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LAGE3 correlates with tumorigenic immune infiltrates in the clear cell renal cell carcinoma microenvironment
Xubin Dong1, Dian-Na Gu2, Ouchen Wang1
1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, #1 Nan Bai Xiang Street, Wenzhou 325006, China.
Objective:
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. The role of LAGE3 (L Antigen Family Member 3) in ccRCC has not been widely reported. In this study, we explored the clinical significances and biological functions of LAGE3 in ccRCC.
Methods:
The RNA-seq data and the corresponding clinical information of the patients with ccRCC were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ESTIMATE, quanTiseq, and xCell algorithms were used to estimate the immune infiltration levels in the ccRCC microenvironment.
Results:
We found that overexpression of LAGE3 was associated with adverse clinical-pathological factors, and correlated with poor prognosis in multiple ccRCC cohorts. Multivariate analysis indicated that LAGE3 was an independent survival determinant in patients with ccRCC, whereas functional enrichment analysis suggested that LAGE3 may regulate humoral immune response, immunoglobulin complex, and receptor-ligand activity. Further, tumor microenvironment analysis based on different algorithms indicated LAGE3 was positively associated with the immune activity and infiltrating levels of different immune cells. Particularly, LAGE3 expression had a positive impact on different steps of the cancer-immunity cycle.
Conclusion:
The present findings disclose that LAGE3 could be an independent survival predictor, and might contribute to developing novel ccRCC immunological treatment strategies.
Insights
LAGE3 (L Antigen Family Member 3) overexpression is linked to poor prognosis in clear cell renal cell carcinoma (ccRCC). This gene may serve as an independent survival predictor and a target for novel ccRCC immunotherapies.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the predominant kidney cancer globally.
- The role of L Antigen Family Member 3 (LAGE3) in ccRCC remains largely unexplored.
- Understanding LAGE3's function is crucial for advancing ccRCC treatment.
Purpose of the Study:
- To investigate the clinical significance of LAGE3 in ccRCC.
- To elucidate the biological functions of LAGE3 within the ccRCC tumor microenvironment.
- To assess LAGE3 as a potential prognostic biomarker and therapeutic target.
Main Methods:
- Utilized RNA-sequencing data and clinical information from TCGA and GEO databases for ccRCC patients.
- Employed ESTIMATE, quanTiseq, and xCell algorithms to analyze immune cell infiltration.
- Conducted multivariate analysis and functional enrichment analysis.
Main Results:
- LAGE3 overexpression correlated with unfavorable clinical-pathological features and poorer survival outcomes in ccRCC cohorts.
- LAGE3 was identified as an independent determinant of survival in ccRCC patients.
- Functional analysis suggested LAGE3 influences humoral immune responses and receptor-ligand activity, positively impacting the cancer-immunity cycle and immune cell infiltration.
Conclusions:
- LAGE3 serves as a significant independent survival predictor for ccRCC.
- LAGE3 expression is associated with immune activity within the tumor microenvironment.
- Targeting LAGE3 may offer potential for developing new immunotherapeutic strategies for ccRCC.
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