{"title":"Differentiating Latent Tuberculosis from Active Tuberculosis Through Activation Phenotypes and Chemokine Markers HLA-DR, CD38, MCP-1, and RANTES: A Systematic Review and Meta-Analysis.","authors":"Chaimae Kadi, Narjisse Ahmadi, Anass Houdou, Imad El Badisy, Oumnia Bouaddi, Zakaria Mennane, Nouhaila Najimi, Maryam Benlamari, Saber Boutayeb, Mohamed Khalis, Noureddine El Mtili, Fouad Seghrouchni","doi":"10.1177/11772719241312776","DOIUrl":"10.1177/11772719241312776","url":null,"abstract":"<p><strong>Background: </strong>Latent TB infection (LTBI) affects one fourth of the global population. Currently, there is an absence of an optimal strategy for distinguishing between active tuberculosis (aTB) and LTBI. While some researchers have explored cytokines other than interferon-gamma (IFN-γ) as biomarkers, results have shown significant variability in their ability to differentiate between these conditions. This meta-analysis aims to evaluate the performance of activation phenotype and chemokine markers in distinguishing between aTB and LTBI.</p><p><strong>Objectives: </strong>To assess the diagnostic accuracy of specific biomarkers (HLA-DR<sup>+</sup> IFNγ<sup>+</sup>, CD38<sup>+</sup> IFNγ<sup>+</sup>, MCP-1, and RANTES) in differentiating aTB from LTBI.</p><p><strong>Design: </strong>This study was conducted in accordance with the PRISMA guidelines for systematic reviews and meta-analyses of diagnostic studies.</p><p><strong>Data sources and methods: </strong>We conducted a comprehensive search of PubMed, Scopus, Sciences Direct, and Web of Science for primary studies published in English up to 2023. Studies were included if they reported sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for the biomarkers in question. We calculated pooled diagnostic sensitivity, specificity, DOR, and AUC, and used the summary receiver operating characteristic curve (SROC) to summarize the diagnostic performance of each biomarker.</p><p><strong>Results: </strong>Sixteen studies involving 1696 participants were included in the analysis. Among them, 925 individuals were diagnosed with aTB, while 771 were classified as having LTBI. The specificity, sensitivity, DOR, and AUC for CD38<sup>+</sup> IFNγ<sup>+</sup>, HLA-DR<sup>+</sup> IFNγ<sup>+</sup>, RANTES, and MCP-1 were (0.97 [95% CI: 0.72-1.00], 0.90 [95% CI: 0.75-0.96], 291.863, and 0.9432), (0.90 [95% CI: 0.70-0.97], 0.83 [95% CI: 0.63-0.94], 41.819, and 0.8598), (0.68 [95% CI: 0.55-0.79], 0.72 [95% CI: 0.56-0.84], 5.733, and 0.7979), and (0.63 [95% CI: 0.54-0.72], 0.63 [95% CI: 0.50-0.75], 2.892, and 0.7290) respectively.</p><p><strong>Conclusion: </strong>The findings indicate that CD38<sup>+</sup> IFNγ<sup>+</sup> and HLA-DR<sup>+</sup> IFNγ<sup>+</sup> demonstrated the highest diagnostic accuracy. Additional prospective research is necessary to identify the optimal combination of biomarkers to enhance diagnostic accuracy in clinical settings.</p><p><strong>Registration: </strong>This review has been registered on PROSPERO: (CRD42023472091). Available from: https://www.crd.york.ac.uk/prospero/#recordDetails.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719241312776"},"PeriodicalIF":3.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11713980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972594","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":"<i>Helicobacter pylori</i> Seroprevalence in Rheumatoid Arthritis Patients with Interstitial Lung Disease.","authors":"Shomi Oka, Takashi Higuchi, Hiroshi Furukawa, Kota Shimada, Akira Okamoto, Misuzu Fujimori, Atsushi Hashimoto, Akiko Komiya, Koichiro Saisho, Norie Yoshikawa, Masao Katayama, Toshihiro Matsui, Naoshi Fukui, Kiyoshi Migita, Shigeto Tohma","doi":"10.1177/11772719241297171","DOIUrl":"10.1177/11772719241297171","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is complicated with interstitial lung disease (ILD). Gastroesophageal reflux disease is prevented by <i>Helicobacter pylori</i> infection and is a predisposing factor for idiopathic pulmonary fibrosis. However, the prevalence of <i>H. pylori</i> infection in RA patients with ILD has not been sufficiently investigated.</p><p><strong>Objective: </strong>In this study, we analyzed anti-<i>H. pylori</i> antibodies in RA patients with ILD.</p><p><strong>Design: </strong>Case-control observational study.</p><p><strong>Methods: </strong>Anti-<i>H. pylori</i> antibodies were analyzed in the sera of RA patients using a commercially available enzyme-linked immunosorbent assay kit.