Hongyi Jiang1,2, Ben Ma1,2, Weibo Xu1,2, Yi Luo1,2, Xiao Wang1,2, Shishuai Wen1,2, Tian Liao1,2, Zhongwu Lu1,2, Shuwen Yang3,4, Yu Wang5,6. 1. Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. 3. Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. ysw430@163.com. 4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. ysw430@163.com. 5. Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. neck130@sina.com. 6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. neck130@sina.com.
Abstract
BACKGROUND: A number of long non-coding RNAs (lncRNAs) have been found to be involved in tumor progression and associated with disease prognoses in various types of cancer. Our study identified a novel three-lncRNA signature to predict survival of head and neck squamous cell caner (HNSCC) patients. METHODS: We utilized The Cancer Genome Atlas (TCGA) cohort to screen out overall survival (OS)-associated lncRNAs in HNSCC and further developed a model to identify a lncRNA signature for evaluating disease status and prognosis. The lncRNA signature was then validated in HNSCC patients from our Fudan University Shanghai Cancer Center (FUSCC) cohort. RESULTS: LINC02434, AL139327.2, and AC126175.1 were identified by multivariable Cox regression analyses of independent risk factors for deceased status. We built a risk score model based on the three-lncRNA signature using coefficient of multivariable Cox regression and expression value of the three lncRNAs. The high-risk signature score was significantly associated with decreased OS in both the TCGA cohort and the FUSCC cohort. The high-risk group had worse overall survival than the low-risk group in TCGA cohort. To further validate the robustness of three-lncRNA signature risk score model developed in the TCGA dataset, the performance of risk score also evaluated in our institute FUSCC cohort. Additionally, the signature score showed a positive correlation with aggressive outcomes of HNSCC, such as III/IV stage, TP53 mutation, and PI3KCA mutation. The gene set enrichment analysis indicates that the risk score is associated with cancer metastasis-related pathways. Several cancer-related pathways, such as epithelial mesenchymal transition, TNFα signaling via NF-κB, MYC targets, and angiogenesis. CONCLUSIONS: The three-lncRNA signature could provide a novel prediction insight into the prognosis of HNSCC patients. The three-lncRNA signature was identified as a predictor of poor prognoses in HNSCC, which may serve as a potential therapeutic target.
BACKGROUND: A number of long non-coding RNAs (lncRNAs) have been found to be involved in tumor progression and associated with disease prognoses in various types of cancer. Our study identified a novel three-lncRNA signature to predict survival of head and neck squamous cell caner (HNSCC) patients. METHODS: We utilized The Cancer Genome Atlas (TCGA) cohort to screen out overall survival (OS)-associated lncRNAs in HNSCC and further developed a model to identify a lncRNA signature for evaluating disease status and prognosis. The lncRNA signature was then validated in HNSCC patients from our Fudan University Shanghai Cancer Center (FUSCC) cohort. RESULTS:LINC02434, AL139327.2, and AC126175.1 were identified by multivariable Cox regression analyses of independent risk factors for deceased status. We built a risk score model based on the three-lncRNA signature using coefficient of multivariable Cox regression and expression value of the three lncRNAs. The high-risk signature score was significantly associated with decreased OS in both the TCGA cohort and the FUSCC cohort. The high-risk group had worse overall survival than the low-risk group in TCGA cohort. To further validate the robustness of three-lncRNA signature risk score model developed in the TCGA dataset, the performance of risk score also evaluated in our institute FUSCC cohort. Additionally, the signature score showed a positive correlation with aggressive outcomes of HNSCC, such as III/IV stage, TP53 mutation, and PI3KCA mutation. The gene set enrichment analysis indicates that the risk score is associated with cancer metastasis-related pathways. Several cancer-related pathways, such as epithelial mesenchymal transition, TNFα signaling via NF-κB, MYC targets, and angiogenesis. CONCLUSIONS: The three-lncRNA signature could provide a novel prediction insight into the prognosis of HNSCC patients. The three-lncRNA signature was identified as a predictor of poor prognoses in HNSCC, which may serve as a potential therapeutic target.
Authors: Martin L Read; Bhavika Modasia; Alice Fletcher; Rebecca J Thompson; Katie Brookes; Peter C Rae; Hannah R Nieto; Vikki L Poole; Sally Roberts; Moray J Campbell; Kristien Boelaert; Andrew S Turnell; Vicki E Smith; Hisham Mehanna; Christopher J McCabe Journal: Cancer Res Date: 2018-08-28 Impact factor: 12.701