiesis.
Kafukufukuyu ndi maphunziro ena okhudzana nawo amatsimikizira kuti kuyezetsa kwa ctDNA-based MRD ndiye chinthu chofunikira kwambiri chodziyimira pawokha pachiwopsezo cha siteji ya I-III ya khansa ya colorectal ndipo ingagwiritsidwe ntchito kuthandizira zisankho za chithandizo, kuphatikiza "kukwera" ndi "kutsitsa" kwa adjuvant therapy. MRD ndiye chinthu chofunikira kwambiri chodziyimira pawokha pachiwopsezo chobwereranso pambuyo pa opareshoni ya gawo I-III khansa ya colorectal.
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
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[2] "Katundu wa matenda a khansa ya m'mimba mwa anthu aku China: kodi zasintha m'zaka zaposachedwa? , Chinese Journal of Epidemiology, Vol. 41, No. 10, Okutobala 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.