Biomarkers最新文献

Background: Early-stage breast cancer (BC) shows heterogeneous recurrence risk. Circulating tumor DNA (ctDNA) is promising non-invasive biomarker for minimal residual disease and recurrence prediction, though prognostic performance varies by assay and context.

Methods: Eligible studies on ctDNA-based recurrence and survival were identified through comprehensive searches, quality assessed, and analyzed using random-effects meta-analysis to estimate pooled hazard ratios for clinical outcomes. Heterogeneity (I², τ², Cochran's Q), subgroup (detection method or assay type), and sensitivity analyses were performed to examine the consistency and robustness of results.

Results: For recurrence-free survival endpoints, the pooled HR was 3.28 [95% CI: 1.81; 5.93], indicating a high risk of recurrence-related events among ctDNA-positive patients, though substantial heterogeneity was observed (I² = 93.3%). Pooled effect sized for overall survival (8.92 HR [0.45; 177.87], I² = 74.7%) and recurrence/relapse (5.21 [0.98; 27.69], I² = 84.4%) indicating substantial heterogeneity. Subgroup analysis showed lower heterogeneity with digital PCR and personalized ctDNA assays, and sensitivity testing confirmed result stability (2.47 [1.89; 3.23], I² = 0%).

Conclusion: CtDNA positivity, detected through mutation-based assays strongly associated with increased risk for early recurrence in early-stage BC. Digital PCR and personalized assays demonstrated superior consistency; however, prospective trials are needed to establish its clinical utility.

Background: Accessible biomarkers to predict conversion to Alzheimer's disease and other dementias in Mild Cognitive Impairment (MCI) are urgently needed. Plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are leading candidates, but their utility remains debated.

Objective: We systematically reviewed the prognostic value of plasma NfL and GFAP in MCI using Robust Bayesian Meta-Analysis (RoBMA) to formally model and adjust for publication bias.

Methods: We searched major databases through September 2025 for longitudinal cohort studies (Protocol: OSF 10.17605/OSF.IO/974ZD). RoBMA synthesized hazard ratios while adjusting for small-study effects. Risk of bias (QUIPS) and certainty (GRADE) were assessed.

Results: We included 63 studies. For plasma GFAP (k = 3), Bayesian meta-analysis found moderate evidence for an association with dementia conversion (HR: 1.58, 95% CrI [1.00, 2.24]; Inclusion BF = 9.03). Conversely, for plasma NfL, the prognostic signal was driven by decisive publication bias (Bias BF > 4,000,000). After bias adjustment, the effect of NfL on conversion was null (HR: 1.00; Inclusion BF = 0.011). Evidence certainty was Low to Very Low.

Conclusions: The prognostic value of plasma NfL for dementia conversion appears to be an artifact of publication bias. Plasma GFAP shows a promising but preliminary signal requiring high-quality validation.

Background: Conflicting results on the association of the Val66Met polymorphism in the BDNF gene with anxiety-related disorders are observed from previous studies and meta-analyses. We performed an updated meta-analysis to obtain more precise estimates and add additional analyses not performed by previous reviews.

Methods: Using combinations of various key terms, articles in PubMed, Google Scholar, and Web of Science, written in English were collected until October 31, 2024. Data were extracted independently by two authors and analyzed using Review Manager 5.4.

Results: Fifteen studies that are compliant with the HWE, providing a total of 14,184 participants were included in this meta-analysis after applying predefined inclusion/exclusion criteria based on study design, DSM-based diagnosis, and availability of genotype counts. Most pooled models demonstrated low to moderate heterogeneity with significant associations in the recessive model only. In the subgroup analysis, a significant effect was observed in the PD-uncategorized cohort. The Met/Met genotype demonstrated a suggestive association with increased susceptibility to panic disorder.

Conclusion: Our updated meta-analysis suggests that the Met/Met genotype of the BDNF Val66Met polymorphism may increase susceptibility to PD under a recessive genetic model; however, this evidence remains preliminary.

Introduction: In epithelial ovarian cancer (EOC), surgical outcome is the strongest prognostic factor for survival. However, estimating intra-abdominal tumor burden to plan optimal treatment strategies remains challenging. Moreover, metastases can remain undetected during surgery via visual and tactile inspection. Tumor-targeted molecular imaging has the potential to improve tumor cell identification pre- and intraoperatively. While targeting folate receptor-alpha (FRα) shows promise, other specific biomarkers are needed.