</p><p><strong>Results: </strong>The positivity of anti-<i>H. pylori</i> antibodies in RA with ILD (<i>n</i> = 30 [18.0%], <i>P</i> = .0227), usual interstitial pneumonia (<i>n</i> = 10 [14.3%], <i>P</i> = .0212), and airway disease (<i>n</i> = 30 [18.0%], <i>P</i> = .0227) was significantly lower than that of RA without chronic lung disease (<i>n</i> = 78 [27.5%]). The positivity of anti-<i>H. pylori</i> antibodies was also lower in RA with chronic lung disease (<i>n</i> = 68 [18.2%], <i>P</i> = .0059). Multiple logistic regression analyses showed that the presence of anti-<i>H. pylori</i> antibodies was independently and protectively associated with chronic lung disease in RA.</p><p><strong>Conclusion: </strong>The seroprevalence of <i>H. pylori</i> was lower in RA with ILD. <i>H. pylori</i> infection prevented ILD in patients with RA by protecting them from gastroesophageal reflux disease.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241297171"},"PeriodicalIF":3.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787418","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}
Biomarker InsightsPub Date : 2024-11-26eCollection Date: 2024-01-01DOI: 10.1177/11772719241296631
Stefan Acosta, Annika Reintam Blaser, Alexandre Nuzzo, Yasmin Soltanzadeh-Naderi, Joel Starkopf, Alastair Forbes, Marko Murruste, Kadri Tamme, Anna-Liisa Voomets, Merli Koitmäe, Miklosh Bala, Zsolt Bodnar, Dumitru Casian, Zaza Demetrashvili, Alan Biloslavo, Virginia Dúran Muñoz-Cruzado, Benjamin Hess, Karri Kase, Mikhail Kirov, Matthias Lindner, Cecilia I Loudet, Dimitrios Damaskos, Martin Björck
{"title":"D-Dimer in Acute Mesenteric Venous Thrombosis: A Prospective Case-Control International Multicenter Study.","authors":"Stefan Acosta, Annika Reintam Blaser, Alexandre Nuzzo, Yasmin Soltanzadeh-Naderi, Joel Starkopf, Alastair Forbes, Marko Murruste, Kadri Tamme, Anna-Liisa Voomets, Merli Koitmäe, Miklosh Bala, Zsolt Bodnar, Dumitru Casian, Zaza Demetrashvili, Alan Biloslavo, Virginia Dúran Muñoz-Cruzado, Benjamin Hess, Karri Kase, Mikhail Kirov, Matthias Lindner, Cecilia I Loudet, Dimitrios Damaskos, Martin Björck","doi":"10.1177/11772719241296631","DOIUrl":"10.1177/11772719241296631","url":null,"abstract":"<p><strong>Background: </strong>Acute mesenteric venous thrombosis (MVT) is rarely suspected as primary diagnosis in emergency departments and still carries an in-hospital mortality rate of above 20%.</p><p><strong>Objectives: </strong>The aim of this study was to find differences in clinical and laboratory markers between patients with acute MVT and a control group of suspected but confirmed as not having any type of acute mesenteric ischaemia (AMI).</p><p><strong>Design: </strong>Data was retrieved from the AMESI (Acute MESenteric Ischaemia) study. This international, multicenter prospective case-control study from 32 sites collected data on patients with suspected AMI during a 10-month period.</p><p><strong>Methods: </strong>Independent factors associated with acute MVT were evaluated in a multivariable logistic regression analysis and expressed as odds ratios (OR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>D-dimer was not significantly higher in MVT (n = 73) compared to non-AMI (n = 287) patients (median 7.0 mg/L vs 4.5 mg/L, <i>P</i> = .092). After entering BMI, atherosclerotic disease, history of venous thromboembolism, CRP, and D-dimer as covariates in a multi-variable logistic regression analysis, absence of atherosclerotic disease (OR 0.096, 95% CI 0.011-0.84; <i>P</i> = .034) and elevated D-dimer (OR 2.59/one SD increment, 95% CI 1.07-6.28; <i>P</i> = .034) were associated with MVT. The discriminative ability of D-dimer for MVT as assessed by area under the curve in the receiver operating characteristics analysis was 0.63 (95% CI 0.49-0.78).</p><p><strong>Conclusion: </strong>Elevated D-dimer was associated with MVT, but the discriminative ability of D-dimer was poor. There is an urgent need to find a more accurate plasma biomarker for this condition.</p><p><strong>Trial registration: </strong>NCT05218863 (registered 19.01.2022).</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241296631"},"PeriodicalIF":3.