International Journal of Biological Markers最新文献

PurposeAlthough human lysine oxidase-like 3 (LOXL3) is associated with various cancers, its role in pleural mesothelioma (PM) remains uncharacterized. This study investigated the expression level and prognostic association of LOXL3 in PM.MethodsTissue specimens were collected from patients with PM. The expression levels of LOXL3 were assessed using immunohistochemistry, Western blot analysis, and quantitative reverse transcription PCR. The clinical correlation analysis was conducted using R software (version 3.6.3), incorporating data from both The Cancer Genome Atlas and Chuxiong cohorts. Univariate and multivariate Cox proportional hazards regression models alongside Kaplan-Meier survival curve analysis were performed to evaluate prognostic significance. Additionally, gene expression correlation studies between LOXL3 and other members of the LOX family were performed using the Gene Expression Profiling Interactive Analysis platform. Finally, Gene Set Enrichment Analysis was conducted to identify the signaling pathways associated with LOXL3.ResultsLOXL3 exhibited significant upregulation in both sarcomatoid and biphasic PM subtypes compared to the control samples. Clinico-pathological analysis revealed the correlations between LOXL3 expression levels and cancer type, and Wilms tumor protein 1 (WT-1) status. Cox regression analysis identified cancer type as an independent prognostic factor. Kaplan-Meier analysis demonstrated obviously poorer survival rates in cohorts with high LOXL3 expression. Notably, coordinated expression patterns were observed between LOXL3 and LOXL4. The protein expression level of LOXL3 exhibits a positive correlation with CD68, CD206, and programmed death-ligand 1 (PD-L1), with this correlation being particularly pronounced in sarcomatoid mesothelioma. Functional enrichment analysis indicated that high LOXL3 expression was primarily associated with pathways related to oxidative phosphorylation, late and early estrogen response, and adipogenesis.ConclusionLOXL3 is highly expressed in PM and associated with poor prognosis, and is involved in tumor immune evasion. The expression level of LOXL3 is correlated with cancer types and the expression level of WT-1. Cancer type is an independent prognostic factor for PM. LOXL3 expression is positively associated with LOXL4, and high LOXL3 expression is enriched in oxidative phosphorylation, estrogen response, and adipogenesis pathways, while the low-expression group is enriched in apoptosis, interleukin-2/signal transducer and activator of transcription 5, mammalian target of rapamycin complex 1, and transforming growth factor-β pathways. CD68, CD206, PD-L1, and LOXL3 may collaboratively contribute to the regulation of the PM microenvironment and are closely linked to the invasion and metastasis of PM. Therefore, LOXL3 can be used as both a prognostic marker and a potential therapeutic target for PM.

IntroductionMatrix metalloproteinases (MMPs) are enzymes participating in tumorigenesis and tumor progression through their proteolytic and cell-signaling properties. They are regulated mostly by endogenous tissue inhibitors of metalloproteinases (TIMPs). The expression of both MMPs and TIMPs is often altered in cancers. Many studies investigated their potential as circulating cancer biomarkers, with confounding results, which might be induced by preanalytical issues, particularly by using serum instead of plasma. The study aims to investigate plasma levels of selected MMPs and TIMPs in association with the diagnosis and prognosis of colorectal cancer.MethodsThe clinico-pathological data of 148 patients operated for colorectal cancer were collected from the medical records system at the University Hospital Pilsen. Sixty-eight age-matched healthy subjects were included as controls. Plasma levels of MMP-2, -7, -8, -9, -10, and TIMP-1, -2, -3, and -4 were assessed with multiplex immunoassays with the technology xMAP.ResultsMMP-8 and -9 levels were significantly elevated in patients (P= 0.0002 and 0.0009, respectively), TIMP-2 levels were significantly decreased in colorectal cancer patients (P = 0.0016). When comparing the early colorectal cancer (stage I and II) with advanced colorectal cancer (stage III and IV), MMP-8 and TIMP-1 were significantly increased in advanced colorectal cancer (P = 0.0173 and <0.0001, respectively). The area under the curve and the receiver operating characteristic were between 0.680 and 0.530 for all studied biomarkers. In univariate analysis, overall survival was significantly elevated in patients with MMP-7, -8, or TIMP-1, which was higher than cut-offs (hazard ratio = 4.57, 2.03, and 7.64, respectively).ConclusionThese findings suggest that plasma MMP-7, MMP-8, and TIMP-1 are potential prognostic biomarkers for colorectal cancer . None of the investigated biomarkers revealed diagnostic potential.

