Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA prognostic biomarkers for...Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA 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 IncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify IncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified IncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results： We identified nine HNSCC-relevant IncRNAs 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. CY-I-OR 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 IncRNA 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 in- dependent 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 IncRNAs 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 IncRNAs in HNSCC as well as clinical applications.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.31471226 and 91440108)the Fundamental Research Funds for the Central Universities(Nos.WK2070000044 and WK2070000034),China
文摘Objective： In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma （HNSCC）-associated long noncoding RNAs （IncRNAs）, and to discover potential IncRNA 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 IncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify IncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified IncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. Results： We identified nine HNSCC-relevant IncRNAs 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. CY-I-OR 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 IncRNA 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 in- dependent 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 IncRNAs 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 IncRNAs in HNSCC as well as clinical applications.