Methods: This study evaluates a novel, data-driven approach using RNA expression data to identify new target proteins for tumor-targeted imaging in EOC. A knowledge platform was utilized to search omics-databases for membrane proteins expressed in EOC but absent or minimally expressed in surrounding tumor-negative and inflammatory cells.

Results: Differential gene expression analysis identified highly expressed genes, which were validated through immunohistochemistry. Two new genes were identified: VTCN1 and AQP5, encoding for proteins B7-H4 and AQP5, respectively. Immunohistochemical validation showed that B7-H4 expression aligned with RNA levels, indicating its potential as a new target. In contrast, there was a discrepancy in AQP5 expression at the protein level compared to its gene counterpart.

Discussion: While this approach was valuable in identifying novel targets for tumor targeted imaging of EOC, immunohistochemistry or cell studies remain imperative for validation of RNA expression results.

Aim: Inflammation and immune dysfunction significantly impact cancer progression and treatment responses. This retrospective study investigated inflammatory parameters and ferritin in predicting immunotherapy response in non-small cell lung cancer (NSCLC) patients.

Methods: The study included 199 patients with NSCLC who received nivolumab between 2018 and 2024 at five medical centers. Various inflammatory markers were also evaluated. Ferritin levels at diagnosis and pretreatment were also evaluated.

Results: ROC curve analyses showed ferritin delta had high prognostic performance for PFS and OS, with AUC values of 0.70 and 0.73. PIV and PNI were significantly associated with PFS and OS. In Kaplan-Meier analyses, PNI was the most consistent prognostic factor. Low PNI (≤43.5) significantly associated with shorter OS (5.0 vs. 15.0 months, p = 0.001) and shorter PFS (4.0 vs. 8.0 months, p = 0.002). High mGPS (score 2) and elevated PIV showed significant prognostic value. In multivariate Cox regression, PNI demonstrated independent prognostic significance. Objective response rate was the strongest prognostic factor for PFS (HR = 0.188, 95%CI: 0.114-0.309, p < 0.001).

Conclusion: These findings highlight the prognostic value of inflammatory and nutritional markers in patients with NSCLC receiving immunotherapy. PNI demonstrated the most consistent prognostic value across multiple analytical approaches and maintained significance in the multivariate analysis.

Objective: Lenvatinib shows efficacy for tumor response and survival in patients with advanced hepatocellular carcinoma (HCC). We aim to assess the effect of lenvatinib on liver function.

Methods: This single-center retrospective cohort study included 40 patients with advanced HCC who received ≥ 2 months of lenvatinib treatment from January 2020 to January 2024 and had at least one efficacy and safety assessment.

Results: The ALBI score showed a slight but significant increase of 0.112 points, from -2.517 at baseline to -2.405 following 2-month of treatment (P < 0.05). With a median follow-up of 18.5 months, the median overall survival was 22.8 months (95% CI: 16.3-29.3), and the median progression-free survival was 12.7 months (95% CI: 9.1-16.3). Both COX regression and Kaplan-Meier analyses indicated that impaired baseline liver function was associated with adverse clinical outcomes. Additionally, treatment response emerged as an independent prognostic factor.

Conclusions: The baseline ALBI score serves as a key prognostic marker, highlighting the necessity for meticulous monitoring of hepatic function, particularly in patients with compromised baseline liver reserve.

Limitations: The limitations of this study include its retrospective design and the potential for selection bias arising from the requirement for at least 2 months of treatment.

Background: Iron overload can promote the generation of reactive oxygen species (ROS), leading to oxidative stress and different human diseases. The trace element selenium has biological functions and can act as both an antioxidant and a prooxidant. This study aimed to evaluate the protective effects of selenium against iron overload-induced toxicity in rats. Adult Wistar rats were exposed to three increasing concentrations of iron (25, 50, and 100 mg/kg body weight [b.w.]), either alone or in combination with selenium (0.5 mg/kg b.w.).

Methods: The biological interactions between these two compounds were investigated at the biochemical level in the liver, spleen, kidney, and pancreas.