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733321","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":"Procalcitonin Guided Antibiotic Stewardship.","authors":"Girum Tesfaye Kiya, Elsah Tegene Asefa, Gemeda Abebe, Zeleke Mekonnen","doi":"10.1177/11772719241298197","DOIUrl":"10.1177/11772719241298197","url":null,"abstract":"<p><p>Despite infection and sepsis being a major public health challenge, early detection and timely management are often hindered by several factors. These includes the similarity of clinical presentations between infectious and non-infectious conditisons, as well as limitations of current diagnostic methods such as lengthy turnaround times and low sensitivity. Consequently, there is increasing interest in identifying biomarkers that can quickly and accurately differentiate bacterial sepsis from other inflammatory processes, whether infectious or non-infectious. Procalcitonin has emerged as one of the most extensively studied and utilized biomarkers in managing infection and sepsis, especially within the framework of antibiotic stewardship. This review aims to examine the role of Procalcitonin in guiding antibiotic stewardship. It explores the production and release of procalcitonin and its relevance in the context of infection and sepsis. The discussion focus on the clinical and economic impacts of using procalcitonin to guide the initiation and discontinuation of antibiotics in managing these conditions.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241298197"},"PeriodicalIF":3.4,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669308","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}
Biomarker InsightsPub Date : 2024-11-06eCollection Date: 2024-01-01DOI: 10.1177/11772719241297168
Charbel Feghaly, Rafka Challita, Hanine Bou Hadir, Tala Mobayed, Tarek Al Bitar, Mohammad Harbi, Hala Ghorayeb, Rana El-Hassan, Larry Bodgi
{"title":"Bladder Cancer Treatments in the Age of Personalized Medicine: A Comprehensive Review of Potential Radiosensitivity Biomarkers.","authors":"Charbel Feghaly, Rafka Challita, Hanine Bou Hadir, Tala Mobayed, Tarek Al Bitar, Mohammad Harbi, Hala Ghorayeb, Rana El-Hassan, Larry Bodgi","doi":"10.1177/11772719241297168","DOIUrl":"https://doi.org/10.1177/11772719241297168","url":null,"abstract":"<p><p>Bladder cancer is one of the most frequently diagnosed cancers in men. While cystectomy remains the primary treatment, advances in radiotherapy and chemotherapy have highlighted the value of bladder-preserving strategies, which can also enhance patients' quality of life. Despise these advances, around 20% of patients may still require salvage cystectomy due to tumor radioresistance. This underscores the need to develop radiosensitivity predictive assays. Radiotherapy acts by inducing DNA damage, primarily through DNA double-strand breaks, which can significantly affect treatment outcomes if left unrepaired. In addition to activating DNA repair pathways, the response to radiation also involves the tumor microenvironment, cell death pathways, immune responses and different types of cell death and proliferation receptors. In recent years, personalized medicine, which tailors treatments to individual patients, has gained increasing attention in cancer care. The development of chemo- and radiosensitivity predictive assays has become a key focus of cancer research. Despite the potential impact of such assays on bladder cancer treatment, there is still no reliable test that can help clinicians and informs patients in choosing the best treatment. This review aims to highlight studies that attempted to characterize bladder cancer radiosensitivity and to discuss the potential biomarkers that could be used to develop bladder cancer radiosensitivity predictive assays.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241297168"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606921","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}
Biomarker InsightsPub Date : 2024-11-04eCollection Date: 2024-01-01DOI: 10.1177/11772719241297169
Thuan Duc Lao, Thuy Ai Huyen Le
{"title":"Systematic Analysis and Insights Into the Mutation Spectrum and Ethnic Differences in ATP7B Mutations Associated With Wilson Disease.","authors":"Thuan Duc Lao, Thuy Ai Huyen Le","doi":"10.1177/11772719241297169","DOIUrl":"10.1177/11772719241297169","url":null,"abstract":"<p><strong>Background: </strong><i>ATP7B</i> (ATPase copper transporting beta gene) is constituted of 21 exons, and codes for a 1465 amino acid. The protein of ATP7B plays an key role of copper metabolism. Many previous reports indicated that mutations in <i>ATP7B</i> are well known to cause defective copper transporting copper-transporting ATPase 2 protein leading to the accumulation of copper, resulting the Wilson disease.</p><p><strong>Objectives: </strong>The meta-analysis was performed to comprehensive gain a thorough grasp of the spectrum of genetic variations.</p><p><strong>Design: </strong>A meta-analysis was conducted according to the guiding of PRISMA. aiming to assess the diversity and frequency of mutations in the <i>ATP7B</i> gene, with an emphasis on mutations located within specific exons.