Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma.
Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma.
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ADME 相关基因特征的开发和验证，用于头颈鳞状细胞癌的生存、治疗结果和免疫细胞浸润
DOI：
10.3389/fimmu.2022.905635
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wen, Xin
中科院分区：
文献类型：
--
作者：
Tang, Xinran;Li, Rui;Wu, Dehua;Wang, Yikai;Zhao, Fang;Lv, Ruxue;Wen, Xin
关键词：
ADME基因是一组参与药物吸收、分配、代谢和排泄的基因。然而，ADME基因在头颈部鳞状细胞癌(HNSCC)中的预后价值和功能仍很不清楚。在这项研究中，我们在癌症基因组图谱(TCGA)训练队列中通过最小绝对收缩和选择算子(LASSO)分析建立了与ADME相关的预后模型，并通过TCGA内部验证队列和基因表达总表(GEO)外部队列验证了该模型的稳健性。14个基因标记将患者分为高风险组或低风险组。高危评分的患者的总体生存率(OS)和无病生存率(DFS)显著低于低危评分的患者。使用受试者工作特征(ROC)曲线分析来确认该签名对OS和DFS的预测效果。此外，基因本体论(GO)和京都基因与基因组百科全书(KEGG)的途径分析表明，免疫相关功能和途径得到了丰富，如淋巴细胞激活、白细胞细胞-细胞黏附和T辅助细胞分化。通过估计RNA转录本的相对亚群(Ciberort)和其他分析进行的细胞类型鉴定显示，免疫细胞(尤其是B细胞和T细胞)在低风险组的渗透水平明显较高。此外，低风险评分的患者与免疫治疗和化疗受益显著相关。总之，我们构建了一个新的ADME相关预后和治疗生物标记物，与HNSCC患者的免疫细胞浸润相关。
ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic model through the least absolute shrinkage and selection operator (LASSO) analysis in the Cancer Genome Atla (TCGA) training cohort and its robustness was validated by TCGA internal validation cohort and a Gene Expression Omnibus (GEO) external cohort. The 14-gene signature stratified patients into high- or low-risk groups. Patients with high-risk scores exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than those with low-risk scores. Receiver operating characteristic (ROC) curve analysis was used to confirm the signature’s predictive efficacy for OS and DFS. Furthermore, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses showed that immune-related functions and pathways were enriched, such as lymphocyte activation, leukocyte cell-cell adhesion and T-helper cell differentiation. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and other analyses revealed that immune cell (especially B cell and T cell) infiltration levels were significantly higher in the low-risk group. Moreover, patients with low-risk scores were significantly associated with immunotherapy and chemotherapy treatment benefit. In conclusion, we constructed a novel ADME-related prognostic and therapeutic biomarker associated with immune cell infiltration of HNSCC patients.
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影响因子：
5.2
作者：
Hu DG;Mackenzie PI;Nair PC;McKinnon RA;Meech R
通讯作者：
Meech R
影响因子：
2.1
作者：
Dempsey, Jacqueline M.;Kidwell, Kelley M.;Hertz, Daniel L.
通讯作者：
Hertz, Daniel L.
DOI：
10.1124/jpet.118.255018
发表时间：
2019-03-01
影响因子：
3.5
作者：
Hu, Dong Gui;Marri, Shashikanth;Meech, Robyn
通讯作者：
Meech, Robyn
影响因子：
2.4
作者：
Han, Jiming;Wang, Lu;Zhang, Jing
通讯作者：
Zhang, Jing
影响因子：
3.5
作者：
Jittikoon, Jiraphun;Mahasirimongkol, Surakameth;Chantratita, Wasun
通讯作者：
Chantratita, Wasun