Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer.
Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer.
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NLRP3 炎性体的泛癌分析对人类癌症的预后和免疫治疗具有潜在影响。
DOI：
10.1093/bib/bbaa345
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发表时间：
2021-07-20
影响因子：
9.5
通讯作者：
Zhao L
中科院分区：
文献类型：
--
作者：
Ju M;Bi J;Wei Q;Jiang L;Guan Q;Zhang M;Song X;Chen T;Fan J;Li X;Wei M;Zhao L
NLRP 3炎性小体作为一把双刃剑被引入肿瘤发生中，并通过调节宿主免疫来影响免疫治疗反应。然而，缺乏对人类癌症中NLRP 3炎性小体相关基因的系统评估，并且NLRP 3炎性小体在癌症免疫治疗（CIT）反应中的预测作用仍未探索。因此，在这项研究中，我们对24种人类癌症中的NLRP 3-炎性小体相关基因进行了泛癌症分析。在这24种癌症中，15种癌症在正常和肿瘤样品之间具有显著不同的NLRP 3-炎性小体相关基因表达。考克斯回归分析显示NLRP 3炎性小体评分可作为皮肤黑色素瘤的独立预后因素。进一步分析表明，NLRP 3炎性体可能主要通过介导肿瘤浸润淋巴细胞和巨噬细胞来影响肿瘤免疫，并且NLRP 3炎性体对肿瘤微环境中的肿瘤类型的免疫的影响是不同的。我们还发现，与肿瘤突变负荷（TMB）和糖酵解活性（已被报道为免疫预测因子）相比，NLRP 3炎性小体评分可能是免疫特征的更强预测因子。此外，使用六个CIT反应数据集分析NLRP 3炎性小体与CIT反应之间的关联揭示了NLRP 3炎性小体对不同癌症患者的免疫治疗反应的预测价值。我们的研究说明了NLRP 3炎性小体在多种癌症类型中的特征，并强调了其作为CIT反应的预测生物标志物的潜在价值，这可以为进一步研究NLRP 3炎性小体的预后和治疗潜力铺平道路。
NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (CIT) response remains unexplored. Thus, in this study, we performed a pan-cancer analysis of NLRP3-inflammasome-related genes across 24 human cancers. Out of these 24 cancers, 15 cancers had significantly different expression of NLRP3-inflammasome-related genes between normal and tumor samples. Meanwhile, Cox regression analysis showed that the NLRP3 inflammasome score could be served as an independent prognostic factor in skin cutaneous melanoma. Further analysis indicated that NLRP3 inflammasome may influence tumor immunity mainly by mediating tumor-infiltrating lymphocytes and macrophages, and the effect of NLRP3 inflammasome on immunity is diverse across tumor types in tumor microenvironment. We also found that the NLRP3 inflammasome score could be a stronger predictor for immune signatures compared with tumor mutation burden (TMB) and glycolytic activity, which have been reported as immune predictors. Furthermore, analysis of the association between NLRP3 inflammasome and CIT response using six CIT response datasets revealed the predictive value of NLRP3 inflammasome for immunotherapy response of patients in diverse cancers. Our study illustrates the characterization of NLRP3 inflammasome in multiple cancer types and highlights its potential value as a predictive biomarker of CIT response, which can pave the way for further investigation of the prognostic and therapeutic potentials of NLRP3 inflammasome.
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DOI：
10.1084/jem.20161707
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daley D;Mani VR;Mohan N;Akkad N;Pandian GSDB;Savadkar S;Lee KB;Torres-Hernandez A;Aykut B;Diskin B;Wang W;Farooq MS;Mahmud AI;Werba G;Morales EJ;Lall S;Wadowski BJ;Rubin AG;Berman ME;Narayanan R;Hundeyin M;Miller G
通讯作者：
Miller G
影响因子：
8.7
作者：
Man SM;Kanneganti TD
通讯作者：
Kanneganti TD
DOI：
10.1084/jem.20100050
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen IC;TeKippe EM;Woodford RM;Uronis JM;Holl EK;Rogers AB;Herfarth HH;Jobin C;Ting JP
通讯作者：
Ting JP
DOI：
10.1126/science.aan5951
发表时间：
2018-02-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Miao D;Margolis CA;Gao W;Voss MH;Li W;Martini DJ;Norton C;Bossé D;Wankowicz SM;Cullen D;Horak C;Wind-Rotolo M;Tracy A;Giannakis M;Hodi FS;Drake CG;Ball MW;Allaf ME;Snyder A;Hellmann MD;Ho T;Motzer RJ;Signoretti S;Kaelin WG Jr;Choueiri TK;Van Allen EM
通讯作者：
Van Allen EM
影响因子：
11.1
作者：
Chen, Lih-Chyang;Wang, Li-Jie;Tsang, Nang-Ming;Ojcius, David M.;Chen, Chia-Chun;OuYang, Chun-Nan;Hsueh, Chuen;Liang, Ying;Chang, Kai-Ping;Chen, Chiu-Chin;Chang, Yu-Sun
通讯作者：
Chang, Yu-Sun