</p><p><strong>Data sources and methods: </strong>The dataset of detected mutations within their positions, types as well as nomenclature, were recorded from previous studies (spanning the year from 2013 to 2023). The analysis focused on exon-specific variations and their prevalence across different populations.</p><p><strong>Results: </strong>A total of 40 studies were enrolled into current data analysis. Our comprehensive study revealed a variety of mutations, most notably over 50% of single nucleotide changes described, distributed over the 21 exons of the gene. Focusing on the exon 8, itisplayed the most diversity of mutations, with 18 studies identifying 53 unique variants, the majority of which were missense mutations (81.13%). Additionally, the variations c.2333G>A/T (p.R778Q/L), c.2305A>G (p.M769V), c.2336G>A (p.W779*), and c.2304dupC (p.M769HfsX26) are reported in many populations. The weighted mean of variants' proportion was used to calculate the pooled estimate of these percentages, which were 14.19% for c.2333G>A/T (p.R778Q/L), 2.70% for c.2305A>G (p.M769V), 1.42% for c.2336G>A (p.W779*), and 2.33% for c.2304dupC (p.M769HfsX26).</p><p><strong>Conclusion: </strong>This design demonstrate to identify the spectrum of <i>ATP7B</i> gene's mutations, especially exon 8, offering important insights into the prevalence and significance of exon 8 mutations. Understanding the mutation in the <i>ATP7B</i> gene offers insights into the mechanisms behind WD and guides strategies for diagnosis and treatment.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241297169"},"PeriodicalIF":3.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583743","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}
Biomarker InsightsPub Date : 2024-11-04eCollection Date: 2024-01-01DOI: 10.1177/11772719241296619
Emmanuel Ayitey Tagoe, Jael Acquah Appiah, Pius Agyenim Boateng, Osbourne Quaye, Samuel Bosomprah
{"title":"Decreased Serum Insulin Receptor Messenger RNA Level in <i>H. pylori</i> IgG Seropositive Type 2 Diabetic Patients.","authors":"Emmanuel Ayitey Tagoe, Jael Acquah Appiah, Pius Agyenim Boateng, Osbourne Quaye, Samuel Bosomprah","doi":"10.1177/11772719241296619","DOIUrl":"10.1177/11772719241296619","url":null,"abstract":"<p><strong>Background: </strong>Helicobacter pylori (H. pylori) is a known gastro-intestinal pathogen but implicated in extra-gastric diseases. The relationship between H. pylori infection and type 2 diabetes (T2DM) remains insufficiently elucidated, particularly in terms of molecular mediators such as microRNAs (miRNAs) and messenger RNAs (mRNAs).</p><p><strong>Objective: </strong>We aimed to characterize expression pattern of insulin signalling mRNAs and targeted miRNAs in T2DM patients exposed to H. pylori infection.</p><p><strong>Methods: </strong>We conducted a cross-sectional study among patients diagnosed with type 2 diabetes mellitus and were aged 18 to 60 years. Overnight fasting blood samples were collected and processed for plasma and serum. The plasma samples were used for glucose estimation and the serum used for H. pylori IgG screening. Total RNA was extracted from the serum with commercial kit, and mRNAs and miRNAs quantified by RT-qPCR with specific primers and under predetermined amplification conditions. Clinical data were obtained from medical records of patients.</p><p><strong>Results: </strong>Among 351 patients enrolled, 267 (76.1%) were females, 224 (63.8%) were married, and 79 (22.5%) had tertiary education. Expression level of insulin receptor mRNA was significantly lower in H. pylori positive T2DM patients compared to H. pylori negative (<i>P</i> < .05). There was no evidence of a difference in insulin receptor substrate 1 mRNA level (<i>P</i> > .05). Although not statistically significant, the expression levels of miRNA-222 and miRNA-155 in the patients exposed to <i>H. pylori</i> were higher than that of the unexposed group (<i>P</i> > .05).</p><p><strong>Conclusions: </strong>We found a significantly reduced serum insulin receptor messenger RNA level and higher levels of miRNA-222 and miRNA-155 in H. pylori exposed T2DM patients. The findings suggest a possible role of the infection in insulin signalling alteration in the patients.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241296619"},"PeriodicalIF":3.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583643","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}
Biomarker InsightsPub Date : 2024-10-30eCollection Date: 2024-01-01DOI: 10.1177/11772719241274017
