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自噬相关标志物预测头颈部鳞状细胞癌。

Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma.

机构信息

Department of Otolaryngology Head and Neck Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Dis Markers. 2020 Oct 19;2020:8899337. doi: 10.1155/2020/8899337. eCollection 2020.

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in the world, with low survival and poor quality of life. Autophagy-associated genes (ATGs) have been reported to be involved in the initiation and progression of malignancies. Here, we aimed to investigate the association between autophagy-associated genes and the outcomes in HNSCC patients.

METHODS

We obtained ATGs with prognostic values by analyzing the datasets from The Cancer Genome Atlas (TCGA) and Human Autophagy Database (HADb). The enrichment functions of autophagy differential genes were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Kaplan-Meier method was applied to the survival curve analysis. A prognostic autophagy-related gene signature was established, and its independence was verified.

RESULTS

We acquired a total of 529 samples and 232 ATGs; further, we identified 45 genes associated with prognosis and built a prognosis autophagy signature based on risk score of 15 genes. Patients were divided into two groups based on risk scores. The Kaplan-Meier curve illustrated that the survival rate of the high-risk group was significantly lower than that of the low-risk group in both the training group and validation group. The ROC curve revealed that the risk score had the highest AUC value in the 3rd and 5th years, reaching 0.703 and 0.724, which are higher than other risk factors such as gender, age, and TNM stage. The nomogram further confirmed its weight in the prognosis of HNSCC patients. Through KEGG and GO enrichment analyses, we observed that ATGs were involved in the tumorigenesis and invasion of tumor by various mediating pathways. We gained 3 hub genes (, , and ) and further analyzed the survival curves, mutations, differential expressions, and their roles in tumors on the online websites.

CONCLUSION

We identified a novel autophagy-related signature that may provide promising biomarker genes for the treatment and prognosis of HNSCC. We need to validate its prognostic value by applying it to the clinic.

摘要

背景

头颈部鳞状细胞癌(HNSCC)是世界上最常见的恶性肿瘤之一,其生存率低,生活质量差。自噬相关基因(ATGs)已被报道参与恶性肿瘤的发生和发展。在这里,我们旨在研究自噬相关基因与 HNSCC 患者结局之间的关系。

方法

我们通过分析来自癌症基因组图谱(TCGA)和人类自噬数据库(HADb)的数据集获得具有预后价值的 ATGs。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析自噬差异基因的富集功能。应用 Kaplan-Meier 法进行生存曲线分析。建立预后相关的自噬基因特征,并验证其独立性。

结果

我们共获得 529 例样本和 232 个 ATGs;进一步确定了与预后相关的 45 个基因,并基于 15 个基因的风险评分构建了预后自噬特征。根据风险评分将患者分为两组。Kaplan-Meier 曲线表明,在训练组和验证组中,高风险组的生存率明显低于低风险组。ROC 曲线表明,风险评分在第 3 年和第 5 年的 AUC 值最高,分别达到 0.703 和 0.724,高于性别、年龄和 TNM 分期等其他危险因素。列线图进一步证实了其在 HNSCC 患者预后中的权重。通过 KEGG 和 GO 富集分析,我们观察到 ATGs 参与了肿瘤的发生和侵袭,通过各种介导途径。我们获得了 3 个枢纽基因(、和),并进一步分析了在线网站上的生存曲线、突变、差异表达及其在肿瘤中的作用。

结论

我们确定了一个新的自噬相关特征,该特征可能为 HNSCC 的治疗和预后提供有前途的生物标志物基因。我们需要通过将其应用于临床来验证其预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfc6/7591969/3c0c9d558862/DM2020-8899337.001.jpg

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