Construction of an m6A-related lncRNA pair prognostic signature and prediction of the immune landscape in head and neck squamous cell carcinoma

J Clin Lab Anal. 2022 Jan;36(1):e24113. doi: 10.1002/jcla.24113. Epub 2021 Nov 16.

Abstract

Background: Mounting evidence indicates that aberrantly expressed N6-methylandenosine (m6A) modification regulators and long noncoding RNA (lncRNA) influence the development of head and neck squamous cell carcinoma (HNSCC). However, the prognosis of m6A-related lncRNA (mrlncRNA) in HNSCC has not yet been evaluated.

Methods: We retrieved transcriptome, somatic mutation, and clinical information from The Cancer Genome Atlas database and established a differently expressed mrlncRNA (DEmrlncRNA) pair signature based on least absolute shrinkage and selection operator Cox regression and multivariate Cox analyses. Each sample's risk score was computed premised on the signature, which accurately classified patients into low- and high-risk group by the cut-off point. The signature was evaluated from the perspective of survival, clinicopathological characteristics, tumor mutation burden (TMB), immune cell infiltration, efficacy of chemotherapeutics, tumor immune microenvironment, and immune checkpoint inhibitor (ICI)-related genes.

Results: 11 DEmrlncRNA pairs were identified and were used to construct the prediction signature. Kaplan-Meier plotter revealed a worse prognosis in high-risk patients over low-risk patients (log rank p < 0.001). According to multivariate Cox regression analysis, the hazard ratio of the risk score and 95% confidence interval of 1.722 and (1.488-1.992) (p < 0.001) were obtained. Furthermore, an increased risk score was associated with aggressive clinicopathological features, specific tumor immune infiltration status, increased expression of ICI-related genes, higher TMB, and higher chemotherapeutics sensitivity (all p < 0.05).

Conclusion: This research demonstrated that the signature premised on DEmrlncRNA pairs was an efficient independent prognostic indicator and may provide a rationale for research on immunotherapeutic and chemotherapeutics strategies for HNSCC patients.

Keywords: N6-methylandenosine; head and neck squamous cell carcinoma; immunotherapy; long non-coding RNA; prognosis.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Biomarkers, Tumor / genetics
  • Head and Neck Neoplasms* / diagnosis
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / mortality
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immunotherapy
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Squamous Cell Carcinoma of Head and Neck* / diagnosis
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Squamous Cell Carcinoma of Head and Neck* / therapy
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • N-methyladenosine
  • Adenosine