基于肿瘤微环境的头颈部鳞状细胞癌细胞成分相关预后特征

Siyu Li, Yajun Gu, Junguo Wang, Dengbin Ma, Xiaoyun Qian, Xia Gao
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摘要

头颈部鳞状细胞癌(HNSCC)是一种高死亡率的异质性疾病。肿瘤微环境(tumor microenvironment, TME)是由许多非癌细胞组成的,它们有助于肿瘤的发生和预测治疗效果。在这项研究中,我们旨在建立一个基于TME的细胞成分相关的预后模型。我们使用xCell算法从癌症基因组图谱(TCGA) HNSCC队列样本中筛选细胞成分富集。采用单因素Cox和多因素Cox回归分析,建立最优独立风险模型。使用Gene Expression Omnibus数据集进一步验证该模型的预后价值。我们发现低风险组的患者有更好的结果和激活免疫,并且可能从免疫检查点抑制剂治疗中获益更多。我们还探索了可能调节这些已鉴定细胞成分的microrna (miRNA),并发现11种miRNA的表达水平影响总体存活时间。此外,它们的靶mrna在TCGA队列中存在差异表达,并在细胞周期途径、细胞外基质受体相互作用、人乳头瘤病毒感染和癌症途径中富集。总之,我们的细胞成分相关标记是一个有希望的预后生物标志物,为TME中非肿瘤成分的预测价值提供了新的见解。
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A Cell Component-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma Based on the Tumor Microenvironment

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with a high mortality rate. The tumor microenvironment (TME) is composed of numerous noncancerous cells that contribute to tumorigenesis and prediction of therapeutic effects. In this study, we aimed to develop a cell component-related prognostic model based on TME. We screened cell component enrichments from samples in The Cancer Genome Atlas (TCGA) HNSCC cohort using the xCell algorithm. Univariate Cox and multivariate Cox regression analyses were performed to establish an optimal independent risk model. The prognostic value of the model was further validated using Gene Expression Omnibus datasets. We found that patients in the low-risk group had a better outcome and activated immunity and may benefit more from the immune checkpoint inhibitor therapy. We also explored microRNAs (miRNAs) that may regulate these identified cell components, and 11 miRNA expression levels influenced the overall survival time. Moreover, their target mRNAs were differentially expressed in TCGA cohort and enriched in pathways of cell cycle pathways, extracellular matrix receptor interaction, human papillomavirus infection, and cancer. In summary, our cell component-related signature was a promising prognostic biomarker that provides new insights into the predictive value of nontumor components in the TME.

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Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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