摘要

  头颈部鳞状细胞癌 (HNSCC) 是全球最常见的癌症之一，占发展中国家所有恶性肿瘤的近 50%。自噬在癌症的发生、恶性进展和对治疗的抵抗中起着至关重要的作用。然而，很少在 HNSCC 中分析自噬相关基因集。因此，有必要在更大的 HNSCC 患者队列中评估其临床和病理意义。本研究的目的是为 HNSCC 建立一种新的自噬相关预后标志物。我们筛选了 232 个自噬相关基因 (ARG)，并在癌症基因组图谱 (TCGA) 队列中鉴定了 38 个差异表达的 ARG。使用单变量和多变量 Cox 比例回归模型建立的预后相关 ARG 特征由 10 个 ARG 组成，可将患者分为高风险组和低风险组。生存分析表明，与低风险患者相比，高风险组患者的总生存期显着缩短。 Cox回归分析进一步证实了自噬相关特征的独立预后价值，联合预后模型的受试者工作特征曲线下面积为0.722。最后，自噬相关特征的功效也得到了来自基因表达综合 (GEO) 数据库的独立队列的验证。总的来说，我们成功构建了一个新的自噬相关特征，用于预测 HNSCC 患者的预后。

  Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, accounting for almost 50% of all malignancies in developing nations. Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment. However, autophagy-related gene sets have rarely been analyzed in HNSCC. Hence, it is necessary to assess its clinical and pathological significance in a larger cohort of patients with HNSCC. The purpose of this study was to establish a novel autophagy-related prognostic marker for HNSCC. We screened 232 autophagy-related genes (ARGs) and identified 38 differentially expressed ARGs in The Cancer Genome Atlas (TCGA) cohorts. The prognosis-related ARGs signature, established using the univariate and multivariate Cox proportional regression models, consists of 10 ARGs that could divide patients into high-risk and low-risk groups. Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with their low-risk counterparts. Cox regression analysis further confirmed the independent prognostic value of the autophagy-related signature, and the area under the receiver operating characteristic curve of the combined prognostic model was 0.722. Finally, the efficacy of autophagy-related signature was also validated by an independent cohort from the Gene Expression Omnibus (GEO) database. Collectively, we successfully constructed a novel autophagy-related signature for the prediction of prognosis in patients with HNSCC.

  https://www.nature.com/articles/s41420-020-00294-y