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Transcriptomic model-based lncRNAs and mRNAs serve as independent prognostic indicators in head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSC) is one of most common types of cancer worldwide, and mRNAs and long non-coding RNAs (lncRNAs) have been identified as prognostic biomarkers in HNSC. In the present study, using gene expression datasets from multiple platforms, survival-associated genes in HNSC were identified. Subsequently, a combination of 17 genes (14 mRNAs and 3 lncRNA) was optimized using random forest variable hunting and a risk score model for HNSC prognosis was developed using a cohort from The Cancer Genome Atlas. Patients with high-risk scores tend to have earlier disease recurrence and lower survival rates, compared with those with low-risk scores. This observation was further validated in three independent datasets (GSE41613, GSE10300 and E-MTAB-302). Association analysis revealed that the risk score is independent of other clinicopathological observations. On the basis of the results depicted in the nomogram, the risk score performs better in 3-year survival rate prediction than other clinical observations. In summary, the lncRNA-mRNA signature-based risk score successfully predicts the survival of HNSC and serves as an indicator of prognosis.

SUBMITTER: Zhang ZL

PROVIDER: S-EPMC6507369 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Transcriptomic model-based lncRNAs and mRNAs serve as independent prognostic indicators in head and neck squamous cell carcinoma.

Zhang Zhi-Li ZL Zhao Li-Jing LJ Xu Lin L Chai Liang L Wang Feng F Xu Ya-Ping YP Zhou Shui-Hong SH Fu Yong Y

Oncology letters 20190404 6

Head and neck squamous cell carcinoma (HNSC) is one of most common types of cancer worldwide, and mRNAs and long non-coding RNAs (lncRNAs) have been identified as prognostic biomarkers in HNSC. In the present study, using gene expression datasets from multiple platforms, survival-associated genes in HNSC were identified. Subsequently, a combination of 17 genes (14 mRNAs and 3 lncRNA) was optimized using random forest variable hunting and a risk score model for HNSC prognosis was developed using ...[more]

PMID: 31186775

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Project description:ObjectiveIn this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq.MethodsRNA-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 lncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify lncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified lncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis.ResultsWe identified nine HNSCC-relevant lncRNAs 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. CYTOR 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 lncRNA 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 independent 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.ConclusionsOur transcriptomic analysis suggested that dysregulation of these HNSCC-associated lncRNAs 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 lncRNAs in HNSCC as well as clinical applications.

Project description:Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

Dataset Information

Transcriptomic model-based lncRNAs and mRNAs serve as independent prognostic indicators in head and neck squamous cell carcinoma.

Publications

Transcriptomic model-based lncRNAs and mRNAs serve as independent prognostic indicators in head and neck squamous cell carcinoma.

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