CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820970663. doi: 10.1177/1533033820970663.

Abstract

Objective: Precision immunotherapy in non-small cell lung cancer (NSCLC) have been the focus of tumor immunity research. The aim of this study is to identify novel candidate biomarkers predicting the response to immunotherapy in NSCLC.

Methods: GSE126044 was obtained from Gene Expression Omnibus (GEO). According to the response to anti-PD-1 antibody, 2 groups were divided: response group and non-response group. Differentially expressed genes (DEGs) were screened using R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. ROC curves and possible pathways of the seed genes were further analyzed.

Results: In total, 588 DEGs (487 upregulated DEGs and 101 downregulated) were identified. GO and KEGG analyses showed that upregulated DEGs were mainly enriched in immune response and cell adhesion pathways, while VEGF signaling pathway and metabolic pathways were mainly enriched in downregulated DEGs. In addition, CSF1 R and HCST showed more powerful predictive ability than PDL1. More importantly, these candidate genes were not only positively correlated with the expression of PDL1 and the infiltration of CD8+ T cells in the immune microenvironment, but also might improve the prognosis in lung squamous cell carcinoma.

Conclusions: CSF1 R and HCST might be novel predictive markers for immunotherapy in NSCLC.

Keywords: biomarker; data mining; immunotherapy; lung cancer.

MeSH terms

  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Computational Biology
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Immunotherapy
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / etiology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / therapy
  • Prognosis
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • ROC Curve
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • CSF1R protein, human
  • HCST protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptors, Immunologic