International Journal of Biological Markers最新文献

Background: Several studies have suggested an association between tumor-associated autoantibodies (TAAbs) and breast cancer. However, most research has focused on imaging techniques, with few studies examining the combined use of TAAbs and imaging to distinguish benign and malignant breast nodules.

Methods: Our study included 197 women with breast nodules. We collected clinical data, preoperative breast ultrasonography, and mammography results. Serum TAAbs were detected using enzyme-linked immunosorbent assay. Logistic regression analysis assessed the ability of factors to distinguish benign from malignant nodules. Receiver operating characteristic curves were plotted, and predictive models were constructed.

Results: Five TAAbs (BRCA2, TP53, ATAD2, NY-ESO-1, CAGE) exhibited significant differences (p < 0.001) between benign and malignant breast nodules, with specificity of 95.83% (area under the curve  = 0.722). Pearson's χ² results revealed a close association between the levels of 5-TAAbs and breast cancer stages. Additionally, preoperative 5-TAAbs combined with ultrasonography and mammography increased diagnostic accuracy of benign nodules by 10.42% and reduced misdiagnosis of malignant nodules by 14.85%. Multivariate logistic analysis identified age (p < 0.001), preoperative 5-TAAbs (p = 0.004), breast ultrasonography (p = 0.01), and mammography (p < 0.001) as independent factors for malignant nodules. Combining 5-TAAbs with age and imaging improved differentiation, achieving sensitivity of 85.42% and specificity of 94.06%.

Conclusion: Tumor-associated autoantibodies, especially the 5-TAAbs, have certain clinical value in the early diagnosis of breast cancer and can serve as an effective auxiliary tool for preoperative breast ultrasonography and mammography in patients with breast nodules.

PurposeThis study aimed to investigate the role of SH3GL1 in regulating B7-H3 expression and its impact on immune escape in non-small cell lung cancer (NSCLC).MethodsSH3GL1 and B7-H3 expression levels were analyzed in The Cancer Genome Atlas datasets and NSCLC cell lines using quantitative reverse transcription polymerase chain reaction and Western blot. SH3GL1 overexpression was performed to assess its effect on B7-H3 expression. Co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were used to confirm the interaction and co-localization of SH3GL1 and B7-H3. Flow cytometry and confocal microscopy were employed to study B7-H3 endocytosis and recycling. The functional impact of SH3GL1 on immune escape was evaluated through T cell co-culture assays and in vivo tumor models.ResultsSH3GL1 and B7-H3 were significantly upregulated in NSCLC clinical samples and cell lines. SH3GL1 overexpression increased B7-H3 protein levels and promoted its recycling to the cell surface by redirecting B7-H3 away from lysosomal degradation. Co-IP and IF confirmed the physical interaction and co-localization of SH3GL1 and B7-H3. In vitro, SH3GL1 overexpression suppressed T cell proliferation, cytotoxicity, and activation while increasing immunosuppressive cytokines. In vivo, SH3GL1 overexpression accelerated tumor growth, increased Treg infiltration, and enhanced B7-H3 expression in tumor tissues.ConclusionSH3GL1 impacts B7-H3 expression and promotes immune escape in NSCLC by enhancing B7-H3 recycling and suppressing T cell function. These findings highlight SH3GL1 as a potential therapeutic target to overcome immune escape in NSCLC.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. The aim of this study was to comprehensively analyze the clinical, cytomorphological, and flow cytometry characteristics of DLBCL patients, with a focus on bone marrow involvement (BMI), to identify novel prognostic factors.MethodsThe clinical, cytomorphological, and flow cytometry characteristics of 220 DLBCL patients were collected from January 2017 to April 2024. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors for overall survival (OS). Kaplan-Meier survival curves were generated. Logistic regression analyses were used to explore associations between clinical, cytomorphologic, and immunophenotyping features.ResultsThe median age of the patients was 63 years, with 48.6% showing positive BMI. Multivariate analysis confirmed that age, lactate dehydrogenase (LDH) level, hemoglobin (HGB) level, and platelet count (PLT) were independent prognostic factors for OS. Compared with patients without BMI, patients with BMI presented significant differences in laboratory parameters, such as lower lymphocyte counts and elevated inflammatory marker levels. Cytomorphological analysis of bone marrow smears revealed associations between specific cell characteristics (e.g., large cell size, medium cytoplasmic volume, and pseudopod protrusions) and immunophenotypic markers (e.g., CD23, CD79b, and cKappa).ConclusionAge, LDH, HGB, and PLT were identified as independent prognostic factors for OS. The integration of cytomorphological and flow cytometry data may provide additional insights into disease biology. Furthermore, this study highlighted that DLBCL patients with BMI have lower lymphocyte, PLT, and elevated levels of markers such as LDH, high-sensitivity C-reactive protein and β2-microglobulin.

