Clinically conserved genomic subtypes of gastric adenocarcinoma.
Clinically conserved genomic subtypes of gastric adenocarcinoma.
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DOI：
10.1186/s12943-023-01796-w
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发表时间：
2023-09-06
期刊：
影响因子：
37.3
通讯作者：
Lee, Ju-Seog
中科院分区：
文献类型：
--
作者：
Jeong, Yun Seong;Eun, Young-Gyu;Lee, Sung Hwan;Kang, Sang-Hee;Yim, Sun Young;Kim, Eui Hyun;Noh, Joo Kyung;Sohn, Bo Hwa;Woo, Seon Rang;Kong, Moonkyoo;Nam, Deok Hwa;Jang, Hee-Jin;Lee, Hyun-Sung;Song, Shumei;Oh, Sang Cheul;Lee, Jeeyun;Ajani, Jaffer A.;Lee, Ju-Seog
关键词：
胃腺癌（GAC）是一种具有基因组异质性和临床异质性的致死性疾病。通过整合8个先前建立的GAC亚型的基因组特征，我们鉴定了6个临床和分子上不同的基因组共有亚型（CGS）。CGS 1具有最差的预后、非常高的干细胞特征和高IGF 1表达，但低基因组改变。CGS 2富含典型上皮基因表达。CGS 3和CGS 4具有高拷贝数改变和低免疫反应性。然而，CGS 3和CGS 4的不同之处在于CGS 3具有高HER 2活化，而CGS 4具有高SALL 4和KRAS活化。CGS 5具有高突变负荷和适度高的免疫反应性，这是微卫星不稳定肿瘤的特征。大多数CGS 6肿瘤对爱泼斯坦巴尔病毒呈阳性，并显示极高水平的甲基化和高免疫反应性。在对基因组和蛋白质组数据的系统分析中，我们估计了每个共有亚型对标准和实验治疗（如放射治疗，靶向治疗和免疫治疗）的潜在反应率。有趣的是，CGS 3由于其高基础水平的铁凋亡而与放化疗治疗的益处显著相关。此外，我们还确定了每个共有亚型的潜在治疗靶点。因此，共有亚型产生了稳健的分类，并为基于亚型的定制干预提供了额外的表征。在线版本包含补充材料，可通过10.1186/s12943-023-01796-w获得。
Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions. The online version contains supplementary material available at 10.1186/s12943-023-01796-w.
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影响因子：
15.8
作者：
Kim JH;Sohn BH;Lee HS;Kim SB;Yoo JE;Park YY;Jeong W;Lee SS;Park ES;Kaseb A;Kim BH;Kim WB;Yeon JE;Byun KS;Chu IS;Kim SS;Wang XW;Thorgeirsson SS;Luk JM;Kang KJ;Heo J;Park YN;Lee JS
通讯作者：
Lee JS
影响因子：
51.1
作者：
Cats, Annemieke;Jansen, Edwin P. M.;Verheij, Marcel
通讯作者：
Verheij, Marcel
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
51.1
作者：
Cheong, Jae-Ho;Yang, Han-Kwang;Noh, Sung Hoon
通讯作者：
Noh, Sung Hoon
一线Nivolumab加化学疗法与化学疗法仅用于晚期胃，胃食管结和食管腺癌（Checkmate 649）：一项随机，开放标签，第3阶段试验。
DOI：
10.1016/s0140-6736(21)00797-2
发表时间：
2021-07-03
期刊：
Lancet (London, England)
影响因子：
--
作者：
Janjigian YY;Shitara K;Moehler M;Garrido M;Salman P;Shen L;Wyrwicz L;Yamaguchi K;Skoczylas T;Campos Bragagnoli A;Liu T;Schenker M;Yanez P;Tehfe M;Kowalyszyn R;Karamouzis MV;Bruges R;Zander T;Pazo-Cid R;Hitre E;Feeney K;Cleary JM;Poulart V;Cullen D;Lei M;Xiao H;Kondo K;Li M;Ajani JA
通讯作者：
Ajani JA