👤 Qijun Wo

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with challenges in diagnosis and treatment due to tumor heterogeneity. This study identifies palmitoylation-related signature genes as potential diagnostic and therapeutic targets. Integrating GEO datasets, six differentially expressed genes (DEGs) linked to palmitoylation were identified. Machine learning algorithms (LASSO, RF, SVM) selected three core genes: TRPM4, LAMB3, and APOE. A diagnostic model based on these genes achieved an AUC of 0.929, demonstrating robust accuracy in distinguishing PCa from normal tissues. Functional analysis revealed roles in lipid metabolism and immune modulation, with ssGSEA highlighting correlations between key genes and immune cell infiltration. Experimental validation showed that LAMB3 overexpression suppressed PCa cell proliferation, migration, and invasion, while knockdown enhanced these processes. Molecular docking identified diethylstilbestrol as a potential therapeutic agent targeting LAMB3 and APOE. These findings emphasize the clinical relevance of palmitoylation-related genes in PCa diagnosis and therapy, offering novel biomarkers and insights for personalized treatment strategies. Show less

Extracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency. This paper introduces an optimized magnetic bead reagent, LipoMin, functionalized with glycosaminoglycans (GAGs), as a rapid alternative for LP removal during the second-step process in about 10 minutes. We evaluated LipoMin's efficacy on two sample types: (a) EV fractions isolated by size exclusion chromatography (SEC + LipoMin) and (b) the pellet obtained from ultracentrifugation (UC + LipoMin). The workflow is remarkably simple, involving a 10 min incubation with LipoMin followed by magnetic separation of the LP-depleted EV-containing supernatant. Results from enzyme-linked immunosorbent assay (ELISA) revealed that LipoMin removes 98.2% ApoB from SEC EV fractions, comparable to the LP removal ability of DG in the SEC + DG two-step process. Importantly, the EV yield (CD81 ELISA) remained at 93.0% and Western blot analysis confirmed that key EV markers, flotillin and CD81, were not compromised. Recombinant EV (rEV), an EV reference standard, was spiked into SEC EV fractions and recovered 89% of CD81 protein. For UC + LipoMin, ApoA1 decreased by 76.5% while retaining 90.7% of CD81. Notably, both colorectal cancer (CRC) and Alzheimer's disease (AD) samples processed by SEC + LipoMin and UC + LipoMin displayed clear expression of relevant EV and clinical markers. With a 10 min workflow (resulting in a 96% time saving compared to the traditional method), the LipoMin reagent offers a rapid and efficient alternative to DG for LP depletion, paving the way for a streamlined SEC + LipoMin two-step EV isolation process. Show less

Tumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial-mesenchymal transition (EMT) and STAS. Our study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin-eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist. In this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence-free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis. STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS. Show less