Aug 2026· Frontiers in Oncology· Vol 16· 0 citations· 49 references
Medicine
TL;DR
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.
Abstract
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.
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
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.
Qi Li, Sheng-Ke Wen, Hong Chen et al.· Current Cancer Therapy Revie...· 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
CCHC zinc finger protein 10 (ZCCHC10) has been implicated in the progression of multiple malignancies, but its prognostic value and role in immune infiltration in breast cancer remain unclear. In this study, we systematically analyzed ZCCHC10 expression using public databases and validated the findings by immunohistochemistry. Associations with clinicopathological features and patient prognosis were assessed, and a prognostic nomogram was constructed. Co-expression networks and gene set enrichment analysis were used to explore functional pathways, while immune infiltration was evaluated and potential therapeutic agents were predicted. Functional assays, including proliferation and colony formation experiments, were performed to examine the biological role of ZCCHC10 in vitro. Our results demonstrated that ZCCHC10 was significantly upregulated in breast cancer and associated with poor prognosis and adverse clinicopathological characteristics. Enrichment analysis indicated involvement in immune-related pathways, and its expression correlated with immune cell infiltration and immunomodulators. Drug sensitivity prediction suggested Ipatasertib as a candidate targeted therapy requiring experimental verification. Knockdown of ZCCHC10 markedly inhibited breast cancer cell proliferation. Collectively, these findings suggest that ZCCHC10 serves as a prognostic biomarker and a key regulator of immune infiltration in breast cancer.
Miao Chen, Si-Qi Wang, Xiang Li et al.· Scientific Reports· 0 citations
Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with limited reliable biomarkers for early diagnosis and prognosis. In this study, we explored the role of DCUN1D5, a potential biomarker, in HCC. Methods We performed integrated bioinformatics analyses of publicly available HCC datasets, including TCGA, GEO, and ICGC, followed by in vitro experiments on HCC cell lines to validate our findings. Results DCUN1D5 expression was significantly elevated in HCC tissues compared to normal liver tissues. High DCUN1D5 levels were associated with poor prognosis and advanced tumor stage in HCC patients. Additionally, bioinformatics analysis revealed a correlation between DCUN1D5 expression levels and both immune infiltration and immunotherapy response in hepatocellular carcinoma. Functional assays revealed that DCUN1D5 knockdown inhibited cell proliferation, migration, and invasion in HCC cells. Mechanistically, Enrichment analysis revealed significant correlations between DCUN1D5 and multiple biological pathways; specifically, we observed a negative correlation between the expression level of DCUN1D5 and fatty acid metabolism. Further cellular experiments demonstrated that knockdown of DCUN1D5 can induce accumulation of free fatty acids in hepatocellular carcinoma cells. Conclusion In summary, our study identified DCUN1D5 as a potential biomarker for poor prognosis in HCC, high expression of DCUN1D5 are closely associated with tumor invasion and proliferation. Knockdown of DCUN1D5 was found to inhibit the proliferation, migration, and invasion of HCC cells and increases its free fatty acid accumulation. These studies suggest new possibilities for treatment strategies for HCC.
Tong Wang, Tian-Run Yang, Tian-Ze Wang et al.· Journal of Hepatocellular Ca...· 0 citations
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