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BIRC5 expression correlates with immunosuppressive phenotype and predicts inferior response to immunotherapy in lung
Shuo Yang1, Xiaozhen Liu1, Shiqi Mao1
1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background:
BIRC5, also known as survivin, is the smallest but functionally most complex member of the inhibitor of apoptosis protein (IAP) family and plays an important role in tumorigenesis, recurrence, and chemoresistance, this study aimed to investigate its impact on the clinical and tumor microenvironmental features of lung adenocarcinoma (LUAD), together with its prognostic values.
Methods:
Clinical and transcriptomic data of 535 LUAD samples, 59 normal lung, and 54 patients with non-small cell lung cancer (NSCLC) received immune checkpoint blockades (ICBs) were analyzed. Immune infiltration analysis was conducted to uncover the relationship between tumor microenvironmental features and BIRC5 expression level. The prognostic values of BIRC5 were also evaluated with log-rank test and Cox regression analysis.
Results:
LUAD had a significantly higher BIRC5 expression level than normal lung tissues. The elevated BIRC5 expression was markedly associated with unfavorable clinical outcomes. Transcriptomic and single-cell sequencing data analysis revealed that tumors with high BIRC5 expression was correlated with multiple pathways' enrichment. Immune infiltration analysis indicated a negative correlation between BIRC5 expression and infiltration levels of CD8+ T cells, dendritic cells (DCs), and natural killer (NK) cell in LUAD, but a positive correlation was observed between BIRC5 expression and regulatory T cells (Tregs) infiltrations. Importantly, NSCLC patients received ICB with high BIRC5 expression had dramatically shorter progression-free survival (PFS; 1.2 vs. 4.5 months; P=0.01) and overall survival (OS; 3.1 vs. 12.7 months; P=0.005) than those with low BIRC5 expression.
Conclusions:
These findings suggested that high BIRC5 expression was associated with DNA damage/repair, cell invasion and proliferation related pathways enrichment and increased Tregs infiltration, which would result in inferior outcomes in NSCLC received ICB.
Insights
High survivin (BIRC5) expression in lung adenocarcinoma correlates with poor prognosis and reduced immune cell infiltration. This indicates BIRC5 may predict poor response to immune checkpoint blockades in non-small cell lung cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Survivin (BIRC5) is a key protein in the inhibitor of apoptosis protein family, implicated in cancer development and treatment resistance.
- Understanding BIRC5's role in lung adenocarcinoma (LUAD) is crucial for predicting clinical outcomes and response to therapies.
Purpose of the Study:
- To investigate the impact of BIRC5 expression on clinical features and the tumor microenvironment in LUAD.
- To evaluate the prognostic value of BIRC5 in LUAD and its predictive role in non-small cell lung cancer (NSCLC) treated with immune checkpoint blockades (ICBs).
Main Methods:
- Analysis of clinical and transcriptomic data from 535 LUAD samples and 54 NSCLC patients receiving ICBs.
- Immune infiltration analysis to correlate BIRC5 levels with tumor microenvironmental features.
- Prognostic evaluation using log-rank tests and Cox regression analysis.
Main Results:
- LUAD tissues exhibited significantly higher BIRC5 expression compared to normal lung tissues, associated with poorer clinical outcomes.
- High BIRC5 expression correlated with enrichment of DNA damage/repair, invasion, and proliferation pathways.
- BIRC5 expression negatively correlated with CD8+ T cells, dendritic cells, and NK cells, but positively with regulatory T cells (Tregs).
- NSCLC patients with high BIRC5 expression receiving ICBs showed significantly shorter progression-free survival (PFS) and overall survival (OS).
Conclusions:
- Elevated BIRC5 expression in LUAD is linked to aggressive tumor characteristics and immune evasion via increased Tregs.
- High BIRC5 expression predicts inferior outcomes in NSCLC patients treated with ICBs, highlighting its potential as a predictive biomarker.
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