BackgroundCircular (circ)RNAs are essential regulators in cancer development and progression. CircPVT1, derived from exon 2 (410 nucleotides) of PVT1 gene located at 8q24, has been widely recognized as an oncogenic circRNA frequently upregulated in various human cancers. This study aimed to assess the diagnostic accuracy of circPVT1 for human cancers.MethodsArticles published up to July 2024 were searched across four databases (PubMed, EMBASE, Web of Science, and Cochrane databases). A meta-analysis was conducted under a random effects model and the diagnostic performance was evaluated using receiver operator characteristic curve analysis. Subgroup analysis of circPVT1 in different cancer types and tissues was performed.ResultsOverall, 12 studies (1246 patients) were included for diagnostic outcome synthesis. The pooled sensitivity was 0.83 (95% CI, 0.77-0.88) and specificity of 0.80 (95% CI, 0.73-0.87), with an area under the receiver operator characteristic curve of 0.89 (95% CI, 0.86-0.91), highlighting the robust diagnostic value of circPVT1. Multiple studies have revealed that circPVT1 functions as a micro RNA sequester to modulate downstream gene expression, affecting various malignant behaviors in cancers.ConclusionThis study enhances our understanding of the role and mechanism of circPVT1 in human cancers and supports its potential as a promising diagnostic biomarker for various cancer types.

BackgroundThe mechanisms underlying the occurrence and progression of metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis remains poorly understood. This study aims to identify key transcription factors involved in the development of liver fibrosis in MASH patients, thereby providing potential targets for drug discovery.MethodsMicroarray data were retrieved from liver biopsy specimens of MASH patients exhibiting varying stages of fibrosis via the Gene Expression Omnibus database. Differentially expressed transcription factors (DETFs) were identified through the application of Weighted Gene Co-expression Network Analysis. A set of in vitro and in vivo experiments were conducted to investigate the role of MEOX1 in MASH-related fibrosis. To delineate the potential mechanisms, the transcriptomic RNA sequencing (RNA-seq), Alphafold, and PyMOL were used.ResultsA total of six DETFs (MEOX1, SOX4, LEF1, SOX9, MYC, and CBX2) were identified as being positively correlated with the progression of MASH-related fibrosis. MEOX1 was increased in mouse model of MASH diet-induced liver fibrosis and hepatic stellate cells (HSCs) stimulated by transforming growth factor-β1. Knockdown of the MEOX1 markedly suppressed the activation, proliferation, and migration of HSCs. RNA-Seq analysis identified serine protease inhibitor family E member 1 (SERPINE1) as the critical target of MEOX1 within HSCs. The protein interaction sites of MEOX1 and SERPINE1 were predicted using Alphafold and PyMOL.ConclusionIn summary, as a pivotal transcription factor, MEOX1 activates HSCs via SERPINE1, thereby promoting liver fibrosis associated with MASH. Inhibition of the MEOX1-SERPINE1 pathway could offer a novel therapeutic avenue for treating MASH-related fibrosis.

IntroductionDiagnosis and monitoring of metastatic colorectal cancer (mCRC) depend on diagnostic imaging. Circulating carcinoembryonic antigen (CEA) can be analyzed but no optimal, non-invasive biomarker exists. Circulating collagen IV (COL IV) is a promising biomarker in patients with colorectal liver metastases (CLM). This study aimed to evaluate COL IV and other cancer-related and stroma-derived proteins as biomarkers for mCRC.Materials & methodsPlasma COL IV and 10 other proteins were analyzed with ELISA and Luminex multiplex assays.ResultsmCRC patients have elevated levels of circulating COL IV, CEA, interleukin-8 (IL-8), hepatocyte growth factor (HGF), cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and migration inhibitory factor (MIF) compared to primary CRC (pCRC) patients. COL IV is elevated in mCRC patients compared to healthy individuals. Levels of COL IV, CEA, OPN, CYFRA 21-1, IL-8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were dependent on the metastatic site. OPN, CEA, and HGF are very good at discriminating between mCRC patients and pCRC controls. COL IV is very good at distinguishing between mCRC patients and healthy controls. The combination of OPN + CEA is superior at detecting mCRC than CEA alone. High HGF and COL IV levels correlate to poor prognosis.ConclusionOPN, CEA, and HGF are potential biomarkers for mCRC. COL IV is a potential biomarker for CLM. The combination of OPN with CEA is superior to CEA alone in detecting mCRC. Levels of circulating proteins depend on metastatic localization, implying that a combination of markers is better than single markers in detecting mCRC disease. High levels of COL IV and HGF have potential prognostic value.

