Biomarkers最新文献

Background: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide, with a median overall survival of approximately 12 months. The proto-oncogene c-MYC is among the most frequently activated oncogenes, implicated in roughly 20% of all malignancies.

Methods: PubMed, Embase, and Web of Science were systematically searched for studies evaluating the association between c-MYC expression and (1) disease-specific survival (DSS) and (2) overall survival (OS). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a fixed-effects model. A two-sided p ≤ 0.05 was considered statistically significant.

Results: Across 15 studies encompassing 2,372 gastric cancer patients (802 c-MYC-positive; 410 male), male gender was strongly associated with c-MYC positivity (OR 8.83; 95% CI 5.74-13.56; p < 0.00001), as were deeper invasion (T3-T4 vs T1-T2: OR 0.38; 95% CI 0.24-0.60; p < 0.00001) and advanced stage (III-IV vs I-II: OR 2.69; 95% CI 1.71-4.23; p < 0.00001). Patients with c-MYC-negative tumors exhibited a markedly higher DSS compared to those with c-MYC-positive tumors (HR 3.73; 95% CI, 2.22-6.26; p < 0.0001).

Conclusion: Our findings identify c-MYC as a significant prognostic biomarker for disease-specific survival in gastric cancer.

Introduction: Endometriosis is an estrogen-dependent condition characterized by ectopic implantation of endometrial tissue; molecular mechanisms underlying lesion persistence remain incompletely understood. Aquaporins (AQPs), transmembrane water channels involved in migration and proliferation, have been implicated in endometriosis pathophysiology, although data on AQP9 are limited.

Methods: This prospective case-control study evaluated AQP9 concentrations in serum, peritoneal fluid, and cervicovaginal secretions of women with endometriomas compared with healthy surgical controls. Twenty-seven women with unilateral endometrioma and 30 undergoing bilateral tubal ligation were included. AQP9 levels were measured using ELISA, and analyses included correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression adjusted for age, body mass index (BMI), gravida and parity.

Results: Peritoneal fluid AQP9 concentrations were significantly higher in women with endometriomas than in controls (275 [58-669] vs. 171.5 [6.6-507] ng/mL, p = 0.023), whereas serum and cervicovaginal AQP9 levels showed no differences. ROC analysis demonstrated high sensitivity (92.6%) but limited specificity (43.3%). Logistic regression confirmed that peritoneal AQP9 > 128 ng/mL was independently associated with endometrioma (OR 4.40, 95%CI 1.66-29.28, p = 0.025). Serum AQP9 was inversely correlated with endometrioma size (p = 0.008).

Conclusion: Peritoneal AQP9 elevation reflects alterations in the local peritoneal microenvironment, supporting its potential role in the pathophysiology of endometriosis.

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. 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. 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. 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.

AimInflammation 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.MethodsThe 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.ResultsROC 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).ConclusionThese 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.

This study evaluates dielectric conductivity as a diagnostic tool for assessing lead (Pb) levels in albino rats. It also investigated the ameliorative potentials of nano-ZnO-capped sodium carboxymethyl cellulose (nZnO/CMC), synthesized using co-precipitation technique. The average crystallite size obtained from X-ray diffraction measurements is 33 nm. The effect of Pb induced toxicity were evaluated using four groups of six albino rats each, administered with Pb for 61 days. Haematological results show decreasing trends in packed cell volume, red blood and white blood cell counts, and haemoglobin concentration with Pb administration, indicating anaemia. Upon nZnO/CMC administration, both haematological and erythrocyte surface sialic acids parameters were restored, suggesting that nZnO/CMC has Pb chelating capabilities. Toxicity studies revealed nZnO/CMC to be non-toxic to tissues below 2000 mg/kg body weight per os. Dielectric conductivity of normal and exposed blood samples measured between 200 Hz and 4 MHz shows dominance of ionic conductivity; highest for Pb-exposed samples and lowest for the normal/control sample. It also showed a decreasing trend for samples treated with nZnO/CMC at 100 and 200 mg/kg. This work strongly correlates changes in dielectric ionic conductivity with haematological/Pb exposure concentration, suggesting that dielectric ionic conductivity of blood is a promising biomarker for Pb-exposed animals.

Background: The leukocyte-specific protein 1 (LSP1) has been implicated in cancer progression, and this paper aims to reveal the prognostic value and pathogenic role of LSP1 in acute myeloid leukemia (AML).

Methods: The TCGA and GTEx datasets were performed to assess the expression and prognostic significance of LSP1 in AML. qRT-PCR was utilized to detect LSP1 expression in AML patients. The impact of LSP1 knockdown on AML was assessed using CCK-8, 7-AAD/Annexin-V assays, and xenograft mouse models. Gene Set Enrichment Analysis (GSEA), qRT-PCR, and functional experiments were employed to explore and verify the potential signaling pathway of LSP1 in AML.

Results: Our findings revealed that a high expression level of LSP1 indicated poor prognosis for AML. Meanwhile, the knockdown of LSP1 could inhibit AML in vitro and in vivo. Next, we observed that the NF-κB signaling pathway, associated with anti-apoptotic effects, was significantly upregulated in the high LSP1 expression group, and knocking down LSP1 could inhibit it. In addition, we also found that the NF-κB pathway-related anti-AML effect of bortezomib partially relied on LSP1.

Conclusions: This study revealed that LSP1 plays a crucial role in the progression of AML, indicating its potential as a prognostic biomarker and therapeutic target.

Background: Among 6.7 million Americans with heart failure (HF), 40%-60% are estimated to have mild cognitive impairment (MCI) and are at-risk for vascular contributions to cognitive impairment and dementia (VCID). This pilot study examined whether neurodegenerative and inflammatory serum biomarkers are elevated in HF and whether a combination of these biomarkers predicts cognitive performance.

