Biomarker Insights最新文献

{"title":"Genetic Association Between Polycystic Ovary Syndrome and the <i>APOA5</i> rs662799 and <i>PLIN1</i> rs894160 Metabolic Variants in the Western Saudi Population: A Case-Control Study.","authors":"Sherin Bakhashab, Asma A Batarfi, Mahinar M Alhartani, Rola Turki, Wessam Mady","doi":"10.1177/11772719241258585","DOIUrl":"10.1177/11772719241258585","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors.</p><p><strong>Objectives: </strong>This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (<i>APOA5</i>; rs662799) and perilipin 1 (<i>PLIN1</i>; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics.</p><p><strong>Design and methods: </strong>This was a case-control study conducted on women with (<i>n</i> = 104) and without (<i>n</i> = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays.</p><p><strong>Results: </strong>Significant and direct associations were detected between PCOS susceptibility and <i>APOA5</i> SNP rs662799 and <i>PLIN1</i> SNP rs894160 (<i>P</i> < .001). For <i>APOA5</i> SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, <i>P</i> < .001) and hypertriglyceridaemia (OR = 17.0, <i>P</i> = .5) than women with the G allele. For <i>PLIN1</i> SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, <i>P</i> < .001). For <i>PLIN1</i> SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, <i>P</i> = .02) and an irregular period (OR = 0.07, <i>P</i> = .040) than women with the AT genotype.</p><p><strong>Conclusion: </strong>We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Serum Proteomes Expressed from Benzene Exposure Among Gasoline Station Attendants.","authors":"Chan Pattama Polyong, Sittiruk Roytrakul, Jintana Sirivarasai, Tanongsak Yingratanasuk, Anamai Thetkathuek","doi":"10.1177/11772719241259604","DOIUrl":"10.1177/11772719241259604","url":null,"abstract":"<p><strong>Background: </strong>Research on the proteomes impact of benzene exposure in fuel station employees remains sparse, underscoring the need for detailed health impact assessments focusing on biomarker evaluation.</p><p><strong>Objectives: </strong>This investigation aimed to analyze the differences in blood parameters and serum proteomes resulting from benzene exposure between gasoline station attendants (B-GSA) and a control group.</p><p><strong>Design and methods: </strong>A cross-sectional analytical study was conducted with 96 participants, comprising 54 in the B-GSA group and 42 in the control group. The methodology employed included an interview questionnaire alongside urine and blood sample collections. The urine samples were analyzed for <i>trans,trans</i>-muconic acid (<i>t,t</i>-MA) levels, while the blood samples underwent complete blood count analysis and proteome profiling.</p><p><strong>Results: </strong>Post-shift analysis indicated that the B-GSA group exhibited significantly higher levels of <i>t,t</i>-MA and monocytes compared to the control group (<i>P</i> < .05). Proteome quantification identified 1448 proteins differentially expressed between the B-GSA and control groups. Among these, 20 proteins correlated with the levels of <i>t,t</i>-MA in urine. Notably, 4 proteins demonstrated more than a 2-fold down-regulation in the B-GSA group: HBS1-like, non-structural maintenance of chromosomes element 1 homolog, proprotein convertase subtilisin/kexin type 4, and zinc finger protein 658. The KEGG pathway analysis revealed associations with apoptosis, cancer pathways, p53 signaling, and the TNF signaling pathway.</p><p><strong>Conclusion: </strong>The changes in these 4 significant proteins may elucidate the molecular mechanisms underlying benzene toxicity and suggest their potential as biomarkers for benzene poisoning in future assessments.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study.","authors":"Liang-Jen Wang, Ching-Chang Tsai, How-Ran Chao, Sheng-Yu Lee, Chih-Cheng Chen, Sung-Chou Li","doi":"10.1177/11772719241258017","DOIUrl":"10.1177/11772719241258017","url":null,"abstract":"<p><strong>Background: </strong>Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays.</p><p><strong>Objectives: </strong>Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older.</p><p><strong>Design and method: </strong>We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs.</p><p><strong>Results: </strong>When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway.</p><p><strong>Conclusion: </strong>In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression.","authors":"Tarak Dhaouadi, Awatef Riahi, Taïeb Ben Abdallah, Yousr Gorgi, Imen Sfar","doi":"10.1177/11772719241259602","DOIUrl":"10.1177/11772719241259602","url":null,"abstract":"<p><strong>Background: </strong>Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated.</p><p><strong>Objectives: </strong>The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions.</p><p><strong>Design: </strong>This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses.</p><p><strong>Data sources and methods: </strong>An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668.</p><p><strong>Results: </strong>Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all <i>P</i>-values < .001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, <i>P</i> < .001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251-4.748]) than in Asians (OR [95% CI] = 2.537 [1.94-3.318], <i>P</i> = .007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease.