Guo Ya, Yang Peng Tao, Wang Zhong Wei, Xu Kun, Kou Wei Hua, Luo Heng
Department of Radiation Oncology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Front Oncol. 2021 Jan 26;10:603864. doi: 10.3389/fonc.2020.603864. eCollection 2020.
Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.
头颈部鳞状细胞癌（HNSCC）的预后较差。大量证据表明，自噬和非编码RNA在癌症相关生物学过程中发挥着重要作用，但自噬相关长链非编码RNA（lncRNA）与HNSCC之间的关联仍不清楚。在本研究中，从癌症基因组图谱数据库和人类自噬数据库中提取了HNSCC RNA序列和自噬相关基因数据。通过计算Pearson相关系数，共筛选出1153个自噬相关lncRNA。通过单因素Cox回归、最小绝对收缩和选择算子分析以及多因素Cox回归分析，鉴定出3个与预后相关的自噬lncRNA。我们还基于这些自噬相关lncRNA构建了一个预后模型，并评估了其准确独立预测HNSCC患者预后的能力。曲线下面积（AUC）在3年时为0.864，5年时为0.836，我们的模型能够独立预测HNSCC的预后。通过对来自五个数据库的样本进行分析，证实了这3个自噬lncRNA的预后价值。为了进一步确定这3个lncRNA的功能，构建了共表达网络并进行了通路分析。在该分析中，lncRNA与189个相关基因和20个自噬相关基因相关，这些lncRNA主要涉及同源重组、范可尼贫血通路、自噬相关通路和免疫相关通路。此外，基于TIMER、Oncomine和HPA数据库分析，我们验证了3个lncRNA和自噬标志物（ATG12、BECN1和MAP1LC3B）的表达水平。我们的结果表明，TTTY15在HPV阳性和HPV阴性HNSCC患者中均升高，并且在所有HNSCC患者中3个自噬标志物均上调。最后，对3个lncRNA与自噬标志物之间的关联进行了分析，结果显示TTTY15和MIF-AS1与自噬标志物相关。总的来说，这些结果表明3个自噬相关lncRNA对HNSCC患者具有预后价值。
