Targetable genes associated with hematogenous metastasis in gastric cancer using the TCGA database

Identification of a metastasis-associated prognostic gene signature in osteosarcoma through integrated bioinformatics and functional analysis

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.

Transcriptome Dynamics From Primary Gastric Cancer to Peritoneal Metastases: Translational Insights for Surgical Oncology.

BACKGROUND AND AIMS Peritoneal metastases (PMs) represent the most frequent, clinically challenging dissemination pattern in advanced gastric cancer, especially poorly cohesive (PCGC) subtype, and are associated with poor prognosis. We aimed to characterize the transcriptomic landscape of primary gastric tumors (PGTs) and matched PMs to identify differential molecular programs, tumor-microenvironment (TME) features, and potential biomarkers. METHODS We analyzed 55 FFPE samples from 23 treatment-naïve patients with synchronous peritoneal-only stage IV PCGC and 10 non-neoplastic gastric controls (NNC). RNA sequencing was analyzed using DESeq2 and GSEA, with cell proportions estimated through immune deconvolution (TIMER/xCell). RESULTS A total of 4279 differentially expressed genes were identified across all groups. CLDN18 expression progressively decreased from NNCs to PGTs and PMs. Direct PGT-PM comparison revealed that PGTs were characterized by cytoskeletal and extracellular-matrix remodeling genes upregulation, mitotic/cell-cycle, NOTCH and apical-junction pathways enrichment, and memory T-cell predominance. Compared with PGTs, PMs showed increased IGF1, IGFN1, NTRK2 and adipogenesis-related transcripts, adipogenesis and MAPK7/11-NTRK2 signaling enrichment, and macrophage-dominant and dendritic-cell-dominant microenvironments. epithelial-mesenchymal transition (EMT), inflammatory pathways, and cancer-associated fibroblasts were shared by both tumor lesions. PMs did not match established TCGA or PCGC subtypes, suggesting a distinct molecular identity. CONCLUSIONS PMs are characterized by TME remodeling and transcriptional reprogramming. Shared EMT and inflammatory pathways act as bridge linking PGT to PM, consistent with adaptive exploitation of physiological peritoneal programs. Collectively, our findings suggest a transcriptomic framework in which PM can be characterized as a distinct niche-conditioned biological entity and support microenvironment-informed diagnostic and therapeutic strategies.

ZUP1 as a Novel Potential Oncogenic Driver and Prognostic Biomarker in Breast Cancer.

INTRODUCTION Breast cancer is one of the main causes of cancer death in women globally. Identifying new predictive markers and therapeutic targets is important for improving patient outcomes. Zinc finger-containing U-rich RNA-binding protein 1 (ZUP1) is an RNA-binding protein containing a zinc finger structure that has not been systematically analyzed in breast cancer research. MATERIALS AND METHODS The study used data from 1,231 samples from the Cancer Genome Atlas (TCGA) database. The ZUP1 expression in tumor tissues and normal tissues was compared. Its predictive value was assessed using survival analysis and regression models. Its biological role was explored through gene functional analysis. The immune cell analysis method was used to study the tumor immune environment, and the drug susceptibility database was used to predict drug responses. Predictive models were also built and validated. RESULTS ZUP1 expression was significantly higher in breast cancer tissues than in normal tissues. High expression of ZUP1 is related to advanced tumor stage and is an independent indicator of poor survival prognosis in univariate and multivariate analyses. Functional enrichment revealed that ZUP1 is closely linked to cell cycle progression, DNA replication, and the Fanconi anemia (FA) pathway. Immune infiltration analysis demonstrated a significant negative link between ZUP1 levels and the abundance of resting mast cells and activated NK cells. Furthermore, high ZUP1 expression was associated with increased sensitivity to several targeted therapies, including Nutlin-3a and PD-0325901. A clinically applicable nomogram combining ZUP1 expression with key clinical factors (age, stage, T, N, M) was developed to predict 3- and 5-year OS with good calibration and discrimination. DISCUSSION Our study identifies ZUP1 as a potential oncogenic factor and a robust independent prognostic biomarker in breast cancer. Its involvement in critical cellular processes and modulation of the tumor immune microenvironment highlights its potential as a novel therapeutic target. Functional experiments, including immunohistochemical staining and CCK8 proliferation assays, further supported the oncogenic role of ZUP1. The established nomogram provides a valuable tool for personalized risk assessment and clinical decision-making. CONCLUSION Our findings suggest that ZUP1 is a novel multifaceted biomarker with significant implications for personalized treatment strategies in breast cancer.

Downregulation of RGS2 Expression in Ovarian Cancer: A TCGA–GTEx Transcriptomic Analysis

Regulator of G protein signaling 2 (RGS2), a negative regulator of G protein-coupled receptor signaling, is implicated in ovarian cancer. Given the disease's late-stage diagnosis and poor prognosis, identifying reliable molecular biomarkers is crucial. This study evaluated RGS2 gene expression in ovarian cancer and its clinicopathological and prognostic associations using public transcriptomic data. RNA-sequencing data from 419 The Cancer Genome Atlas (TCGA) tumor samples and 88 Genotype-Tissue Expression (GTEx) normal samples were compared using the Mann-Whitney U test. Additionally, 308 TCGA cases were analyzed for associations with tumor grade, clinical stage, and survival outcomes—including overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease-free interval (DFI) using the Kaplan-Meier method and log-rank tests based on median RGS2 expression. Results demonstrated that RGS2 was significantly down-regulated in ovarian cancer tissues compared to normal tissues (p<0,001). However, RGS2 expression showed no significant correlation with tumor grade, clinical stage, or any evaluated survival metrics (all p>0,05). In conclusion, while RGS2 is consistently down-regulated at the transcript level in ovarian cancer, it is not significantly associated with patient survival. These findings suggest that although reduced RGS2 expression is a common molecular feature of ovarian cancer, its utility as a standalone prognostic biomarker is limited in unstratified transcriptomic analyses.

Seven-Gene Signature and Immune Microenvironment as Determinants of Survival Rate in Colorectal Carcinoma

A seven-gene immune-related prognostic signature that, combined with clinicopathological parameters, provides a robust tool for individualized survival prediction and may guide precision management in CRC patients is developed and validated.