</p><p><strong>Conclusion: </strong>This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP.</p><p><strong>Registration: </strong>This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Cytokeratin-18, C-peptide, MHR, and MACK-3 Biomarkers in Metabolic Dysfunction-Associated Fatty Liver Disease After Laparoscopic Sleeve Gastrectomy.","authors":"Mohamed Hany, Hala M Demerdash, Anwar Ashraf Abouelnasr, Bart Torensma","doi":"10.1177/11772719241256496","DOIUrl":"10.1177/11772719241256496","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Consequently, there is a pressing need to develop noninvasive biomarkers for diagnosing and monitoring disease progression.</p><p><strong>Objectives: </strong>This study aimed to evaluate specific biomarkers, including Cytokeratin-18 (CK-18), C-peptide, monocyte to HDL cholesterol ratio (MHR), and MACK-3, in patients with obesity with MAFLD undergoing LSG.</p><p><strong>Design: </strong>A prospective cohort study on patients with obesity before and 6 months after the LSG procedure.</p><p><strong>Methods: </strong>70 patients with obesity with confirmed MAFLD, determined by Transient Elastography (TE), were pre- and 6 months postoperatively tested. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile, ghrelin, leptin, peptide YY, GLP-1, and liver fibrosis scores, including AST/ALT ratio (AAR), Fibrosis-4 index (FIB-4), and BARD Score were tested.</p><p><strong>Results: </strong>BMI significantly decreased in all participants, with a % excess weight loss of 62.0% ± 15.4%. TE measurements revealed a significant postoperative reduction from 100% to 87.1% (<i>P</i> = .006). All selected biomarkers showed significant postoperative improvement-a significant association of CK-18 with MAFLD markers, including AAR, FIB-4, and BARD score, were found. MACK-3 had positive associations with FIB-4. C-peptide and MHR showed no association with MAFLD markers. Furthermore, there was a positive correlation between CK-18 and MACK-3 tests and between C-peptide and CK-18 and MACK-3. Additionally, a receiver operating characteristic (ROC) curve was constructed, with CK-18 performing the best, with an estimated area under the curve of 0.863.</p><p><strong>Conclusion: </strong>Serum CK-18 outperformed other selected biomarkers in predicting and monitoring MAFLD in patients with obesity, suggesting its prospective utility in clinical practice. Further studies are needed to validate the accuracy of the MACK-3 test.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are We Using Ezetimibe As Much As We Should?","authors":"Antonis A Manolis, Theodora A Manolis, Dimitri P Mikhailidis, Antonis S Manolis","doi":"10.1177/11772719241257410","DOIUrl":"10.1177/11772719241257410","url":null,"abstract":"<p><p>Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers.","authors":"Seema Mustafa, Caroline S Jansen, Yash Jani, Sean Evans, Tony Z Zhuang, Jacqueline Brown, Bassel Nazha, Viraj Master, Mehmet Asim Bilen","doi":"10.1177/11772719241254179","DOIUrl":"10.1177/11772719241254179","url":null,"abstract":"<p><p>In the past decade, immune checkpoint inhibitors (ICI) have been approved for treatment of genitourinary malignancies and have revolutionized the treatment landscape of these tumors. However, despite the remarkable success of these therapies in some GU malignancies, many patients' tumors do not respond to these therapies, and others may experience significant side effects, such as immune-related adverse events (iRAEs). Accordingly, biomarkers and improved prognostic tools are critically needed to help predict which patients will respond to ICI, predict and mitigate risk of developing immune-related adverse events, and inform personalized choice of therapy for each patient. Ongoing clinical and preclinical studies continue to provide an increasingly robust understanding of the mechanisms of the response to immunotherapy, which continue to inform biomarker development and validation. Herein, we provide a comprehensive review of biomarkers of the response to immunotherapy in GU tumors and their role in selection of therapy and disease monitoring.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Biomarkers in Type 2 Diabetes Patients With and Without Comorbidities: Insights Into the Role of Hypertension and Cardiovascular Disease.","authors":"Symeon Savvopoulos, Haralampos Hatzikirou, Herbert F Jelinek","doi":"10.1177/11772719231222111","DOIUrl":"https://doi.org/10.1177/11772719231222111","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease.</p><p><strong>Objectives: </strong>Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications.</p><p><strong>Design: </strong>In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively.</p><p><strong>Methods: </strong>Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications.</p><p><strong>Results: </strong>MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant (<i>P</i> < .05) for the transition from prediabetes to t2dm, highlighting importance of mitochondrial involvement. complement component 5a (c5a) is a biomarker associated with disease progression and comorbidities, gsh gssg, monocyte chemoattractant protein-1 (mcp-1), 8-isoprostane being most important biomarkers.