Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.
Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.
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DOI：
10.1038/s41591-022-01930-z
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发表时间：
2022-08
期刊：
影响因子：
82.9
通讯作者：
Garcia-Aguilar, Julio
中科院分区：
文献类型：
--
作者：
Chatila, Walid K.;Kim, Jin K.;Walch, Henry;Marco, Michael R.;Chen, Chin-Tung;Wu, Fan;Omer, Dana M.;Khalil, Danny N.;Ganesh, Karuna;Qu, Xuan;Luthra, Anisha;Choi, Seo-Hyun;Ho, Yu-Jui;Kundra, Ritika;Groves, Katharine I.;Chow, Oliver S.;Cercek, Andrea;Weiser, Martin R.;Widmar, Maria;Wei, Iris H.;Pappou, Emmanouil P.;Nash, Garrett M.;Paty, Philip B.;Shi, Qian;Vakiani, Efsevia;Duygu Selcuklu, S.;Donoghue, Mark T. A.;Solit, David B.;Berger, Michael F.;Shia, Jinru;Pelossof, Raphael;Romesser, Paul B.;Yaeger, Rona;Smith, J. Joshua;Schultz, Nikolaus;Sanchez-Vega, Francisco;Garcia-Aguilar, Julio
直肠癌的发病率在50岁以下的患者中正在增加。局部晚期直肠癌仍采用新辅助放疗、化疗和手术治疗，但最近的证据表明，完全缓解的患者可以永久避免手术。为了确定新辅助治疗反应的相关性，我们分析了738例未经治疗的直肠癌的基因组和转录组学特征。APC突变在低位直肠的发生率低于中、高位直肠，这可以解释远端肿瘤更具侵袭性的行为。在治疗不可知的方式中，没有体细胞改变与新辅助治疗的反应显着相关，但KRAS突变与接受新辅助放化疗后巩固化疗的患者的更快复发相关。IGF 2和L1 CAM的过度表达与新辅助治疗的应答降低相关。免疫浸润的RNA-Seq估计确定了一个微卫星稳定的免疫热肿瘤子集，其反应增加，无病生存期延长。
The incidence of rectal cancer is increasing among patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations showed significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy. RNA-Seq estimates of immune infiltration identified a subset of microsatellite stable immune hot tumors with increased response and prolonged disease-free survival.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
3.2
作者：
Cheng, Lv-Jia;Chen, Jian-Hui;Chen, Chuang-Qi
通讯作者：
Chen, Chuang-Qi
影响因子：
50.3
作者：
Bielski CM;Donoghue MTA;Gadiya M;Hanrahan AJ;Won HH;Chang MT;Jonsson P;Penson AV;Gorelick A;Harris C;Schram AM;Syed A;Zehir A;Chapman PB;Hyman DM;Solit DB;Shannon K;Chandarlapaty S;Berger MF;Taylor BS
通讯作者：
Taylor BS
影响因子：
3.7
作者：
Chow OS;Kuk D;Keskin M;Smith JJ;Camacho N;Pelossof R;Chen CT;Chen Z;Avila K;Weiser MR;Berger MF;Patil S;Bergsland E;Garcia-Aguilar J
通讯作者：
Garcia-Aguilar J
影响因子：
9
作者：
Garcia-Aguilar J;Chen Z;Smith DD;Li W;Madoff RD;Cataldo P;Marcet J;Pastor C
通讯作者：
Pastor C