KEY TAKEAWAYS
- The study aimed to investigate the role of eIF3a in DLBCL progression and assess its prognostic and therapeutic implications.
- Researchers noticed the significant prognostic and therapeutic implications of eIF3a in patients with DLBCL.
One-third of patients with diffuse large B-cell lymphoma (DLBCL) suffer relapse after standard treatment. Eukaryotic initiation factor 3a (eIF3a) is a key player in the initial stage of translation, which has been widely reported to be correlated with tumorigenesis and therapeutic response.
Hongkun Sun and the team aimed to explore the biological role of eIF3a and evaluate its prognostic and therapeutic potential in DLBCL.
They performed an inclusive analysis utilizing RNA-seq datasets from the GEO database to detect the expression and prognostic role of eIF3a in DLBCL patients. Protein levels of eIF3a were estimated through western blot and immunohistochemical methods. DLBCL cells were transfected with lentiviral vectors, either eIF3a-knockdown or empty, to assess the biological role of eIF3a.
Subsequently, the samples were divided into two clusters based on eIF3a expression and differentially expressed genes (DEGs) were identified. Function enrichment and mutation analysis of DEGs were employed to detect potential biological roles. Furthermore, pan-cancer and chemosensitivity analyses were conducted for deep exploration.
The results revealed that the eIF3a expression was higher in DLBCL than in healthy controls, correlating with worse prognosis. The protein expression of eIF3a was significantly elevated in DLBCL cell lines compared to PBMCs from healthy donors. Knockdown of eIF3a inhibited DLBCL cell proliferation and downregulated proliferation-related proteins while increasing cell apoptosis rate. Additionally, 114 DEGs associated with cell cycle and tumor immunity were identified.
Mutations in eIF3a and DEGs correlated with chemosensitivity and vital signaling pathways. Pan-cancer analysis revealed a correlation between high eIF3a expression and worse prognosis across various tumors. Furthermore, eIF3a expression was linked to chemosensitivity to specific anti-tumor drugs in DLBCL, including Vincristine and Wee1 inhibitors.
The study concluded that the high expression of eIF3a in DLBCL and its prognostic significance suggest a potential role in promoting disease development by regulating cell proliferation and apoptosis.
Furthermore, the observed correlation between eIF3a expression and immune profile and chemosensitivity in DLBCL highlights its multifaceted involvement in disease progression. These findings underscore the potential of eIF3a as both a prognostic biomarker and a therapeutic target for DLBCL.
This study was sponsored by the National Natural Science Foundation; Key Research and Development Program of Shandong Province; Taishan Scholars Program of Shandong Province; Translational Research Grant of NCRCH; Shandong Provincial Engineering Research Center of Lymphoma; Academic Promotion Programme of Shandong First Medical University; China Postdoctoral Science Foundation; Shandong Provincial Natural Science Foundation.
Source: https://pubmed.ncbi.nlm.nih.gov/38589831/
Sun H, Shang J, Liu X, et al. (2024). “Eukaryotic initiation factor 3a promotes the development of diffuse large B-cell lymphoma through regulating cell proliferation.” BMC Cancer. 2024 Apr 8;24(1):432. doi: 10.1186/s12885-024-12166-0. PMID: 38589831; PMCID: PMC11003032.