</p><p><strong>Conclusions: </strong>Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11069335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Role of Methylated Circulating Tumor DNA in Combination With Pathological Prognostic Factors for Predicting Recurrence of Colorectal Cancer.","authors":"Hiba Al Naji, Jean M Winter, Susanne K Pedersen, Amitesh Roy, Susan E Byrne, Graeme P Young, Erin L Symonds","doi":"10.1177/11772719241232870","DOIUrl":"10.1177/11772719241232870","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) has a high rate of recurrence, in particular for advanced disease, but prognosis based on staging and pathology at surgery can have limited efficacy. The presence of circulating tumor DNA (ctDNA) at diagnosis could be used to improve the prediction for disease recurrence.</p><p><strong>Objectives: </strong>To assess the impact of detecting methylated <i>BCAT1/IKZF1</i> ctDNA at diagnosis in combination with demographic, lifestyle, clinical factors and tumor pathology, to assess predictive value for recurrence.</p><p><strong>Design: </strong>A retrospective cohort study.</p><p><strong>Methods: </strong>The cohort included 180 patients (36 with recurrent CRC), who had undergone complete treatment and surveillance for a minimum of 3 years. Participant clinical details and ctDNA methylated <i>BCAT1</i>/<i>IKZF1</i> results were compared between those with and without recurrence, and cox regression analysis assessed each factor on disease-free survival.</p><p><strong>Results: </strong>Clinical factors independently associated with reduced disease-free survival included nodal involvement (HR = 3.83, 95% CI 1.56-9.43, <i>P</i> = .003), M1 stage (HR = 4.41, 95% CI 1.18-16.45, <i>P</i> = .027), a resection margin less than 2 mm (HR = 4.60, 95% CI 1.19-17.76, <i>P</i> = .027), perineural involvement (HR = 2.50, 95% CI 1.01-6.17, <i>P</i> = .047) and distal tumors (HR = 3.13, 95% CI 1.07-9.18, <i>P</i> = .037). Methylated <i>BCAT1</i>/<i>IKZF1</i> was detected in 51.7% (93/180) of pre-treatment plasma samples. When a positive ctDNA finding was considered in combination with these clinical prognostic factors, there was improved predictive power of recurrence for patients with perineural involvement (HR = 4.44, 95% CI 1.92-10.26, <i>P</i> < .001), and it marginally improved the predictive factor for M1 stage (HR = 7.59, 95% CI 2.30-25.07, <i>P</i> = .001) and distal tumors (HR = 5.04, 95% CI 1.88-13.49, <i>P</i> = .001).</p><p><strong>Conclusions: </strong>Nodal invasion, metastatic disease, distal tumor site, low resection margins and perineural invasion were associated with disease recurrence. Pre-treatment methylated ctDNA measurement can improve the predictive value for recurrence in a subset of patients, particularly those with perineural involvement.</p><p><strong>Registration: </strong>Australian and New Zealand Clinical Trials Registry #12611000318987.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA Expression and Methylation of the <i>RAD51</i>, <i>ATM</i>, <i>ATR</i>, <i>BRCA1</i>, and <i>BRCA2</i> Genes in Gastric Adenocarcinoma.","authors":"Joel Del Bel Pádua, Carolline Fontes Alves Mariano, Alexandre Todorovic Fabro, Fermino Sanches Lizarte Neto, Rogério Lenotti Zuliani, Cláudia Tarcila Gomes Sares, José Sebastião Dos Santos, Ajith Kumar Sankarankutty, Daniela Pretti da Cunha Tirapelli, Vanessa da Silva Silveira, Greice Andreotti de Molfetta, Wilson Araújo da Silva Júnior, Mariângela Ottoboni Brunaldi","doi":"10.1177/11772719231225206","DOIUrl":"10.1177/11772719231225206","url":null,"abstract":"<p><strong>Background: </strong>Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers.</p><p><strong>Objective and design: </strong>This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm.</p><p><strong>Methods: </strong>We evaluated mRNA expression and methylation of <i>RAD51</i>, <i>ATM</i>, <i>ATR</i>, <i>BRCA1</i>, and <i>BRCA2</i> in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features.</p><p><strong>Results: </strong><i>RAD51</i>, <i>ATR</i>, <i>BRCA1</i>, <i>BRCA2</i>, and <i>ATM</i> mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: <i>RAD51</i> with <i>ATR</i> (<i>P</i> = .027), <i>BRCA1</i> (<i>P</i> < .001), and <i>BRCA2</i> (<i>P</i> < .001); <i>ATR</i> with <i>BRCA1</i> (<i>P</i> = .007), and <i>ATM</i> (<i>P</i> = .001); <i>BRCA1</i> with <i>BRCA2</i> (<i>P</i> = 0.001). <i>BRCA1</i> mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, <i>P</i> = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, <i>P</i> = .035). Greater tumoral <i>RAD51</i> mRNA levels correlated with perineural invasion (1.822 vs 0.725, <i>P</i> = .010) and death (1.664 vs 0.929, <i>P</i> = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, <i>P</i> = .032), and no significant correlation for the other markers.</p><p><strong>Conclusions: </strong>Our results suggest <i>RAD51</i>, <i>BRCA1</i>, and <i>BRCA2</i> methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced <i>BRCA1</i> expression participates in disease progression, and show an association between <i>RAD51</i> mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for <i>ATR</i>, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}