Clinical Significance and Inflammatory Landscape of aNovel Recurrence-Associated Immune Signature in Stage II/III Colorectal Cancer.
Clinical Significance and Inflammatory Landscape of aNovel Recurrence-Associated Immune Signature in Stage II/III Colorectal Cancer.
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DOI：
10.3389/fimmu.2021.702594
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发表时间：
2021
影响因子：
7.3
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Liu Z;Lu T;Li J;Wang L;Xu K;Dang Q;Liu L;Guo C;Jiao D;Sun Z;Han X
相当多的II/III期结直肠癌（CRC）患者在手术后5年内会复发，这是早期CRC死亡的主要原因。目前的TNM分期系统是有限的，由于异质性的临床结果显示在同一阶段的患者。因此，寻找一种新的工具来识别高复发风险的患者，以改善术后个体化管理是迫切需要的。使用四个独立的公共队列和来自66个组织的qRT-PCR数据，我们开发并验证了基于全局免疫基因的复发相关免疫特征（RAIS）。RAIS的临床和分子特征，肿瘤免疫微环境景观和免疫检查点的配置文件进行了研究。在5个独立的队列中，该评分系统被证明是一个独立的复发因素，并显示出良好的区分度和校准预测1~5年的复发风险。进一步分析发现，高危组TP 53突变率高，而低危组活化的CD 4 +/CD 8 + T细胞和PD-1/PD-L1表达高。RAIS模型对II/III期CRC患者的复发具有高度预测性，这可能成为进一步优化辅助化疗和免疫治疗决策以及为个体患者定制监测方案的有力工具。
A considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need. Using four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated. In five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1. The RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.
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影响因子：
4.6
作者：
Allen WL;Dunne PD;McDade S;Scanlon E;Loughrey M;Coleman H;McCann C;McLaughlin K;Nemeth Z;Syed N;Jithesh P;Arthur K;Wilson R;Coyle V;McArt D;Murray GI;Samuel L;Nuciforo P;Jimenez J;Argiles G;Dienstmann R;Tabernero J;Messerini L;Nobili S;Mini E;Sheahan K;Ryan E;Johnston PG;Van Schaeybroeck S;Lawler M;Longley DB
通讯作者：
Longley DB
影响因子：
4.4
作者：
Corvaisier, M;Moreau-Aubry, A;Jotereau, F
通讯作者：
Jotereau, F
影响因子：
7.4
作者：
Liu Z;Zhang Y;Shi C;Zhou X;Xu K;Jiao D;Sun Z;Han X
通讯作者：
Han X
影响因子：
17.1
作者：
Mlecnik, Bernhard;Bindea, Gabriela;Galon, Jerome
通讯作者：
Galon, Jerome
影响因子：
6.6
作者：
Kim, Seon-Kyu;Kim, Seon-Young;Kim, Jin Cheon
通讯作者：
Kim, Jin Cheon