4.7 Article

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

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 71, Issue 2, Pages 399-415

Publisher

SPRINGER
DOI: 10.1007/s00262-021-02995-4

Keywords

Surfactant protein A1; Prognosis; Immune infiltration; Immunotherapy; Bioinformatics analysis

Funding

  1. National Natural Science Foundation of China [81870026, 81602685, 81672992]
  2. Clinical Research Startup Program of Southern Medical University [LC2016PY006, LC2019ZD008]
  3. Clinical Research Program of Nanfang Hospital, Southern Medical University [2018CR019, 2018CR021]
  4. Health & Medical Collaborative Innovation Project of Guangzhou City, China [201803040003]

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SFTPA1 protein plays a critical role in maintaining lung tissue homeostasis and the innate immune response, with its high expression associated with a favorable prognosis in lung adenocarcinoma. It may serve as a potential biomarker for predicting a positive response to immunotherapy in lung cancer patients.
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.

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