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. 2020 Feb 13:8:e8557.
doi: 10.7717/peerj.8557. eCollection 2020.

LINC00958 and HOXC13-AS as key candidate biomarkers in head and neck squamous cell carcinoma by integrated bioinformatics analysis

Dan Xiong  1 , Wei Wu  1 , Lijuan Kan  1 , Dayang Chen  1 , Xiaowen Dou  1 , Xiang Ji  1 , Mengmeng Wang  1 , Zengyan Zong  1 , Jian Li  2   3 , Xiuming Zhang  1
Affiliations

LINC00958 and HOXC13-AS as key candidate biomarkers in head and neck squamous cell carcinoma by integrated bioinformatics analysis

Dan Xiong et al. PeerJ. .

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with a strong tendency for metastasis and recurrence. Finding effective biomarkers for the early diagnosis of HNSCC is critical for the early treatment and prognosis of patients.

Methods: RNA sequencing data including long non-coding RNAs (lncRNAs), messenger RNA (mRNAs) and microRNAs (miRNAs) of 141 HNSCC and 44 adjacent normal tissues were obtained from the TCGA. Differentially expressed genes were analyzed using the R package DESeq. GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. A competing endogenous RNAs (ceRNA) network was constructed. The most differentially expressed genes in the main ceRNA network were chosen for nasopharyngeal carcinoma (NPC) cell lines and NPEC2 Bmi-1 cell line verification. A receiver operating characteristic (ROC) curve was constructed for 141 specimens of HNSCC tissues from 44 control samples.

Results: In our study, 79 HNSCC-associated abnormally expressed lncRNAs , 86 abnormally expressed miRNAs and 324 abnormally expressed mRNAs were identified. The public microarray results showed that LINC00958 and HOXC13-AS expression levels were upregulated in HNSCC tissues compared with the adjacent normal tissues in this study (p < 0.0001). LINC00958 and HOXC13-AS expression levels in NPC cell lines were higher than those in the NPEC2 Bmi-1 cell line (p < 0.05). The results showed that the area under the ROC curve (AUC) of LINC00958 reached up to 0.906 at a cutoff value of 7.96, with a sensitivity and specificity of 80.85% and 90.91%, respectively. The AUC of HOXC13-AS reached up to 0.898 at a cutoff value of 0.695, with sensitivity and specificity values of 86.23% and 83.78%, respectively.

Conclusion: The current study indicates that LINC00958 and HOXC13-AS are new candidate diagnostic biomarkers for HNSCC patients.

Keywords: Biomarkers; HNSCC; HOXC13-AS; LINC00958.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. The flow chart for bioinformatics analysis in this study.
Figure 2
Figure 2. Cluster analysis of 15 up- and down-regulated differentially expressed lncRNAs, microRNA and mRNAs in HNSCC tissues and adjacent normal tissues from TCGA database.
Hierarchical clustering analysis indicated that 15 up- and down-regulated differentially expressed lncRNAs (A), microRNA (B) and mRNAs (C) were differentially expressed between HNSCC patients and healthy controls, respectively. The red and the green shades represent the expression levels above and below the relative expression among all samples.
Figure 3
Figure 3. The 20 key gene ontology (GO) terms and KEGG pathway enrichment of differentially expressed intersection mRNAs for HNSCC groups versus adjacent normal controls.
(A) The 20 key Gene Ontology terms in up-regulated differentially expressed genes, the bar plot shows the enrichment scores of the significant enrichment GO terms. (B) The 20 key Gene Ontology terms in down-regulated, differentially expressed genes, the bar plot shows the enrichment scores of the significant enrichment GO terms. (C) The 20 key pathways in up-regulated differentially expressed genes, the bar plot shows the enrichment scores of the significant enrichment pathways. (D) The 20 key pathways in down-regulated differentially expressed genes. The bar plot shows the enrichment scores of the significant enrichment pathways.
Figure 4
Figure 4. The ceRNA network of lncRNA–miRNA–mRNA in HNSCC.
The red represents the upregulated, and the green represents the downregulated. Diamonds represent miRNAs, balls represent mRNAs, and triangles represent lncRNAs.
Figure 5
Figure 5. PPI network of 72 upregulated and 19 downregulated DEGs.
Nodes represent proteins and edges represent interactions between two proteins. Red nodes represent upregulated DEGs and green nodesrepresent downregulated DEGs.
Figure 6
Figure 6. LINC00958 and HOXC13-AS expression levels in tumors and cells.
(A–B) Enhanced expression of LINC00958 and HOXC13-AS expression levels in HNSCC tissues compared with adjacent normal tissues (n = 44, T = 141, p < 0.0001). (C-D) LINC00958 and HOXC13-AS expression levels in NPC cell lines were higher than that in NPEC2 Bmi-1 which was immortalized nasopharyngeal epithelial cells induced by Bmi-1. (E–F) The ROC curve of LINC00958 and HOXC13-AS between HNSCC tissues and controls.
See this image and copyright information in PMC

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