FBXW8 is upregulated in hepatocellular carcinoma and promotes HCC cell malignancy.

DBF4B promotes hepatocellular carcinoma progression by regulating CCNA2 and PSMD11 expression

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by unfavorable clinical outcomes. Identifying novel biomarkers and therapeutic targets is essential for advancing HCC management. Although DBF4 zinc finger B (DBF4B) has been associated with the progression of various cancers, its specific role in HCC remains poorly understood. The expression pattern of DBF4B in HCC tissues was analyzed using the Gene Expression Omnibus (GEO) database. Prognostic analysis was performed using The Cancer Genome Atlas (TCGA) database, and the prognostic value of DBF4B was evaluated through Kaplan-Meier survival analysis and nomogram construction. Subsequently, the expression level and prognostic significance of DBF4B were validated using clinical tissue microarray (TMA) samples. In vitro functional experiments were conducted to investigate the effects of DBF4B knockdown on HCC cell proliferation and migration. Bioinformatics enrichment analysis, qRT-PCR and Western blotting were employed to explore the downstream molecular mechanisms of DBF4B. Rescue experiments were performed to validate the downstream mechanism, and a subcutaneous xenograft model in nude mice was established to evaluate the impact of DBF4B silencing on tumor growth. DBF4B expression was upregulated in HCC tissues and cell lines. High DBF4B expression was closely associated with shorter overall survival (OS) and progression-free survival (PFS) in HCC patients, and served as an independent prognostic factor. Functional experiments demonstrated that silencing DBF4B markedly suppressed the proliferative and migratory capabilities of HCC cells. Mechanistically, DBF4B positively regulated the expression of cyclin A2 (CCNA2) and proteasome 26 S subunit non-ATPase 11 (PSMD11), which are key regulators of cell cycle progression. Of these two molecules, CCNA2 was prioritized for subsequent functional rescue studies. Overexpression of CCNA2 effectively restored the proliferative and migratory capacities impaired by DBF4B silencing. Moreover, in vivo xenograft models showed that DBF4B silencing substantially inhibited tumor growth, as reflected by diminished tumor volume and weight, along with downregulation of the proliferation marker Ki67. DBF4B acts as an oncogene in HCC by promoting cell proliferation and migration through regulating CCNA2 and PSMD11 expression. Thus, it holds promise as both a prognostic biomarker and a novel therapeutic target for HCC.

High Expression of SAMM50 Indicates Poor Clinical Prognosis in Hepatocellular Carcinoma and Represents a Potential Novel Biomarker.

Identifying diagnostic and prognostic biomarkers and therapeutic targets for hepatocellular carcinoma (HCC) is essential to improve risk stratification, guide individualized treatment, and enhance therapeutic efficacy.The expression of SAMM50 (Sorting and Assembly Machinery Component 50) was initially analyzed in publicly accessible curated genomic and proteomic databases, such as the Cancer Cell Line Encyclopedia, the Human Protein Atlas, and other HCC-specific repositories. This analysis revealed differential expression patterns between HCC and non-neoplastic liver tissue. Subsequently, clinicopathological data and tissue specimens were collected from 200 HCC patients who underwent treatment at our institution. The protein and transcript levels of SAMM50 were experimentally measured in paired HCC and adjacent non-tumorous tissues using immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The association between SAMM50 expression and key clinicopathological features was further evaluated. Univariate and multivariate Cox proportional hazards analyses were performed to determine the independent prognostic value of SAMM50 expression in HCC. Based on these results, a reproducible and clinically applicable nomogram, supported by a forest plot, was constructed to facilitate prognostic prediction and support individualized therapeutic decision-making. Finally, in vitro and in vivo experiments were conducted to characterize the phenotypic alterations in HCC cells after SAMM50 knockdown, thereby confirming its involvement in critical oncogenic behaviors.This research demonstrated that the mRNA and protein levels of SAMM50 in HCC tissues were elevated compared to those in normal liver and adjacent tissues. Immunohistochemistry findings confirmed that SAMM50 protein levels were persistently higher in HCC tissues than in paired adjacent tissues. High expression of SAMM50 was correlated with unfavorable clinicopathological factors, encompassing pretreatment alpha-fetoprotein (AFP) levels, tumor size, T stage, American Joint Committee on Cancer (AJCC) stage, histological grade, and worse overall survival.Specifically, high expression of SAMM50 was linked to shorter overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Moreover, univariate and multivariate Cox analyses were conducted to investigate the association between SAMM50 expression and clinicopathological features in HCC patients and to identify independent prognostic factors. The area under the receiver operating characteristic (ROC) curve (AUC) for SAMM50 was 0.863, suggesting its potential as a diagnostic marker for HCC, though further validation in independent cohorts is needed. Silencing of SAMM50 inhibited HCC cell proliferation, migration, and invasion, promoted apoptosis in vitro, and suppressed HCC growth in vivo.This research demonstrates that SAMM50 shows potential diagnostic value for HCC, though this observation requires further validation in larger, independent, and prospective cohorts. The results of this study not only contribute to the evaluation of baseline data and risk stratification in HCC but also offer novel approaches for the development of precise treatment strategies and targeted therapies.

