A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer.
A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer.
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DOI：
10.1038/s41698-021-00172-5
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发表时间：
2021-05-04
影响因子：
7.9
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Jiao X;Wei X;Li S;Liu C;Chen H;Gong J;Li J;Zhang X;Wang X;Peng Z;Qi C;Wang Z;Wang Y;Wang Y;Zhuo N;Zhang H;Lu Z;Shen L
遗传变异与免疫治疗益处之间的关联已得到广泛认可，但胃肠道癌症的此类证据仍然有限。我们分析了来自纪念斯隆凯特琳 (MSK) 癌症中心队列的 227 名免疫治疗胃肠道癌症患者的基因组图谱。使用 LASSO Cox 回归构建胃肠道免疫预后特征 (GIPS)。根据这一特征，患者被分为两个具有不同预后的亚组（p<<0.001）。 GIPS 的预后价值在 Janjigian 和 Pender 队列 (N = 54) 和北京大学肿瘤医院队列 (N = 92) 中得到了一致验证。多变量分析表明，GIPS 是一个独立的预后生物标志物。值得注意的是，GIPS 高的肿瘤表明 T 细胞炎症表型和免疫激活。研究结果表明，GIPS 是胃肠道癌症免疫治疗生存的有力预测因子，并可能作为指导免疫治疗决策的潜在生物标志物。
The association between genetic variations and immunotherapy benefit has been widely recognized, while such evidence in gastrointestinal cancer remains limited. We analyzed the genomic profile of 227 immunotherapeutic gastrointestinal cancer patients treated with immunotherapy, from the Memorial Sloan Kettering (MSK) Cancer Center cohort. A gastrointestinal immune prognostic signature (GIPS) was constructed using LASSO Cox regression. Based on this signature, patients were classified into two subgroups with distinctive prognoses (p < 0.001). The prognostic value of the GIPS was consistently validated in the Janjigian and Pender cohort (N = 54) and Peking University Cancer Hospital cohort (N = 92). Multivariate analysis revealed that the GIPS was an independent prognostic biomarker. Notably, the GIPS-high tumor was indicative of a T-cell-inflamed phenotype and immune activation. The findings demonstrated that GIPS was a powerful predictor of immunotherapeutic survival in gastrointestinal cancer and may serve as a potential biomarker guiding immunotherapy treatment decisions.
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影响因子：
28.2
作者：
Grasso CS;Giannakis M;Wells DK;Hamada T;Mu XJ;Quist M;Nowak JA;Nishihara R;Qian ZR;Inamura K;Morikawa T;Nosho K;Abril-Rodriguez G;Connolly C;Escuin-Ordinas H;Geybels MS;Grady WM;Hsu L;Hu-Lieskovan S;Huyghe JR;Kim YJ;Krystofinski P;Leiserson MDM;Montoya DJ;Nadel BB;Pellegrini M;Pritchard CC;Puig-Saus C;Quist EH;Raphael BJ;Salipante SJ;Shin DS;Shinbrot E;Shirts B;Shukla S;Stanford JL;Sun W;Tsoi J;Upfill-Brown A;Wheeler DA;Wu CJ;Yu M;Zaidi SH;Zaretsky JM;Gabriel SB;Lander ES;Garraway LA;Hudson TJ;Fuchs CS;Ribas A;Ogino S;Peters U
通讯作者：
Peters U
影响因子：
45.3
作者：
Doi, Toshihiko;Piha-Paul, Sarina A.;Bennouna, Jaafar
通讯作者：
Bennouna, Jaafar
影响因子：
7.3
作者：
Cho J;Chang YH;Heo YJ;Kim S;Kim NK;Park JO;Kang WK;Lee J;Kim KM
通讯作者：
Kim KM
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
影响因子：
11.5
作者：
Dong, Zhong-Yi;Zhong, Wen-Zhao;Wu, Yi-Long
通讯作者：
Wu, Yi-Long