Jul 2026· Current Cancer Therapy Reviews· 0 citations
TL;DR
Functional enrichment analysis revealed that IFFO2 is significantly associated with immune regulation, cell cycle, and complement activation pathways, and 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.
Abstract
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.
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.
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).
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.
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.
OBJECTIVE
To investigate FUBP1 expression, its prognostic value, impact on the tumor microenvironment (TME), and drug sensitivity in colorectal cancer (CRC), and to explore its potential underlying mechanisms.
METHODS
Using data from The Cancer Genome Atlas (TCGA), we analyzed FUBP1 expression in CRC, evaluated its prognostic value via survival analysis and nomogram construction, performed pathway enrichment analysis, and assessed immune cell infiltration and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores. We further conducted immunohistochemistry (IHC) validation on an independent institutional cohort and analyzed the Gene Expression Omnibus (GEO) single-cell RNA sequencing dataset GSE132465 (n = 63,689 cells) to examine the association between FUBP1 expression and the tumor immune microenvironment at single-cell resolution.
RESULTS
FUBP1 was highly expressed in CRC (P < 0.001), particularly in younger patients. High FUBP1 expression was associated with improved overall survival in univariate analysis (HR = 0.68, P = 0.028), yet this association was not maintained as an independent prognostic factor after adjustment for other clinical covariates (HR = 0.722, P = 0.098). Immunohistochemistry results from the independent cohort confirmed upregulated FUBP1 protein in 90% of CRC specimens. Single-cell analysis revealed that FUBP1-high cell clusters exhibited markedly reduced immune cell infiltration (35.97%vs 62.96%, P < 0.001), indicating an immunosuppressive "cold" tumor microenvironment. Tumors with high FUBP1 expression also displayed elevated PD-L1, PD-1, and CTLA4 expression, lower half-maximal inhibitory concentration (IC50) values for oxaliplatin, irinotecan, and 5-fluorouracil, and higher Immune Phenotype Score (IPS) for anti-PD-1 monotherapy or combined anti-CTLA-4 immunotherapy. FUBP1 expression was correlated with increased expression of MYC, TP53, and their downstream target genes (CCND1, CDK4, BAX, CDKN1A).
CONCLUSION
FUBP1 is highly expressed in CRC and associated with an immunosuppressive "cold" tumor microenvironment characterized by decreased immune cell infiltration, while it correlates with favorable chemotherapeutic sensitivity. FUBP1 may serve as a potential predictive biomarker for responses to chemotherapy and immunotherapy, rather than an independent prognostic indicator for survival. Its linkage to MYC and TP53 signaling pathways warrants further mechanistic investigation.
Zhen-Xiang Li, Yan-Fang Zhao, Yan-Li Si et al.· Cancer Treatment and Researc...· 0 citations
Purpose A growing body of research indicates that Vacuolar Protein Sorting 45 (VPS45) is essential for the development of tumours and the advancement of cancer. Its biological role and expression profile in HCC are still mostly unknown, nevertheless. Materials and Methods Using a variety of datasets, including the Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), among others, we examined the existence and prognostic importance of VPS45. Functional enrichment analysis was employed to elucidate the potential mechanisms through which VPS45 may influence HCC. Additionally, we assessed the relationship between VPS45 expression and immune cell infiltration using single-sample gene set enrichment analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumour tissues using Expression data (ESTIMATE). The Tumor Immune Dysfunction and Rejection (TIDE) algorithm was leveraged to assess the sensitivity of predicted gene expression to immunotherapy. Utilizing assays including CCK-8, wound healing, and Transwell migration and invasion methods, we performed in vitro experiments on the MHCC-97H cell line to further investigate the biological significance of VPS45 in the progression of hepatocellular carcinoma (HCC). Results According to our research, VPS45 expression is markedly elevated in HCC, and elevated VPS45 levels are associated with a worse prognosis for patients. Functional enrichment analysis showed that elevated VPS45 expression is closely linked to the activation of various oncogenic pathways. VPS45 silencing decreases HCC cell invasion, metastasis, and proliferation, according to in vitro investigations. Interestingly, it was shown that VPS45 levels showed a positive link with immunosuppressive cell populations and related genes, but a negative correlation with a number of anti-tumor immune cell types. Immunotherapy resistance is more common in patients with increased VPS45 expression. Conclusion This study clarifies the biological role of VPS45 in hepatocellular carcinoma (HCC) and, through comprehensive database analyses combined with in vitro experiments, supports its potential as a diagnostic and predictive biomarker for HCC. In addition to its value for disease detection and prognosis, VPS45 may help predict patient response to immunotherapy.
Ji-Ming Duan, Wen-Jun Zhao, Na Lv et al.· Journal of Hepatocellular Ca...· 0 citations
DBF4B holds promise as both a prognostic biomarker and a novel therapeutic target for HCC after functional experiments demonstrated that silencing DBF4B markedly suppressed the proliferative and migratory capabilities of HCC cells.
Bing Dong, Pengju Xi, Guang-Xin Yang et al.· Molecular Biology Reports· 0 citations
BACKGROUND
Lung adenocarcinoma (LUAD) is a predominant and lethal subtype of non-small cell lung cancer, with a lack of reliable prognostic biomarkers to guide clinical management. Basigin (BSG) has been implicated in tumor progression across multiple cancers, yet its expression pattern, prognostic significance, and underlying mechanisms in LUAD remain incompletely elucidated.
METHODS
We integrated multi-omics data from TCGA, GTEx, CCLE, and GEO databases to analyze BSG expression profiles. Clinical correlations were assessed via Kruskal-Wallis tests. Prognostic value was determined using Kaplan-Meier survival analysis, univariate/multivariate Cox regression, and nomogram construction with calibration curves. Functional enrichment (GO/KEGG) and immune infiltration analyses were performed to explore BSG-related mechanisms, followed by immunohistochemical (IHC) validation in A549 cells and clinical LUAD tissue microarrays.
RESULTS
BSG was significantly upregulated in LUAD tissues versus normal/paired adjacent tissues, correlating with advanced T/N/pathologic stages. High BSG expression predicted worse survival outcomes in TCGA-LUAD, which was validated in GEO datasets. Multivariate Cox regression identified BSG as an independent prognostic factor, with a well-calibrated nomogram for survival prediction. Functional exploration indicated that BSG mainly participated in tumor-associated and immunological pathways. Immune infiltration analysis indicated that BSG was significantly correlated with the infiltration of various immune cells. Moreover, BSG exhibited a strong association with immune checkpoint proteins, chemokines, chemokine receptors, and MHC genes. IHC further confirmed its cytoplasmic/membranous localization and prognostic relevance.
CONCLUSION
BSG serves as an independent prognostic biomarker and potential therapeutic target in LUAD, shedding light on its regulatory roles in tumor progression and immune microenvironment remodeling.
It is indicated that STARD3NL may have value as a prognostic biomarker associated with an immunosuppressive tumor microenvironment and patients with increased STARD3NL expression had poorer survival and multivariable analysis supported STARD3NL as an independent risk factor.
Di Li, Zi-Yu Liu, Lihe Xie et al.· Frontiers in Oncology· 0 citations