Results: Our results indicated that iron used alone induces oxidative stress. In all tissues studied and at all the administered doses, we observed changes in the levels of catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA), and acetylcholinesterase (AChE). The responses were dose- and organ-dependent. Selenium administered at 0.5 mg/kg b.w. attenuate the adverse effects of the different iron dosages.

Conclusion: These findings highlight the potential application of selenium in mitigating oxidative stress and organ toxicity associated with iron overload. Our research carries significant implications for the development of nutritional and therapeutic strategies aimed at managing disorders related to iron metabolism.

Aim: Our study aimed to preliminarily investigate the role of combined detection of serum CCL20 and Oncostatin M in the diagnosis of early-stage endometrial cancer (EC).

Methods: A retrospective study was conducted on 109 patients with early-stage EC. Serum CCL20 and Oncostatin M levels were determined, and their correlations with sex hormone indicators (TTE and DHEAS) in EC patients were analyzed. Influencing factors for EC and the early diagnostic value of each indicator were analyzed.

Results: Serum CCL20 and Oncostatin M were high in EC patients and positively correlated with TTE and DHEAS. Elevated CCL20 and Oncostatin M were independent risk factors for EC. The diagnostic efficacy of serum CCL20 + Oncostatin M in combination was better than that of serum CCL20, Oncostatin M, CA125, and HE4 alone. The diagnostic test combining serum CCL20 and Oncostatin M in endometrioid carcinoma demonstrated an AUC of 0.855, with a sensitivity of 68.00% and a specificity of 92.86%, comparable to that in the whole early-stage endometrial carcinoma group (AUC = 0.867).

Conclusion: Combined detection of serum CCL20 and Oncostatin M may offer a promising adjunctive approach for the diagnosis of early-stage EC, with their levels correlated to sex hormone and clinicopathological characteristics.

Background: This study investigates the pathogenesis of Pigmented Villonodular Synovitis (PVNS) using bioinformatics approaches shared with atherosclerosis (AS).

Methods: Common genes from GSE3698 and GSE28829 were identified. A PPI network was constructed using the STRING database and analyzed with Cytoscape, MCODE, and cytoHubba to determine hub genes. These underwent GO and KEGG enrichment analysis. Candidate genes were identified by integrating cytoHubba and machine learning, and validated via immunohistochemistry and the GSE100927 dataset. Immune infiltration in PVNS and its association with candidate genes were examined, followed by scRNA-seq analysis using GSE155527.

Results: Analysis of 43 shared genes implicated immune responses in both diseases. CSF2RB was identified as a key candidate gene through PPI, machine learning, and immunohistochemistry. Immune infiltration confirmed immune dysregulation and linked CSF2RB to multiple immune cells. scRNA-seq revealed increased macrophages, T cells, and endothelial cells in PVNS, with CSF2RB highly expressed in macrophages and mast cells.

Conclusion: CSF2RB may serve as a diagnostic and therapeutic target for PVNS. scRNA-seq indicates disrupted immune cell composition in PVNS, characterized by significant increases in macrophages and T cells.

Introduction: Volatile gas exposure and self-reported liver conditions share pathophysiologic risk factors, but their exact association remains unclear.

Methods: We used a weighted multivariable-adjusted logistic regression model, using data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Integrative analyses of Non-alcoholic fatty liver disease (NAFLD), liver fibrosis, liver cirrhosis GWAS summaries and blood expression quantitative trait loci (eQTLs) were conducted via summary data-based MR (SMR) and colocalization analysis to prioritize putative blood smoking-related genes and their associations with each liver condition risk. Finally, we further verified these gene-disease causal links through MR and colocalization analysis.

Results: 12,099 NHANES participants were included. Male sex, 46-75 years, and smoke exposure correlated positively with LC; age and smoke exposure remained positively associated with LC incidence after adjustment, while non-Hispanic Black was a LC protective factor. SMR identified three blood-derived candidate genes: RGPD8 (Beta = -0.207), COX6B2 (Beta = -0.567), DNAJC27 (Beta = 0.859). MR and colocalization confirmed their associations with cirrhosis, fibrosis, and NAFLD, respectively.

Conclusion: This study confirms a causal link between smoke exposure and increased LC risk, identifies novel gene-disease associations, and provides cross-disciplinary insights for targeted LC prevention and personalized research.