ERP44 Is Associated With Poor Prognosis and Promotes Proliferation and Temozolomide Resistance in Lower-grade Glioma

ULBP1 is a prognostic biomarker associated with immune suppression in breast cancer

ULBP1 may serve as a potential novel prognostic biomarker in BC, and targeting ULBP1 may provide a new therapeutic strategy for BC.

TPI1 promotes malignant progression and ferroptosis resistance in head and neck squamous cell carcinoma

This study identifies TPI1 as a key tumor-promoting factor and independent prognostic biomarker in HNSCC, providing a promising therapeutic target for overcoming ferroptosis evasion in HNSCC.

Prognostic Value of VPS45 in HCC and Its Correlation with Immune Microenvironment

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.

Prognostic value of FUBP1 in Colorectal cancer and association with immune microenvironment characteristics.

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.

Unraveling the pro-oncogenic role of GLIPR2: Its molecular basis in glioma malignancy.

Adult diffuse gliomas remain challenging to treat because of their infiltrative growth and resistance to multimodal therapy. Although GLIPR2 has been implicated in autophagy regulation and tumor-related processes, its role in glioma remains unclear. In this study, transcriptomic and clinical data from TCGA, CGGA, and GTEx were integrated with western blotting and immunohistochemical validation in human glioma specimens. Prognostic significance was evaluated using Kaplan-Meier and ROC analyses. Functional effects of GLIPR2 knockdown were examined in U138 and U251 glioma cells through assays of proliferation, migration, invasion, apoptosis, DNA damage, and clonogenic survival. KEGG enrichment analysis and western blotting were used to investigate associated signaling pathways. GLIPR2 expression was significantly elevated in gliomas, predominantly localized in the cytoplasm, and positively correlated with tumor grade. High GLIPR2 expression was associated with unfavorable overall survival and demonstrated predictive value for 1-, 3-, and 5-year survival. Silencing GLIPR2 inhibited glioma cell proliferation, migration, and invasion while promoting apoptosis. Moreover, GLIPR2 knockdown enhanced irradiation-induced γ-H2AX accumulation and reduced post-irradiation clonogenic survival, indicating impaired resolution of radiation-induced DNA damage and increased radiosensitivity. Mechanistically, GLIPR2 depletion was accompanied by reduced PI3K/AKT pathway activity and lower p-GSK-3β and MMP9 expression, without altering total GSK-3β levels. These findings identify GLIPR2 as a glioma-associated biomarker linked to malignant progression, unfavorable prognosis, and radioresistance and nominate it as an investigational molecular vulnerability for further validation.

Assessing the significance of CCNE1 overexpression in triple negative breast cancer.