Methods: Thirty-four HF patients (mean age = 69 years, 62% male) were recruited from Banner-University cardiology clinics and underwent blood sampling and neuropsychological testing to derive an 'Actual Composite Cognitive Score.' Age-matched healthy controls included (i) 11 individuals (mean age = 63 years, 20% male) who completed identical procedures and (ii) 24 individuals used exclusively for biomarker analysis. Biomarkers-serum neurofilament light chain (NfL), plasma phosphorylated tau (pTau181, pTau217), placental growth factor (PlGF), cytokines, and NT-proBNP-were quantified using Quanterix Simoa, Milliplex, and Elecsys (Roche) assays.

Result: HF participants scored worse in cognitive assessments than controls (p = 0.0001). Serum NfL (p = 0.02), IL-6 (p < 0.0001), IL-12p40 (p < 0.0001), IL-15 (p = 0.005), MIP-1α (p = 0.007), TNFβ (p = 0.03), and TNFα (p = 0.0002) were increased in HF. NfL and pTau181 correlated with NT-proBNP; NfL, IL-6, and TNFα inversely correlated with cognitive scores. The Composite Biomarker Cognitive Score = NfL + NT-proBNP + IL-6 + TNFα negatively correlated with the Actual Composite Cognitive Score (r = -0.60, p = 0.0002).

Conclusion: These results establish a Composite Biomarker Cognitive Score, which is predictive of cognitive impairment in HF, and may aid in identifying HF patients suitable for cognitive-protective therapies.

Background: Biomarkers for CTD-ILD diagnosis, treatment response evaluation, and pathogenesis elucidation are lacking. Licorice-dried ginger soup alleviates lung injury, but its mechanism is unknown. This study aimed to identify biomarkers of this herbal treatment for CTD-ILD.

Methods: Public datasets of Peripheral blood mononuclear cells (PBMCs) from CTD-ILD (n = 4) and connective tissue disease-associated non-Inflammatory lung disease (CTD-NILD) (n = 3) patients were analyzed using differential expression (p.adj < 0.05 & |log2 Fold Change (FC)| > 0.5), protein-protein interaction networks, and cytohubba algorithms (Top5 genes from six algorithms). Functional enrichment, upstream pathway activity, phosphorylation, molecular regulatory networks, and molecular docking were performed and the expression of biomarkers was validated in clinical samples.

Results: Five biomarkers (CXCL8, IL1A, IL1B, NFE2L2, and PTGS2) were identified. Functional analysis linked these pathways to innate immunity, cytokine activity, and pertussis pathways. Regulatory networks have been implicated in toll-like receptors, chemokine signaling, and DNA replication. Biomarkers correlated with lung injury and showed high expression in the blood/immune cells. Molecular docking confirmed strong binding between the biomarkers and quercetin.

Conclusion: CXCL8, IL1A, IL1B, NFE2L2, and PTGS2 are critical CTD-ILD biomarkers. Licorice ginger soup may target these genes via quercetin, providing novel diagnostic and therapeutic insights.

Objective: Base excision repair (BER) plays a vital role in repairing DNA damage; however, polymorphisms in BER genes may influence an individual's susceptibility to disease risk. We investigated the role of BER genes as a biomarker of susceptibility among agricultural workers in Haryana, India.

Methods: The pesticide-exposed workers (110) and unexposed controls (114) were genotyped for XRCC1 C26304T (rs1799782), XRCC1 G28152A (rs25487), APE1 T2197G (rs1130409), and OGG1 C1245G (rs1052133) using the PCR-RFLP technique. The allelic frequencies were compared using chi-square tests, with a significance level set at p < 0.05.

Results: Significant results were observed for XRCC1: rs1799782 (T allele: 0.1409 vs. 0.0658; OR: 2.32; CI: 1.08-4.99; p: 0.028) and rs25487 (A allele: 0.332 vs. 0.202; OR: 1.90; CI: 1.29-2.80; p: 0.001) between exposed and control groups. The frequency of the APE1 Glu allele was significantly lower in exposed individuals (OR: 0.49; CI: 0.31-0.78; p = 0.003). In contrast, the OGG1 Cys allele was more frequent in the exposed group; however, the difference was not statistically significant (OR: 1.43; CI: 0.91-2.23; p = 0.113).

Conclusion: Our findings suggest that DNA repair gene polymorphism may influence an individual's susceptibility to pesticide exposure, leading to oxidative damage and genotoxic effects.

Background: Several studies have identified that HOTAIR polymorphisms were expressed abnormally in a range of cancers, including breast, gastric, liver, and lung cancers. However, the impact of this gene on colorectal cancer (CRC) remains a topic of debate. To obtain the most accurate results, the association of HOTAIR polymorphisms with CRC risk was analyzed in this meta-analysis (MA).

Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched to find the correlation of HOTAIR polymorphisms with CRC up to February 2024. The association of HOTAIR polymorphisms with CRC susceptibility was assessed using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Five relevant studies were identified in total. In all HOTAIR polymorphism studies involving CRC, it was found that the subgroup analysis by ethnicity revealed that the rs1899663 G > T codominant and dominant models were positively correlated with CRC development in Asian populations and negatively correlated with CRC development in non-Asian populations (Codominant: OR = 0.70, 95% CI = 0.39-1.25; D: Dominant: OR = 0.65, 95% CI = 0.28-1.53).

Conclusions: This MA indicates that HOTAIR polymorphism-the rs1899663 G > T genotype-might have a racially specific impact on CRC risk.