Abstract
Studies have shown that long non-coding RNA (lncRNA) may act as the carcinogenic factor or tumor suppressor of laryngeal squamous cell carcinoma (LSCC). This study aims to identify the prognostic value and potential target protein-coding genes (PCGs) of lncRNAs in LSCC. The LSCC datasets were collected from The Cancer Genome Atlas (TCGA). Statistical and bioinformatic methods were used to establish and evaluate the prognostic model, identify the correlation between lncRNAs and clinical characteristics, and screen for PCGs co-expressed with lncRNAs. Weighted gene co-expression network analysis (WGCNA) identified PCG modules associated with clinical characteristics. The expression of lncRNAs and PCGs was analyzed using our LSCC patients by RT-qPCR. LINC02154, LINC00528, SPRY4-AS1, TTTY14, LNCSRLR, and KLHL7-DT were selected to establish the prognostic model. The overall survival (OS) of low-risk patients forecasted by the model was significantly better than high-risk patients. Receiver operating characteristic (ROC) curve and concordance index (C-index) validated the accuracy of the prognostic model. Chi-square test showed that six lncRNAs were associated with one of the clinical characteristics, i.e., gender, clinical stage, T and N stage, respectively. WGCNA identified PCG modules associated with gender, clinical stage, T and N stage. We took the intersection of the PCG modules of WGCNA, the differentially expressed PCGs between LSCC and normal samples, and the PCGs co-expressed with six lncRNAs. The intersection PCGs survival analysis showed that four PCGs, i.e., STC2, TSPAN9, SMS, and TCEA3 affected the OS of LSCC. More importantly, the differential expression of six lncRNAs and four PCGs between LSCC and normal samples was verified by our LSCC patients. In conclusion, we successfully established a prognostic model based on six-lncRNA RiskScore and initially screened the potential target PCGs of six lncRNAs for further basic and clinical research.
Highlights
Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck squamous cell carcinomas (Solomon et al, 2018), originating from the larynx epithelium, with high metastatic rate and poor prognosis (Bingol et al, 2016)
We identified for the first time the six-Long non-coding RNA (lncRNA) signature as predictors of LSCC patient survival risk, using a cohort of LSCC cases from The Cancer Genome Atlas (TCGA) database
4435 differentially expressed protein-coding genes (PCGs) (Supplementary Table 5) were identified (LSCC compared with normal samples)
Summary
Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck squamous cell carcinomas (Solomon et al, 2018), originating from the larynx epithelium, with high metastatic rate and poor prognosis (Bingol et al, 2016). Most LSCC patients are locally advanced when they are first diagnosed, with a 5-year survival rate of approximately 50% (Chan et al, 2018). Studies have shown that lncRNA regulates mRNA through multiple patterns. LncRNA can directly bind to mRNA leading to the recruitment of the RNA-binding proteins (RBPs) that promote decay, the RBPs that suppress translation, or factors that initiate translation. LncRNA can serve as ‘decoys’ for RBPs, dissociating RBPs from target mRNAs, and thereby influencing the abundance and translation of such mRNAs (Noh et al, 2018). Studies have shown that lncRNAs are associated with OS in patients with LSCC (Shen et al, 2014), but the prognostic value of a single candidate lncRNA biomarker is limited. In view of this, combining a series of lncRNAs is more significant in predicting the prognosis of LSCC
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