STARD3NL as a prognostic marker related to an immunosuppressive tumor microenvironment in hepatocellular carcinoma

Background Changes in the tumor microenvironment (TME) are closely involved in hepatocellular carcinoma (HCC) development, and lipid metabolic disorders may take part in this process. STARD3NL is known to be related to cholesterol trafficking and lipid homeostasis. However, little is known about whether STARD3NL is linked to immune features of the HCC microenvironment. Methods We first explored STARD3NL expression and its prognostic relevance in HCC using The Cancer Genome Atlas (TCGA). To verify the bioinformatic findings, HCC tissue microarrays (TMAs) were analyzed by immunohistochemistry (IHC) for STARD3NL localization and survival evaluation. Multiplex immunohistochemistry (mIHC), combined with digital image analysis, was further used to characterize immune cell infiltration. Clinicopathological differences between tumors with high and low STARD3NL expression were also examined. In addition, spatial distance analysis was performed to assess how immune cells were arranged in STARD3NL-high regions. Results TCGA-based analysis and mIHC validation both showed higher STARD3NL expression in HCC tissues. Patients with increased STARD3NL expression had poorer survival (p = 0.029), and multivariable analysis supported STARD3NL as an independent risk factor. STARD3NL-high tumors showed increased proportions of CD68+ macrophages and FOXP3+ T cells (p < 0.005). Spatial analysis further indicated that Tregs were more frequently located near macrophages (p = 0.001), with a shorter mean macrophage-Treg distance (p = 0.027). This macrophage-Treg proximity was associated with worse prognosis (p = 0.030). Conclusion High STARD3NL expression is significantly associated with immune-suppressive features and unfavorable outcomes in HCC. These findings indicate that STARD3NL may have value as a prognostic biomarker associated with an immunosuppressive tumor microenvironment.

C17orf75 (Njmu-R1) promotes hepatocellular carcinoma progression: a pan-cancer analysis and experimental validation

Background Chromosome 17 Open Reading Frame 75 (C17orf75) encodes the protein Njmu-R1 (Protein Njmu-R1),, which is involved in intracellular vesicle trafficking; however, its role in tumor progression remains largely unclear. Methods Public datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were analyzed to evaluate the expression profile, mutation landscape, and diagnostic and prognostic value of C17orf75. Bioinformatics analyses were subsequently performed to explore its associations with immune infiltration. In addition, functional assays were conducted on Hep3B and MHCC-97H cells, and immunohistochemistry (IHC) was performed on clinical liver hepatocellular carcinoma (LIHC) samples. Results C17orf75 was significantly upregulated in multiple cancer types, particularly in LIHC. Elevated C17orf75 expression was associated with unfavorable prognosis and advanced clinicopathological features in LIHC. Functional enrichment analyses indicated that C17orf75-related genes were involved in cell cycle regulation, DNA replication, and epithelial–mesenchymal transition (EMT). Furthermore, C17orf75 expression was closely correlated with immune infiltration, ferroptosis-related genes, and m6A regulators. Knockdown of C17orf75 inhibited the proliferation, migration, and invasion of LIHC cells. C17orf75 knockdown induced G2-phase arrest without significantly affecting apoptosis. Moreover, knockdown of C17orf75 suppressed EMT. Conclusion C17orf75 plays an important role in LIHC progression by regulating cell cycle progression and EMT, and it may serve as a potential therapeutic target for LIHC.

High expression of FBLIM1 as a potential biomarker for early detection of HNSCC tumorigenesis and predicts poor survival.

IFFO2 Promotes Tumor Progression and Serves as a Prognostic Biomarker in Liver Hepatocellular Carcinoma

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.