1. The Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021 P.R. China
2. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021 P.R. China
3. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021 P.R. China
*These authors contributed equally to this work.
Purpose: This study aimed to comprehensively investigate the differential expression and prognostic indicators of the tripartite motif-containing (TRIM) gene family in non-small cell lung cancer (NSCLC).
Methods: The Cancer Genome Atlas (TCGA) Research Network and three datasets from Gene Expression Omnibus (GEO) database were used to assess TRIM gene family expression patterns in NSCLC. Quantitative real-time PCR and immunohistochemistry (IHC) were conducted to confirm differentially expressed genes (DEGs). Kaplan-Meier survival analysis and univariate Cox regression analysis were carried out to analyze the association between TRIM gene expression and NSCLC prognoses. Gene set enrichment analysis (GSEA) was carried on for the predict the biological processes.
Results: Of the 78 TRIM family members measured, TRIM15 was selected due to the DEGs and the prognostic value regarding NSCLC. In lung squamous cell carcinoma (LUSC), the Log2 fold change (Log2FC) of TRIM15 was 5.16 (p= 0.00575), whereas in lung adenocarcinoma (LUAD), it was 6.37 (p =6.78E-07). TRIM15 upregulation was related to poor prognoses in both LUSC (HR 1.353; 95%CI 1.023-1.789; p =0.034) and LUAD (HR 1.560; 95%CI 1.159-2.101; p =0.003). Using immunohistochemistry, TRIM15 expression was significantly higher in NSCLC tissues compared with that of matched normal tissues (p =0.0009), and similar findings were generated with tissue microarray analysis (p<0.0001).
Conclusion: TRIM15 could act as a diagnostic predictor or therapeutic target for lung cancer treatments.
Keywords: Non-small cell lung cancer, E3 ubiquitin ligases, survival analysis, TRIM family genes, TRIM15