Background: Emerging evidence suggests that beta-blockers (BBs) may influence cancer progression by modulating the neuroimmune axis. However, clinical findings remain heterogeneous, necessitating a comprehensive evaluation of their impact on survival outcomes and immune modulation across malignancies.Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines, analyzing 79 studies from PubMed, Embase, and Web of Science. Pooled hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) were calculated using random-effects models. Subgroup analyses explored effects by cancer type, BB class (non-selective vs. β1-selective), and concurrent immunotherapy. Immune biomarkers (e.g., PD-L1 expression, tumor-infiltrating lymphocytes) were qualitatively synthesized.Results: BB use showed no significant overall effect on CSS (HR = 0.97, 95% CI: 0.92–1.02) but exhibited substantial heterogeneity (I² = 80%). Protective associations were observed in breast cancer (HR = 0.27–0.50) and melanoma, while detrimental effects emerged in pancreatic and head/neck cancers (HR > 1.0). Clinically, BBs combined with immune checkpoint inhibitors (ICIs) improved survival (HR=0.91, 95% CI: 0.85–0.98), particularly in PD-L1+ tumors (OR=1.29 for enhanced expression). Non-selective BBs showed stronger immune modulation (CD8+ T-cell SMD=0.49 vs 0.22 for β1-selective).Conclusion: BBs demonstrate clinically meaningful benefits when combined with immunotherapy (HR=0.91) particularly in β2-AR+ melanoma and breast cancer, but show potential harm in pancreatic/head-neck cancers (HR>1.0). These results support preferential use of propranolol (20-40mg/day) in immunotherapy-treated melanoma, and avoidance of routine BB use in non-immunogenic tumors without adrenergic profiling. Prospective trials should validate these selection criteria.

Background: Long non-coding RNAs (lncRNAs) have been implicated in diagnosis and prognosis in various cancers. However, few lncRNA signatures have been established for prediction of gastrointestinal stromal tumors (GIST). We aimed to explore a lncRNA signature profile that associated with clinical relevance by mining data from Gene Expression Ominus (GEO) and Surveillance, Epidemiology, and End Results (SEER) Program. Methods: Using a lncRNA-mining approach, we performed non-negative matrix factorization (NMF) consensus algorithm in Gastrointestinal stromal tumors (GISTs) cohorts (61 patients from GSE8167 and GSE17743) to cluster LncRNA expression profiles. Comparative markers selection, and Gene Set Enrichment Analysis (GSEA) algorithm were performed between distinct molecular subtypes of GIST. The survival rate of GIST patients from SEER stratified by gender were compared by Kaplan–Meier method and log-rank analysis. lncRNA-mRNA co-expression analysis was performed by Pearson correlation coefficients (PCC) using R package LINC. Somatic copy number alterations of GIST patients (GSE40966) were analyzed via web server GenePattern GISTIC2 algorithm. Results: A total of four lncRNA molecular subtypes of GIST were identified with distinct biological pathways and clinical characteristics. LncRNA expression profiles well clustered the GIST samples into small size (5 mm), which is a fundamental index for GIST malignancy diagnosis. Several lncRNAs with abundant expression (LRRC75A-AS1, HYMAI, NEAT1, XIST and FTX) were closely associated with tumor size, which may suggest to be biomarkers for the GIST malignancy. Particularly, LRRC75A-AS1 was positively associated with tumor diameters and suggested an oncogene in GIST. Co-expression analysis suggested that chromosome region 17p11.2–p12 may contribute to the oncogenic process in malignant GIST. Interestingly, the gender had a strong influence on clustering by lncRNA expression profile. Data from the Surveillance, Epidemiology, and End Results (SEER) Program were further explored and 7983 patients who were diagnosed with GISTs from 1973 to 2014 were enrolled for analysis. The results also showed the favorable prognosis for female patients. The survival rate between male and female with GIST was statistically significant (P < 0.0001). Gene set enrichment analysis (GSEA) indicated distinct pathways between female and male, and malignant GIST was associated with several cancer metabolism and cell cycle associated pathways. Conclusions: This lncRNAs-based classification for GISTs may provide a molecular classification applicable to individual GIST that has implications to influence lncRNA markers selection and prediction of tumor progression.

Background and Aim: n-3 PUFAs have been shown to have multiple biological effects on cancers. The fat-1 gene encodes an n-3 desaturase that introduces a double bond at the n-3 position of the hydrocarbon chain in n-6 fatty acids to form an n-3 fatty acid. Here we investigated the anti-tumorigenesis effect of Fat-1 gene. Methods: Mounting evidence indicates that activation of AKT and Ras pathways is a key oncogenic event in human hepatocarcinogenesis. Our previous results demonstrate that co-expression of AKT and N-Ras in the mouse liver promotes rapid hepatocarcinogenesis in vivo. Here we utilized hydrodynamic tail vein injection of Fat-1 gene to AKT/Ras hepatocarcinogenesis' model to testify its anti-tumorigenesis effect. Results: Hydrodynamic injection of Fat-1 gene could inhibit lipogenesis and affects liver tumor development in co-expressing AKT and Ras oncogenes' mice. Molecular analysis showed that Fat-1 gene strongly inhibited the Ras/MAPK and Akt/ mTORC cell signal pathway, and significantly inhibited de novo lipogenesis by inhibition of fatty acid biosynthesis gene (FASN, ACLY) and transcription factors (LXR-β, SREBP1), which were highly elevated in AKT/Ras mice. The AKT/Ras cells lines in vitro also showed the similar results. Noticeably, although the hydrodynamic injection of fat-1 gene showed significant inhibition effect of hepatocarcinogenesis, it didn't change fatty acid profile in various tissues of mice, which is different from previous studies by using Fat-1 transgenic mice. Conclusions Local expression of Fat-1 gene can achieve sufficient suppression of AKT/Ras-induced hepatocarcinogenesis. Thus, with multiple biological effects on various signal pathways, Fat-1 gene can prevent of hepatocarcinogenesis.