Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis

Front Immunol. 2022 Feb 24:13:843467. doi: 10.3389/fimmu.2022.843467. eCollection 2022.

Abstract

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the world's most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated.

Methods: The multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated.

Results: Patients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient's immune infiltration phenotype using 16 genes' expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts.

Conclusions: In this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy's outcome.

Keywords: TCGA; head and neck cancer; immune infiltration; immunology; laryngeal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Butyrophilins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms* / genetics
  • MicroRNAs*
  • Phenotype
  • Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

  • Antigens, CD
  • BTN3A1 protein, human
  • Butyrophilins
  • MIRN149 microRNA, human
  • MicroRNAs