Homologous Recombination Related Signatures Predict Prognosis and Immunotherapy Response in Metastatic Urothelial Carcinoma.
Homologous Recombination Related Signatures Predict Prognosis and Immunotherapy Response in Metastatic Urothelial Carcinoma.
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DOI：
10.3389/fgene.2022.875128
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发表时间：
2022
影响因子：
3.7
通讯作者：
Wang, Zhiping
中科院分区：
文献类型：
--
作者：
Li, Pan;Chen, Chaohu;Li, Jianpeng;Yang, Li;Wang, Yuhan;Dong, Zhilong;Mi, Jun;Zhang, Yunxin;Wang, Juan;Wang, Hanzhang;Rodriguez, Ronald;Tian, Junqiang;Wang, Zhiping
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目的：本研究使用同源重组（HR）相关标签开发了一种临床预测模型，用于筛选免疫检查点抑制剂（ICI）的靶细胞群体，并确定晚期转移性尿路上皮癌中的枢纽基因。 研究方法：应用单样本基因富集分析和加权基因共表达网络分析来识别IMvigor 210队列样本中与免疫应答和HR相关的模块。利用主成分分析来确定不同组织亚型和临床变量中HR相关模块基因签名得分的差异。风险预测模型和列线图开发使用差异基因表达分析与HR评分，最小绝对收缩和选择算子，和多变量比例风险模型回归。此外，通过分析HR相关基因对主成分和总生存分析的贡献来确定枢纽基因。最后，分析来自GSE 133624、GSE 13507、TCGA和其他数据集的临床特征，以验证中枢基因与肿瘤生长和突变之间的关系。 结果：完全/部分缓解组HR评分显著高于稳定/进展组。大多数与HR相关的基因被发现参与细胞周期等。基因组不稳定、高肿瘤水平和高免疫水平的样本均表现出比其他样本类别显著更高的HR评分，并且较高的HR评分与ICI治疗后改善的存活率相关。确定了AUNIP、SEPT、FAM 72 D、CAMKV、CXCL 9和FOXN 4的风险评分，训练组和验证组的生存时间明显不同。风险评分、肿瘤新抗原负荷、错配修复和细胞周期调节被发现是免疫治疗后生存时间的独立预测因子。中枢基因（如EME 1、RAD 51 AP 1和RAD 54 L）表达水平高的患者在免疫治疗后存活的机会更大。这些基因在肿瘤、高级别癌症和浸润性癌症中的表达水平显著高于其他类别，并且与TP 53和RB 1突变相关。 结论：HR相关基因在基因组不稳定的样本中上调，可以使用基于HR特征的正态图模型预测用ICI治疗后mUC患者的生存时间。
Objective: This study used homologous recombination (HR) related signatures to develop a clinical prediction model for screening immune checkpoint inhibitors (ICIs) advantaged populations and identify hub genes in advanced metastatic urothelial carcinoma. Methods: The single-sample gene enrichment analysis and weighted gene co-expression network analysis were applied to identify modules associated with immune response and HR in IMvigor210 cohort samples. The principal component analysis was utilized to determine the differences in HR-related module gene signature scores across different tissue subtypes and clinical variables. Risk prediction models and nomograms were developed using differential gene expression analysis associated with HR scores, least absolute shrinkage and selection operator, and multivariate proportional hazards model regression. Additionally, hub genes were identified by analyzing the contribution of HR-related genes to principal components and overall survival analysis. Finally, clinical features from GSE133624, GSE13507, the TCGA, and other data sets were analyzed to validate the relationship between hub genes and tumor growth and mutation. Results: The HR score was significantly higher in the complete/partial response group than in the stable/progressive disease group. The majority of genes associated with HR were discovered to be involved in the cell cycle and others. Genomically unstable, high tumor level, and high immune level samples all exhibited significantly higher HR score than other sample categories, and higher HR scores were related to improved survival following ICIs treatment. The risk scores for AUNIP, SEPT, FAM72D, CAMKV, CXCL9, and FOXN4 were identified, and the training and verification groups had markedly different survival times. The risk score, tumor neoantigen burden, mismatch repair, and cell cycle regulation were discovered to be independent predictors of survival time following immunotherapy. Patients with a high level of expression of hub genes such as EME1, RAD51AP1, and RAD54L had a greater chance of surviving following immunotherapy. These genes are expressed at significantly higher levels in tumors, high-grade cancer, and invasive cancer than other categories, and are associated with TP53 and RB1 mutations. Conclusion: HR-related genes are upregulated in genomically unstable samples, the survival time of mUC patients after treatment with ICIs can be predicted using a normogram model based on HR signature.
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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：
45.3
作者：
Massard, Christophe;Gordon, Michael S.;Segal, Neil H.
通讯作者：
Segal, Neil H.
DOI：
10.1016/j.apsb.2021.01.003
发表时间：
2021-10
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Jiang M;Jia K;Wang L;Li W;Chen B;Liu Y;Wang H;Zhao S;He Y;Zhou C
通讯作者：
Zhou C
影响因子：
11.2
作者：
通讯作者：
--
影响因子：
13.6
作者：
Calzetta NL;González Besteiro MA;Gottifredi V
通讯作者：
Gottifredi V