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, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Colon adenocarcinoma (COAD) is a malignancy with high mortality rate and complex biological characteristics heterogeneity, which poses challenges for clinical treatment. Anoikis type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), it plays crucial role in tumor metastasis. However, specific link between anoikis COAD, as well its mechanisms progression, remains unclear, making potential new direction therapeutic strategy research. We employed transcriptomic data information from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) pinpoint differentially expressed anoikis-related genes (ARGs) COAD. Using Cox proportional hazards models Lasso regression analysis, we developed prognostic signature derived these ARGs. also investigated roles interactions microenvironment by analyzing single-cell RNA sequencing data. Additionally, molecular docking techniques evaluate inhibin subunit beta B (INHBB) targets assess binding affinity candidate drugs. Finally, used gene knockout silence key INHBB explored functions vitro. In our study, expression differences ARGs, successfully classified patients Kaplan-Meier survival analysis demonstrated elevated risk scores experienced poorer prognosis, finding was confirmed both training validation cohorts. immune infiltration revealed notable increase presence within high-risk patients. Molecular identified drug candidates INHBB, including risperidone. Furthermore, vitro experiments showed downregulation COAD lines significantly reduced cellular viability migration capacity. summary, research, based on provides insights into precise classification, prognosis assessment, identification It validates progression establishing foundation future personalized treatment strategies.

Language: Английский

Identification of new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from LDHC in lung adenocarcinoma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Background Lactate dehydrogenase C (LDHC) is a kind of cancer-testis antigen (CTA) that has been reported to be biomarker for diagnosis, efficacy evaluation, and recurrence monitoring lung adenocarcinoma (LUAD). This study aims assess the value LDHC in peptide-based vaccines LUAD immunotherapy. Methods The recombinant protein was purified its effect on PC9 cells evaluated by wound healing assay, Transwell invasion, migration assay. Ten HLA-A2-restricted LDHC-derived peptides were predicted synthesized, affinity HLA-A2 molecule analyzed T2 binding assay docking. Enzyme-linked immunospot (ELISpot) LDH cytotoxicity performed determine interferon-γ (IFN-γ) release level tumor cell lysis ability peptide-induced specific cytotoxic T lymphocytes (CTLs). Results promoted invasion cells. Three P2 (LDHC 170–180 , FRYLIGEKLGV), P5 116–124 IMKSIIPAI), P6 172–180 YLIGEKLGV) had high at 50 μg/mL. elicited strongest IFN-γ-secreting lymphocyte (CTL) response exhibited potent against HLA-A2-positive with expression. Conclusions may serve as targetable immunotherapy LUAD.

Language: Английский