PurposeThis study aimed to identify genes associated with sensitivity to anti-programmed death-ligand 1 (PD-L1) immunotherapy in lung squamous cell carcinoma (LUSC) using bioinformatics approaches and to validate their functional relevance through in vitro experiments.MethodsTranscriptomic datasets from The Cancer Genome Atlas were analyzed to screen candidate genes, and UBE2C was identified as a key target. Functional enrichment analysis (Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to explore its potential biological roles. To investigate its regulatory effects, UBE2C was overexpressed or silenced in LUSC cells, with or without PD-L1 inhibitor treatment. Real time-quantitative polymerase chain reaction and Western blot were used to assess changes in gene/protein expression and pathway activation. Enzyme-linked immunosorbent assay and lactate dehydrogenase assays were employed to evaluate cytokine secretion (interferon (IFN)-γ, interleukin (IL)-2) and cytotoxicity. Additionally, immunofluorescence was used to examine UBE2C and PD-L1 co-expression in patient tissues stratified by PD-L1 expression levels.ResultsUBE2C expression was significantly higher in PD-L1 high-expression tissues than in low-expression tissues at both messenger RNA and protein levels. Compared with control groups, UBE2C overexpression activated the AKT/PI3 K pathway and increased IFN-γ and IL-2 secretion, whereas knockdown produced the opposite effect. Combined treatment with UBE2C overexpression and a PD-L1 inhibitor further enhanced cytokine release and cytotoxicity relative to PD-L1 inhibitor alone. Immunofluorescence analysis confirmed the co-localization of UBE2C and PD-L1 in tissues with high PD-L1 expression.ConclusionUBE2C was identified as a gene associated with increased sensitivity to anti-PD-L1 immunotherapy in LUSC. Functional experiments suggest that UBE2C may enhance anti-tumor immune responses and improve immunotherapy efficacy, providing a potential biomarker and therapeutic target for personalized treatment.

ObjectiveCervical cancer (CC) is among the most prevalent malignancies globally. Public sequencing data indicate that PAX8-AS1 is associated with gynecological cancers, including CC, but its specific function and mechanism in cervical cancer remain unclear. The present study aimed to elucidate the role of PAX8-AS1 and its target axis in the CC.MethodsA total of 104 CC patients were included. The levels of PAX8-AS1, miR-675-3p, and decorin (DCN) were quantified by quantitative reverse transcription polymerase chain reaction. Survival curve and Cox regression predicted prognostic factors. Proliferation and invasion/migration were assayed by CCK-8 and Transwell in CC cell lines. The target relationship was verified by dual-luciferase reporter assay and co-transfection.ResultsPAX8-AS1 was declined in CC tumor tissue and cell lines. PAX8-AS1 was an independent prognostic factor. PAX8-AS1 expression was associated with the CC pathological including the international federation of gynecology and obstetrics staging system (FIGO), tumor size, and lymph node metastasis. Patients with higher PAX8-AS1 levels had better survival outcomes. Upregulation of PAX8-AS1 inhibited the CC cell invasion, migration, and proliferation. miR-675-3p was predicted and verified as sponged of PAX8-AS1. miR-675-3p was negatively related to PAX8-AS1. PAX8-AS1 impeded the CC cellular function by regulating miR-675-5p. DCN was confirmed as the target of miR-675-5p. DCN was negatively and positively related to miR-675-3p and PAX8-AS1, respectively. PAX8-AS1 suppressed the CC cell invasion, migration, and proliferation by targeting miR-675-3p/DCN axis.ConclusionIn summary, PAX8-AS1 was related to tumor progression and inhibited CC development. As a potential biomarker, PAX8-AS1 impeded CC cell invasion, migration, and proliferation by regulating the axis of miR-675-3p/DCN.

ObjectiveThe objective of this study is to investigate the correlation between the expression levels of midkine (MDK) in the serum of patients with hepatocellular carcinoma (HCC) and various clinical features, and to evaluate the diagnostic efficacy of MDK in HCC cases that are negative for alpha-fetoprotein (AFP).MethodsSerum samples from 330 patients were collected from electronic cases and divided into three groups: HCC, benign liver disease, and healthy people. Serum MDK levels in all three groups were detected by ELISA. Correlation analysis was conducted to evaluate the relationship between serum MDK and liver function indexes and other traditional tumor markers in the HCC group. The receiver operating characteristic curve was used to analyze the diagnostic utility of MDK in HCC and AFP-negative HCC. In addition, univariate and multivariate analyses were performed to determine the correlation between MDK level and tumor metastasis, and clinicopathological features.ResultsMDK is significantly elevated in negative HCC (P = 0.001). The serum expression level of MDK in patients with HCC was found to be positively correlated with various indicators of liver injury (P < 0.05). Notably, elevated MDK expression was significantly associated with the China liver cancer staging system (CNLC) stage (P = 0.003) and complications (P = 0.000). Furthermore, the CNLC stage significantly impacted patient survival and metastasis (P = 0.016). Specifically, we propose that high levels of MDK expression are closely linked to poor tumor prognosis.ConclusionThe risk of tumor metastasis and the likelihood of poor prognosis in patients with HCC are significantly elevated in those exhibiting high levels of MDK. MDK could serve as a novel serum diagnostic marker for patients who are negative for AFP.

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.