Mutated genes on ctDNA detecting postoperative recurrence presented reduced neoantigens in primary tumors in colorectal cancer cases.
Mutated genes on ctDNA detecting postoperative recurrence presented reduced neoantigens in primary tumors in colorectal cancer cases.
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DOI：
10.1038/s41598-023-28575-3
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发表时间：
2023-01-24
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
突变ctDNA的检测和测序是结直肠癌术后处理中不可替代的临床手段之一。然而，我们很想了解突变基因的基本特征，这些突变基因包括原发部位的整个突变基因中的转移部位。在目前的回顾研究中，我们使用47个血浆样本对ctDNA进行了靶向重测序，并建立了一个携带原发和复发肿瘤之间常见突变基因的癌症小组。我们发现，ctDNA中的突变基因表现出免疫抵抗特征，表现为原发肿瘤中由于丧失表达或与HLA结合而导致呈递新抗原的能力受损。与所有原发肿瘤突变基因的预测新抗原相比，该板上常见突变基因的新抗原肽有丰富的表达，但不与人类白细胞抗原结合。因此，可以在术后频繁检测ctDNA突变以确定复发；然而，这些突变的基因来自免疫耐受克隆，因为在原发结直肠癌肿瘤中失去了新的抗原提呈。
The detection and sequencing of the mutated ctDNA is one of the irreplaceable clinical measures in the postoperative management of colorectal cancer (CRC) cases. However, we are curious to comprehend the essential traits of mutated genes comprising metastatic sites out of whole mutated genes in primary sites. In the current retrospective study, we conducted target resequencing of ctDNA using 47 plasma samples and established a cancer panel carrying the commonly mutated genes between primary and recurrent tumors. We found that mutated genes in ctDNA indicated immune-resistance traits with respect to the impaired ability to present neoantigens by loss of expression or binding affinity to HLA in the primary tumor. Compared with the estimated neoantigens from all mutated genes in primary tumors, the neoantigen peptides from commonly mutated genes on the panel showed abundant expression but no binding affinity to HLA. Therefore, ctDNA mutations can be frequently and postoperatively detected to identify recurrence; however, these mutated genes were derived from immune-tolerated clones owing to the loss of neoantigen presentation in primary CRC tumors.
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影响因子：
28.2
作者：
Pectasides E;Stachler MD;Derks S;Liu Y;Maron S;Islam M;Alpert L;Kwak H;Kindler H;Polite B;Sharma MR;Allen K;O'Day E;Lomnicki S;Maranto M;Kanteti R;Fitzpatrick C;Weber C;Setia N;Xiao SY;Hart J;Nagy RJ;Kim KM;Choi MG;Min BH;Nason KS;O'Keefe L;Watanabe M;Baba H;Lanman R;Agoston AT;Oh DJ;Dunford A;Thorner AR;Ducar MD;Wollison BM;Coleman HA;Ji Y;Posner MC;Roggin K;Turaga K;Chang P;Hogarth K;Siddiqui U;Gelrud A;Ha G;Freeman SS;Rhoades J;Reed S;Gydush G;Rotem D;Davison J;Imamura Y;Adalsteinsson V;Lee J;Bass AJ;Catenacci DV
通讯作者：
Catenacci DV
影响因子：
16.6
作者：
Chabon JJ;Simmons AD;Lovejoy AF;Esfahani MS;Newman AM;Haringsma HJ;Kurtz DM;Stehr H;Scherer F;Karlovich CA;Harding TC;Durkin KA;Otterson GA;Purcell WT;Camidge DR;Goldman JW;Sequist LV;Piotrowska Z;Wakelee HA;Neal JW;Alizadeh AA;Diehn M
通讯作者：
Diehn M
使用微滴式数字 PCR 检测肝细胞癌患者的循环肿瘤 DNA 是可行的，并反映了瘤内异质性
影响因子：
3.9
作者：
Huang A;Zhang X;Zhou SL;Cao Y;Huang XW;Fan J;Yang XR;Zhou J
通讯作者：
Zhou J
循环肿瘤 DNA 甲基化谱可实现结直肠癌的早期诊断、预后预测和筛查
影响因子：
17.1
作者：
Luo, Huiyan;Zhao, Qi;Xu, Rui-hua
通讯作者：
Xu, Rui-hua
影响因子：
16.6
作者：
Saito T;Niida A;Uchi R;Hirata H;Komatsu H;Sakimura S;Hayashi S;Nambara S;Kuroda Y;Ito S;Eguchi H;Masuda T;Sugimachi K;Tobo T;Nishida H;Daa T;Chiba K;Shiraishi Y;Yoshizato T;Kodama M;Okimoto T;Mizukami K;Ogawa R;Okamoto K;Shuto M;Fukuda K;Matsui Y;Shimamura T;Hasegawa T;Doki Y;Nagayama S;Yamada K;Kato M;Shibata T;Mori M;Aburatani H;Murakami K;Suzuki Y;Ogawa S;Miyano S;Mimori K
通讯作者：
Mimori K