Abstract
Objective: In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. Methods: RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA), including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated lncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify lncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified lncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results: We identified nine HNSCC-relevant lncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CYTOR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival (OS) and disease free survival (DFS) of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum (DDP). HCG22, the most dramatically down-regulated lncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values independent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings. Conclusions: Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated lncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these lncRNAs in HNSCC as well as clinical applications.
摘要
目的
研究长链非编码RNA(lncRNA)与头颈部肿瘤 发生、发展及预后的关系。
创新点
通过使用整合的转录组分析方法筛选出与头颈部 肿瘤密切相关的lncRNA,其中CYTOR和HCG22 在头颈部肿瘤发生发展中具有重要的生物学功 能和临床预后价值,为制定新的治疗策略和探索 新的预后标记分子提供参考。
方法
从癌症基因组数据集(The Cancer Genome Atlas) 中获得RNA-seq 数据。结合差异表达分析和共 表达网络分析的方法发掘出与头颈部鳞状细胞 癌相关的lncRNA,探讨其与头颈部肿瘤临床病 理变化和预后的关系,进一步利用外部数据集以 及细胞水平进行验证。
结论
发现9 个与头颈部肿瘤发生发展密切相关的 lncRNA,其中CYTOR 可能参与核糖体的生物合 成,与病人生存率呈负相关。HCG22 可能参与 细胞表皮分化过程,与病人生存率呈正相关。此 外,CYTOR 和HCG22 可作为头颈部鳞状细胞癌 独立的预后标记物。
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Project supported by the National Natural Science Foundation of China (Nos. 31471226 and 91440108) and the Fundamental Research Funds for the Central Universities (Nos. WK2070000044 and WK2070000034), China
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Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma
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Guo, Yz., Sun, Hh., Wang, Xt. et al. Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma. J. Zhejiang Univ. Sci. B 19, 674–688 (2018). https://doi.org/10.1631/jzus.B1700319
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DOI: https://doi.org/10.1631/jzus.B1700319
Key words
- Head and neck squamous cell carcinoma
- Long noncoding RNA (lncRNA)
- Weighted gene co-expression network analysis (WGCNA)
- Clinicopathological feature
- Multivariate Cox regression model