A Prognostic Signature Based on Immunogenomic Profiling Offers Guidance for Esophageal Squamous Cell Cancer Treatment.
A Prognostic Signature Based on Immunogenomic Profiling Offers Guidance for Esophageal Squamous Cell Cancer Treatment.
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基于免疫基因组学分析的预后标记为食管鳞状细胞癌治疗提供指导。
DOI：
10.3389/fonc.2021.603634
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发表时间：
2021
影响因子：
4.7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Gao J;Tang T;Zhang B;Li G
我们的研究旨在开发一种免疫预后特征，为食管鳞状细胞癌（ESCC）的治疗提供准确的指导。通过实施单样本基因组富集分析（ssGSEA），我们基于29个免疫特征的免疫基因组图谱在GSE53625中建立了两个ESCC亚型（免疫高和免疫低）。我们在 TCGA 数据库中验证了这一分类的可靠性和可重复性。由于免疫检查点（包括 PD1、PDL1、CTLA4 和 CD80）的表达较高，免疫力高的患者对免疫疗法的反应最佳。我们利用WGCNA分析来探索免疫高分组的潜在调控机制。我们进一步确定了 GSE53625 中差异表达的免疫相关基因（CCR5、TSPAN2），并构建了独立的双基因预后特征，通过校准图进行了内部验证。我们发现，高危 ESCC 患者的总生存率较低（P=0.002，HR=2.03）。此外，高危ESCC患者的浸润滤泡辅助T细胞、幼稚B细胞和巨噬细胞水平升高，一些免疫检查点（包括B3H7、CTLA4、CD83、OX40L和GEM）水平过表达。此外，通过分析癌症药物敏感性基因组学（GDSC）数据库，高危组对紫杉醇、吉非替尼、厄洛替尼和拉帕替尼等一些化疗药物和靶向药物表现出耐药性。此外，我们还建立了一个稳健的提名图模型来预测 ESCC 患者的临床结局。总之，我们提出的免疫预后特征是一种具有临床潜力的生物标志物，将有助于评估 ESCC 的预后并促进个性化治疗。
Our study aimed to develop an immune prognostic signature that could provide accurate guidance for the treatment of esophageal squamous cell cancer (ESCC). By implementing Single-Sample Gene Set Enrichment Analysis (ssGSEA), we established two ESCC subtypes (Immunity High and Immunity Low) in GSE53625 based on immune-genomic profiling of twenty-nine immune signature. We verified the reliability and reproducibility of this classification in the TCGA database. Immunity High could respond optimally to immunotherapy due to higher expression of immune checkpoints, including PD1, PDL1, CTLA4, and CD80. We used WGCNA analysis to explore the underlying regulatory mechanism of the Immunity High group. We further identified differentially expressed immune-related genes (CCR5, TSPAN2) in GSE53625 and constructed an independent two-gene prognostic signature we internally validated through calibration plots. We established that high-risk ESCC patients had worse overall survival (P=0.002, HR=2.03). Besides, high-risk ESCC patients had elevated levels of infiltrating follicle-helper T cells, naïve B cells, and macrophages as well as had overexpressed levels of some immune checkpoints, including B3H7, CTLA4, CD83, OX40L, and GEM. Moreover, through analyzing the Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk group demonstrated drug resistance to some chemotherapy and targeted drugs such as paclitaxel, gefitinib, erlotinib, and lapatinib. Furthermore, we established a robust nomogram model to predict the clinical outcome in ESCC patients. Altogether, our proposed immune prognostic signature constitutes a clinically potential biomarker that will aid in evaluating ESCC outcomes and promote personalized treatment.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Aldinucci, Donatella;Lorenzon, Debora;Colombatti, Alfonso
通讯作者：
Colombatti, Alfonso
影响因子：
4.7
作者：
Lin Y;Totsuka Y;He Y;Kikuchi S;Qiao Y;Ueda J;Wei W;Inoue M;Tanaka H
通讯作者：
Tanaka H
DOI：
10.1093/jnci/djn211
发表时间：
2008-08-20
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Brown LM;Devesa SS;Chow WH
通讯作者：
Chow WH