ArticleJournal of translational medicine2024
FANCA promotes lung adenocarcinoma progression and is a potential target for epitope vaccine immunotherapy.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Effect of antiserum against recombinant EGr_09888 on the in vitro development of Echinococcus granulosus protoscoleces.Parasitology research · 2025Article
- Identification of new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from LDHC in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target.Frontiers in immunology · 2024Article
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Abstract
backgroundFANCA mutations have been detected in a variety of cancers and found to be pro-carcinogenic. However, no functional studies have been identified regarding the involvement of FANCA in the occurrence and the immune response of LUAD.
methodsThe mRNA expression and overall survival rates of FANCA were evaluated by the TIMER, PrognoScan and TCGA database in LUAD tissues, and FANCA expression was further validated by clinical serum samples using ELISA. The correlation between FANCA and immune infiltration level was investigated via TISIDB database and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of FANCA in related immune cells. Then, the influence of FANCA knockout on the proliferation, migration, and invasion of A549 and H1299 cells was validated using CCK8, cloning formation, and Transwell assays. Subsequently, HLA-A2-restricted FANCA antigenic peptides were predicted and synthesized by NetMHC4.0 and SYFPEITHI, and DCs were induced and cultured in vitro. Finally, DCs loaded with HLA-A2-restricted FANCA antigenic peptides were co-cultured with autologous peripheral blood lymphocyte to generate specific CTLs. The killing effects of different CTLs on LUAD cells were studied.
resultsThe results showed that high levels of FANCA in patients with LUAD were significantly correlated with worse OS survival, which was correlated with age, clinical stage, pathological T stage, M stage, and N stage in LUAD. Knockdown of FANCA in A549 and H1299 cells significantly inhibited proliferation, metastasis, and invasion in vitro. In addition, FANCA was significantly related to immune infiltrate, genomic alterations and TMB. FANCA expression infuenced the prognosis of LUAD patients by directly affecting immune cell infltration. Finally, HLA-A2-restricted FANCA antigenic peptides were synthesized. And FANCA 146-154 (SLLEFAQYL) antigenic peptide exhibit a stronger affinity for DCs, and induce CTLs to produce stronger targeted killing ability for LUAD cells at an effector-to-target ratio of 40:1.
conclusionThese results demonstrated that the elevation of FANCA promotes malignant phenotype of LUAD, and the potential peptide P2 (SLLEFAQYL) derived from FANCA may be used as an epitope vaccine for the treatment of LUAD.
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