BackgroundKin17 is critical in regulating the proliferation and metastasis of tumors in various malignancies. However, the relationship between Kin17 expression, clinicopathologic features, and esophageal squamous cell carcinoma (ESCC) prognosis remains unclear.MethodsThe analysis of Kin17 messenger RNA (mRNA) expression involved the utilization of data from The Cancer Genome Atlas (TCGA) dataset through the platforms the University of ALabama at Birmingham CANcer data analysis portal (UALCAN) and the Gene Expression Omnibus (GEO). To determine the expression levels of Kin17 in tissues, immunohistochemistry was conducted. Using Pearson's chi-square test, the relationship between Kin17 expression and clinicopathological variables was evaluated. Cox proportional hazard models (both univariate and multivariate), receiver operating characteristic (ROC) curves, and Kaplan-Meier survival curves were used to analyze survival.ResultsIn both the TCGA and GEO datasets, the mRNA level of Kin17 was greater in tumor tissues when compared to tumor-adjacent tissues (P < 0.001). Similarly, there was a significant expression of Kin17 (P < 0.0001) in ESCC tissues. Elevated Kin17 expression correlated significantly with increased Ki-67 levels (P < 0.001), advanced pathological tumor node metastasis stage (P = 0.01), and positive lymph node metastasis (P = 0.02). According to univariate and multivariate Cox models, high Kin17 expression was associated with poorer progression-free survival (PFS) (hazard ratio (HR): 1.990, 95% confidence interval (CI): (1.040-3.810)), and Kin17 was an independent prognostic variable for overall survival (OS) (HR: 2.321, 95% CI: (1.056-5.101)). ROC curve showed that the area under the curve for predicting PFS and OS using the combination of Kin17 and K-i67 was 0.7088 and 0.7031, respectively. High Kin17 expression was associated with unfavorable PFS (HR: 2.009, 95% CI: (1.059-3.811)) and OS (HR: 2.997, 95% CI: (1.488-6.040)).ConclusionsKin17 is abundantly expressed in ESCC tissues and is potentially useful for prognostic evaluation and as a target for therapeutic interventions in ESCC.

BackgroundNasopharyngeal carcinoma has unique epidemiological characteristics. Screening for this currently lacks a highly efficient, non-invasive, and inexpensive method. Serum microRNA (miRNA), which is stable and commonly present, has the potential to serve as a novel marker for nasopharyngeal carcinoma diagnosis.ObjectivesThis study aims to find a highly efficient, non-invasive, and inexpensive biomarker for nasopharyngeal carcinoma diagnosis.MethodsThis study, involving 52 patients with nasopharyngeal carcinoma and 56 healthy controls, was conducted in two phases to identify miRNAs in the serum suitable for nasopharyngeal carcinoma diagnosis using quantitative reverse transcription polymerase chain reaction. Stepwise logistic regression analysis was then used to identify a miRNA panel with high diagnostic efficiency. Additionally, we used bioinformatic analysis to explore the potential biological functions of the crucial miRNAs.ResultsA three-miRNA panel (miR-148b-3p, miR-10b-5p, and miR-18a-5p) has a high diagnostic value for nasopharyngeal carcinoma (area under the curve = 0.872; 95% confidence interval: 0.793-0.928; sensitivity = 78.57%; specificity = 86.54%). Through bioinformatics analysis we found that CC2D2B, PCDH9, and FOXP1 may be potential target genes of these three miRNAs.ConclusionThis three-miRNA panel (miR-148b-3p, miR-10b-5p, and miR-18a-5p) represents a highly efficient, non-invasive, and inexpensive biomarker for diagnosing nasopharyngeal carcinoma.

BackgroundNicotinamide N-methyltransferase (NNMT), a metabolic enzyme in the liver, has been implicated in various biological processes, and its high expression in hepatocellular carcinoma has been linked to tumor metastasis and poor prognosis. However, its potential as a serum biomarker for hepatocellular carcinoma diagnosis remains unexplored.MethodsA total of 172 subjects were included in this study, consisting of 71 hepatocellular carcinoma patients (64 with hepatitis B virus (HBV)-associated hepatocellular carcinoma and 7 with non-HBV-associated hepatocellular carcinoma), as well as 70 healthy controls and 31 HBV-infected individuals. Serum NNMT levels were measured, and clinical-pathological correlations were analyzed. The diagnostic efficacy of serum NNMT for HBV-related hepatocellular carcinoma was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsSerum NNMT levels were significantly elevated in HBV-infected individuals and correlated with poorer prognosis, including reduced overall survival and shorter disease-free survival. Kaplan-Meier analysis revealed that low NNMT expression was associated with longer overall survival (75 vs. 12 months, P < 0.0001) and disease-free survival (21.5 vs. 5 months, P < 0.01). In HBV-related hepatocellular carcinoma patients, NNMT levels correlated with biochemical markers including alfa-fetoprotein, aspartate transaminase, triglycerides, total cholesterol, low-density lipoprotein, apolipoprotein B, TB, and albumin, with decreased albumin, and high-density lipoprotein levels promoting NNMT expression. ROC analysis showed that NNMT outperformed alfa-fetoprotein (area under the curve (AUC) 0.869 vs. 0.775), with a sensitivity of 95.2%, specificity of 87.9%, and a combined AUC of 0.947, demonstrating its superior diagnostic value for HBV-related hepatocellular carcinoma.ConclusionsSerum NNMT is a promising biomarker for predicting the risk of hepatocellular carcinoma in HBV-infected individuals and may serve as an indicator for the prognosis of hepatocellular carcinoma patients.