An immune indicator based on BTK and DPEP2 identifies hot and cold tumors and clinical treatment outcomes in lung adenocarcinoma.
An immune indicator based on BTK and DPEP2 identifies hot and cold tumors and clinical treatment outcomes in lung adenocarcinoma.
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DOI：
10.1038/s41598-023-32276-2
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发表时间：
2023-03-29
影响因子：
4.6
通讯作者：
Hu, Dong
中科院分区：
文献类型：
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作者：
Han, Tao;Liu, Yafeng;Wu, Jing;Bai, Ying;Zhou, Jiawei;Hu, Chunxiao;Zhang, Wenting;Guo, Jianqiang;Wang, Qingsen;Hu, Dong
在肺腺癌（LUAD）中，热肿瘤和冷肿瘤的免疫异质性已被认为是影响免疫治疗和其他常用治疗的主要因素之一。然而，目前仍缺乏能够有效识别冷、热肿瘤免疫表型的生物标志物。首先，通过文献挖掘获得免疫特征，包括巨噬细胞/单核细胞、IFN-γ反应、TGF-β反应、il - 12反应、淋巴细胞活化和ECM/Dve/免疫反应。随后，根据这些免疫特征将LUAD患者进一步聚类为不同的免疫表型。接下来，通过WGCNA分析、单因素分析和lasso-cox分析筛选与免疫表型相关的关键基因，并通过关键基因建立风险特征。此外，我们比较了LUAD高危组和低危组患者的临床病理特征、药物敏感性、免疫浸润丰度、免疫治疗和常用治疗的疗效。将LUAD患者分为免疫热表型组和免疫冷表型组。临床表现显示，与免疫冷表型患者相比，免疫热表型患者具有更高的免疫活性（包括更高的MHC、CYT、免疫、基质、ESTIMATE评分、更高的免疫细胞浸润丰度、更高的TIL丰度和免疫富集亚型的富集）和更好的生存结局。随后，WGCNA分析、单变量分析和lasso-cox分析确定了与免疫表型高度相关的基因：BTK和DPEP2。由BTK和DPEP2组成的风险标志与免疫表型高度相关。高危评分在免疫冷表型患者中富集，低危评分在免疫热表型患者中富集。与高危组相比，低危组临床表现更好，药物敏感性更高，免疫活性程度更高，接受免疫治疗和常用辅助治疗的疗效更好。本研究基于肿瘤微环境冷热免疫表型的异质性，开发了由BTK和DPEP2组成的免疫指标。该指标在预测预后及评价免疫治疗、化疗、放疗疗效方面均有较好的疗效。它有可能在未来促进LUAD的个性化和精确治疗。
In lung adenocarcinoma (LUAD), immune heterogeneity of hot and cold tumors has been recognized as one of the major factors affecting immunotherapy and other common treatments. However, there is still a lack of biomarkers that can effectively identify the immunophenotype of cold and hot tumors. First, the immune signatures were obtained based on literature mining, including macrophage/monocyte, IFN-γ response, TGF-β response, IL12 response, lymphocyte activation, and ECM/Dve/immune response. Subsequently, LUAD patients were further clustered into different immune phenotypes based on these immune signatures. Next, the key genes related to the immune phenotypes were screened by WGCNA analysis, univariate analysis, and lasso-cox analysis, and the risk signature was established via the key genes. In additional, we compared the clinicopathological characteristics, drug sensitivity, the abundance of immune infiltration, and the efficacy of immunotherapy and commonly used therapies between patients in the high- and low-risk groups in LUAD. LUAD patients were divided into immune hot phenotype and immune cold phenotype groups. The clinical presentation showed that patients with the immune hot phenotype had higher immunoactivity (including higher MHC, CYT, immune, stromal, ESTIMATE scores, higher abundance of immune cell infiltration, higher abundance of TIL, and enrichment of immune-enriched subtypes) and better survival outcomes than those with the immune cold phenotype. Subsequently, WGCNA analysis, univariate analysis, and lasso-cox analysis identified the genes highly associated with the immune phenotype: BTK and DPEP2. The risk signature, consisting of BTK and DPEP2, is highly correlated with the immune phenotype. High-risk scores were enriched in patients with immune cold phenotype and low-risk scores were enriched in patients with immune hot phenotype. Compared to the high-risk group, the low-risk group had better clinical performance, higher drug sensitivity, and a higher degree of immunoactivity, as well as better efficacy in receiving immunotherapy and common adjuvant therapy. This study developed an immune indicator consisting of BTK and DPEP2 based on the heterogeneity of hot and cold Immunophenotypes of the tumor microenvironment. This indicator has good efficacy in predicting prognosis and assessing the efficacy of immunotherapy, chemotherapy, and radiotherapy. It has the potential to facilitate personalized and precise treatment of LUAD in the future.
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DOI：
10.1158/1078-0432.ccr-08-1283
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beck AH;Espinosa I;Edris B;Li R;Montgomery K;Zhu S;Varma S;Marinelli RJ;van de Rijn M;West RB
通讯作者：
West RB
影响因子：
50.3
作者：
Jardim DL;Goodman A;de Melo Gagliato D;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
20.3
作者：
He, Xin;Feng, Zijie;Hua, Xianxin
通讯作者：
Hua, Xianxin
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
4.7
作者：
通讯作者：
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