Comprehensive Analysis to Identify the Epithelial-Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma.
Comprehensive Analysis to Identify the Epithelial-Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma.
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DOI：
10.3389/fsurg.2021.742443
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发表时间：
2021
影响因子：
1.8
通讯作者：
Guo Q
中科院分区：
文献类型：
--
作者：
Wu G;Yang Y;Zhu Y;Li Y;Zhai Z;An L;Liu M;Zheng Y;Wang Y;Zhou Y;Guo Q
背景：肝细胞癌是一种高度异质性疾病，由于缺乏有效的预后预测模型，其发病率和死亡率较高。目的：构建由上皮-间充质转化(EMT)相关免疫基因组成的风险模型，用于评估预后、免疫渗透状态和化疗敏感性。方法：我们从癌症基因组图谱(TCGA)和国际癌症基因组联合会(ICGC)数据库中获取了肝细胞癌标本的转录组和临床数据。采用Pearson相关分析筛选差异表达的EMT相关免疫基因(DE-EMTri-gene)。随后，引入单变量Cox回归筛选预后基因集，构建基于最小绝对收缩和选择算子惩罚性Cox回归的风险模型。此外，还绘制了受试者工作特征(ROC)曲线，以比较新建立的模型与先前模型的预后价值。并利用生物信息学方法对风险模型与化疗药物的生存概率、免疫特性及疗效的相关性进行了分析。结果：最终筛选出6个DE-EMTri基因构建预后模型。1年、2年和3年的曲线下面积(AUC值)分别为0.773、0.721和0.673。分层生存分析显示低分值组预后优于高分值组。单因素和多因素分析显示，危险比[危险比(HR)5.071，95%CI 3.050，8.432；HR 4.396，95%CI 2.624，7.366；P<；0.001]和分期(HR 2.500，95%CI 1.721，3.632；HR 2.111，95%CI 1.443，3.089；P<；0001)是肝癌的独立预测因素。此外，在高危人群中，巨噬细胞、自然杀伤(NK)细胞和调节性T(Treg)细胞显著丰富。最后，高危评分的患者对顺铂、阿霉素、依托泊苷、吉西他滨和丝裂霉素C可能更敏感。结论：我们建立了一个可靠的基于EMTri基因的预后标志，有望为临床预测提供依据。
Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with the high rates of the morbidity and mortality due to the lack of the effective prognostic model for prediction. Aim: To construct a risk model composed of the epithelial–mesenchymal transition (EMT)-related immune genes for the assessment of the prognosis, immune infiltration status, and chemosensitivity. Methods: We obtained the transcriptome and clinical data of the HCC samples from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) databases. The Pearson correlation analysis was applied to identify the differentially expressed EMT-related immune genes (DE-EMTri-genes). Subsequently, the univariate Cox regression was introduced to screen out the prognostic gene sets and a risk model was constructed based on the least absolute shrinkage and selection operator-penalized Cox regression. Additionally, the receiver operating characteristic (ROC) curves were plotted to compare the prognostic value of the newly established model compared with the previous model. Furthermore, the correlation between the risk model and survival probability, immune characteristic, and efficacy of the chemotherapeutics were analyzed by the bioinformatics methods. Results: Six DE-EMTri-genes were ultimately selected to construct the prognostic model. The area under the curve (AUC) values for 1-, 2-, and 3- year were 0.773, 0.721, and 0.673, respectively. Stratified survival analysis suggested that the prognosis of the low-score group was superior to the high-score group. Moreover, the univariate and multivariate analysis indicated that risk score [hazard ratio (HR) 5.071, 95% CI 3.050, 8.432; HR 4.396, 95% CI 2.624, 7.366; p < 0.001] and stage (HR 2.500, 95% CI 1.721, 3.632; HR 2.111, 95% CI 1.443, 3.089; p < 0.001) served as an independent predictive factors in HCC. In addition, the macrophages, natural killer (NK) cells, and regulatory T (Treg) cells were significantly enriched in the high-risk group. Finally, the patients with the high-risk score might be more sensitive to cisplatin, doxorubicin, etoposide, gemcitabine, and mitomycin C. Conclusion: We established a reliable EMTri-genes-based prognostic signature, which may hold promise for the clinical prediction.
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影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
4.7
作者：
Budhwani M;Mazzieri R;Dolcetti R
通讯作者：
Dolcetti R
影响因子：
9.8
作者：
Altekruse, Sean F.;Henley, S. Jane;Cucinelli, James E.;McGlynn, Katherine A.
通讯作者：
McGlynn, Katherine A.
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影响因子：
5
作者：
Bian S;Ni W;Zhu M;Song Q;Zhang J;Ni R;Zheng W
通讯作者：
Zheng W
美国肝细胞癌的流行病学：我们在哪里？我们去哪里？
影响因子：
13.5
作者：
El-Serag, Hashem B.;Kanwal, Fasiha
通讯作者：
Kanwal, Fasiha