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.
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Acknowledgement
The authors thank Yifan Yang for her help in this study and TCGA platform for cancer genomics data sets. The research was supported by Shanghai Anticancer Association (SACA-AX106 to Yu Wang) and Shanghai Anticancer Association (SACA-AX106 to Yu Wang and SACA-CY19B01 to Ben Ma).
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Supplementary Figure 1
. The enrichment biological cancer related pathway of each lncRNA based on the GSEA of TCGA cohort. (A) The enrichment biological cancer related pathway of AC126175.1 based on the GSEA of TCGA cohort. (B) The enrichment biological cancer related pathway of AL139327.21 based on the GSEA of TCGA cohort. (C). The enrichment biological cancer related pathway of LINC02434 based on the GSEA of TCGA cohort.
Supplementary Figure 2
. Kaplan-Meier curves for early stage (stage I/II) and advanced stage (stage III/IV). (A) Kaplan-Meier curves for early stage (stage I/II). (B) Kaplan-Meier curves for advanced stage (stage III/IV).
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Jiang, H., Ma, B., Xu, W. et al. A Novel Three-lncRNA Signature Predicts the Overall Survival of HNSCC Patients. Ann Surg Oncol 28, 3396–3406 (2021). https://doi.org/10.1245/s10434-020-09210-1
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DOI: https://doi.org/10.1245/s10434-020-09210-1