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Published on: January 19, 2019
p62/SQSTM1 impairs immunotherapy in lung adenocarcinoma by suppressing immune infiltration and peripheral immune
Haoran Li1, Huamin Qin2, Qinghan Xin3
1Department of Breast Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Purpose:
We aim to find a potential immunotherapeutic target for lung adenocarcinoma (LUAD) patients.
Methods:
We collected 193 normal and 543 LUAD tumor samples in total from GEO database. ESTIMATE algorithm, limma and ssGSEA methods were used to find immune-related differential expression genes and to quantify the immune infiltration levels. Preclinical experiments were performed to confirm the role of p62 on LUAD cell lines. And retrospective cohort analyses were used to discover the relationship between p62 and LUAD patients' peripheral immune status, tumor immune infiltration levels and prognosis of immunotherapy.
Results:
We confirmed that p62 was overexpressed in LUAD patients whose expression corresponded with lower survival. Simultaneously, we discovered an association of p62 with immune cells, wherein high p62 expression in LUAD patients corresponded with fewer tumor-infiltrating lymphocytes, again associated with a poorer prognosis. We revealed that p62 significantly promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro. Moreover, we found that p62 somatic copy number alterations corresponded with tumor infiltration of immune cells. In addition, both expression and methylation level of p62 were significantly correlated with immune cell infiltration. Importantly, we demonstrated in a small cohort of LUAD patients receiving immune checkpoint inhibitors (ICIs) that p62 levels were negatively associated with lower levels of circulating and infiltrated lymphocytes and shorter progression-free survival of ICI treatment.
Conclusion:
We demonstrated the involvement of p62 in immune cell infiltration and peripheral immune cell status in LUAD, as well as preliminarily characterized its roles in cancer progression, thus identifying a potential prediction and prognostic marker for LUAD immunotherapy.
Insights
p62 is overexpressed in lung adenocarcinoma (LUAD), correlating with poorer survival and reduced immune cell infiltration. Targeting p62 may improve immunotherapy outcomes for LUAD patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Lung adenocarcinoma (LUAD) remains a significant health concern with limited treatment options.
- Identifying novel therapeutic targets is crucial for improving patient outcomes in LUAD.
- Understanding the tumor microenvironment and immune cell infiltration is key to developing effective immunotherapies.
Purpose of the Study:
- To investigate the role of p62 in LUAD.
- To determine if p62 can serve as an immunotherapeutic target or prognostic marker for LUAD patients.
- To explore the association between p62 expression and immune cell infiltration in LUAD.
Main Methods:
- Analysis of gene expression data from GEO database for 193 normal and 543 LUAD samples.
- Utilized ESTIMATE, limma, and ssGSEA algorithms to assess immune infiltration levels.
- Performed in vitro experiments on LUAD cell lines and retrospective cohort analyses.
Main Results:
- p62 was found to be overexpressed in LUAD, associated with lower survival rates.
- High p62 expression correlated with reduced tumor-infiltrating lymphocytes and poorer prognosis.
- p62 promoted cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition.
- p62 alterations and levels were significantly correlated with immune cell infiltration and methylation.
- In a cohort receiving immune checkpoint inhibitors (ICIs), high p62 levels were linked to reduced lymphocyte levels and shorter progression-free survival.
Conclusions:
- p62 plays a significant role in LUAD progression and immune evasion.
- p62 is a potential predictive and prognostic biomarker for LUAD immunotherapy.
- Targeting p62 may represent a novel strategy for enhancing LUAD immunotherapy efficacy.
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