Identification of an immune-related genes signature to predict risk of recurrence for patients with laryngeal squamous cell carcinoma.

Xiu Hong, Yang Li, Qian Lv, Jun An, Ying Liu, Xiuli Wang, Rui Li, Yuqiang Hu, Bing Liu
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Abstract

Objective: Numerous studies indicate that immune-related genes (IRGs) are closely related to tumorigenesis and tumor progression. We aimed to establish a robust IRGs-based signature to predict risk of recurrence for patients with laryngeal squamous cell carcinoma (LSCC).

Methods: Gene expression profiles were acquired to select differentially expressed IRGs (DEIRGs) between tumor and adjacent normal tissues. Functional enrichment analysis was performed to explore the biological roles of DEIRGs in LSCC. Univariate Cox analyses and LASSO regression model were used to construct a IRGs-based signature with the ability to predict recurrence for LSCC patients.

Results: A total of 272 DEIRGs were identified, of which 20 DEIRGs were significantly associated with recurrence-free survival (RFS). Subsequently, we constructed an eleven-IRGs signature that could classify patients into high-risk or low-risk groups in TCGA-LSCC training cohort. Patients in high-risk groups suffered from shorter RFS (log-rank p = 9.69E-06). Besides, the recurrence rate of high-risk group was significantly higher than that of low-risk group (41.1% vs. 13.7%; Fisher's exact test p < 0.001). The predictive performance was validated in an independent cohort (GSE27020, log-rank p = 1.43E-03). Person correlation analysis showed that the risk scores calculated by eleven-IRGs signature were significantly associated with filtrating immune cells. Furthermore, three immune checkpoint molecules were significantly over-expressed in the high-risk group.

Conclusion: Our findings for the first time constructed a robust IRGs-based signature to precisely predict risk of recurrence and further provided a deeper understanding of IRGs regulatory mechanism in LSCC pathogenesis.

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鉴定免疫相关基因标记以预测喉鳞癌患者复发的风险。
目的:大量研究表明免疫相关基因(IRGs)与肿瘤的发生和发展密切相关。我们的目的是建立一个强大的基于irgs的信号来预测喉鳞状细胞癌(LSCC)患者的复发风险。方法:获取基因表达谱,筛选肿瘤与邻近正常组织间差异表达的IRGs (DEIRGs)。通过功能富集分析探讨DEIRGs在LSCC中的生物学作用。采用单因素Cox分析和LASSO回归模型构建基于irgs的特征,预测LSCC患者的复发。结果:共鉴定出272个DEIRGs,其中20个DEIRGs与无复发生存(RFS)显著相关。随后,我们构建了一个11 - irgs签名,可以将TCGA-LSCC培训队列中的患者分为高风险组或低风险组。高危组患者的RFS较短(log-rank p = 9.69E-06)。高危组复发率明显高于低危组(41.1% vs 13.7%;费雪确切检验p < 0.001)。在独立队列中验证了预测性能(GSE27020, log-rank p = 1.43E-03)。个体相关分析显示,11 - irgs特征计算的风险评分与过滤免疫细胞显著相关。此外,三种免疫检查点分子在高危组中显著过表达。结论:我们的研究结果首次构建了基于IRGs的可靠特征,可以精确预测复发风险,并进一步深入了解IRGs在LSCC发病机制中的调控机制。
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来源期刊
International Journal of Immunopathology and Pharmacology
International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology
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期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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