SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

Cancer Immunol Immunother. 2022 Feb;71(2):399-415. doi: 10.1007/s00262-021-02995-4. Epub 2021 Jun 28.

Abstract

Pulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

Keywords: Bioinformatics analysis; Immune infiltration; Immunotherapy; Prognosis; Surfactant protein A1.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology*
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Computational Biology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Prognosis
  • Pulmonary Surfactant-Associated Protein A / genetics
  • Pulmonary Surfactant-Associated Protein A / metabolism*
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Cells, Cultured
  • Tumor Microenvironment*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Pulmonary Surfactant-Associated Protein A
  • SFTPA1 protein, human