IFFO2 Promotes Tumor Progression and Serves as a Prognostic Biomarker in Liver Hepatocellular Carcinoma
Qi Li, Sheng Ke Wen, Hong Chen, Wenhua Shi, Liji Li, Bing Wang, Peiliang Shi, Min Qiu, Wei ZhaoIntroduction:
To investigate the role of Intermediate Filament Family Orphan Protein 2 (IFFO2) in Liver Hepatocellular Carcinoma (LIHC), we systematically evaluated mRNA expression and analyzed the correlation between IFFO2 expression and clinicopathological information, patient prognosis, and the immune microenvironment. In this study, the influence of IFFO2 on LIHC proliferation, clone formation, migration, and invasion was demonstrated using in vitro experiments. This will provide a theoretical basis for IFFO2 to be developed into a biomarker and therapeutic target for LIHC.
Materials and Methods:
IFFO2 expression in pan-cancer and LIHC tissues was analyzed in the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. For assessing diagnostic value, Receiver Operating Characteristic (ROC) curves were used, and Kaplan-Meier (KM) and Cox regression were used for Prognostic analysis. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to examine the relationship between IFFO2 expression and immune cell infiltration. In vitro experiments used siRNA to knock down IFFO2 in HUH7 and HepG2 cells, followed by CCK-8 proliferation assays, clone formation, scratch wound-healing assays, transwell invasion assays, and other experiments to examine changes in cellular behavior.
Results:
IFFO2 expression was obviously upregulated in the LIHC tissues (p < 0.05). The results of the ROC analysis showed a high diagnostic ability, with an Area Under the Curve (AUC) of 0.790. Increased IFFO2 is associated with high pathological stages, high levels of Alpha-Fetoprotein (AFP), prolonged prothrombin time, and shortened overall survival (OS) (p < 0.05). Functional enrichment analysis revealed that IFFO2 is significantly associated with immune regulation, cell cycle, and complement activation pathways. Immune infiltration analysis demonstrated the presence of various immune cell subtypes that exhibited both positive and negative correlations with IFFO2. In vitro experiments have demonstrated that IFFO2 knockdown remarkably diminishes the proliferation, clone formation, migration, and invasion capacities of LIHC cells (p < 0.05).
Discussion:
The findings suggest that IFFO2 functions as an oncogene in LIHC. Its strong association with adverse prognosis and its potential to modulate the immune microenvironment underscore its dual potential as a diagnostic biomarker and a promising therapeutic target, warranting further mechanistic and clinical investigation.
Conclusion:
IFFO2 is significantly upregulated in LIHC and promotes tumor progression; its expression is associated with unfavorable prognostic outcomes, suggesting its potential utility as a biomarker for diagnosis and a therapeutic target.