Anne Dietz, Prabal Subedi, Omid Azimzadeh, Lukas Duchrow, Felix Kaestle, Juliane Paetzold, Sarah Katharina Payer, Sabine Hornhardt, Christine von Toerne, Stefanie M Hauck, Bettina Kempkes, Cornelia Kuklik-Roos, Danielle Brandes, Arndt Borkhardt, Simone Moertl, Maria Gomolka
{"title":"The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells.","authors":"Anne Dietz, Prabal Subedi, Omid Azimzadeh, Lukas Duchrow, Felix Kaestle, Juliane Paetzold, Sarah Katharina Payer, Sabine Hornhardt, Christine von Toerne, Stefanie M Hauck, Bettina Kempkes, Cornelia Kuklik-Roos, Danielle Brandes, Arndt Borkhardt, Simone Moertl, Maria Gomolka","doi":"10.1177/11772719241274017","DOIUrl":"10.1177/11772719241274017","url":null,"abstract":"<p><strong>Background: </strong>Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutations in the ATM (mutated ataxia telangiectasia) gene, that cause the rare recessively inherited disease Ataxia telangiectasia (AT). Hallmark features include chromosomal instability and increased sensitivity to ionizing radiation (IR).</p><p><strong>Objectives: </strong>To deepen the molecular understanding of radiosensitivity and to identify potential new markers to predict it, human ATM-mutated and proficient cells were compared on a proteomic level.</p><p><strong>Design: </strong>In this study, we analyzed 3 cell lines from AT patients, with varying radiosensitivity, and 2 cell lines from healthy volunteers, 24 hours and 72 hours post-10 Gy irradiation.</p><p><strong>Methods: </strong>We used label-free mass spectrometry to identify differences in signaling pathways after irradiation in normal and radiosensitive individuals. Cell viability was initially determined by water soluble tetrazolium (WST) assay and DNA damage response was analyzed with 53BP1 repair foci formation along with KRAB-associated protein 1 (KAP1) phosphorylation.</p><p><strong>Results: </strong>Proteomic analysis identified 4028 proteins, which were used in subsequent in silico pathway enrichment analysis to predict affected biological pathways post-IR. In AT cells, networks were heterogeneous at both time points with no common pathway identified. Mitotic cell cycle progress was the most prominent pathway altered after IR in cells from healthy donors. In particular, components of the chromosome passenger complex (INCENP and CDCA8) were significantly downregulated after 72 hours. This could also be verified at the mRNA level.</p><p><strong>Conclusion: </strong>Altogether, the most striking result was that proteins forming the chromosome passenger complex were downregulated after radiation exposure in healthy normosensitive control cells, but not in radiosensitive ATM-deficient cells. Thus, mitosis-associated proteins form an interesting compound to gain insights into the development and prediction of radiosensitivity.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241274017"},"PeriodicalIF":3.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569911","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":"D-dimer as a Predictive Biomarker of Response to Chemotherapy in Patients With Metastatic Breast Cancer.","authors":"Lubana Alkhoder, Maher Salamoon, Maher Saifo, Sulaf Alwassouf","doi":"10.1177/11772719241290704","DOIUrl":"10.1177/11772719241290704","url":null,"abstract":"<p><strong>Background: </strong>Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types.</p><p><strong>Objectives: </strong>This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients.</p><p><strong>Design: </strong>This was a prospective study.</p><p><strong>Methods: </strong>This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy.</p><p><strong>Results: </strong>In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer.</p><p><strong>Conclusion: </strong>D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241290704"},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477480","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}
Biomarker InsightsPub Date : 2024-10-03eCollection Date: 2024-01-01DOI: 10.1177/11772719241287400
Medi Kori, Esra Gov, Kazim Yalcin Arga, Raghu Sinha
{"title":"Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer.","authors":"Medi Kori, Esra Gov, Kazim Yalcin Arga, Raghu Sinha","doi":"10.1177/11772719241287400","DOIUrl":"10.1177/11772719241287400","url":null,"abstract":"<p><strong>Background: </strong>Clinical biomarkers, allow better classification of patients according to their disease risk, prognosis, and/or response to treatment. Although affordable omics-based approaches have paved the way for quicker identification of putative biomarkers, validation of biomarkers is necessary for translation of discoveries into clinical application.</p><p><strong>Objective: </strong>Accordingly, in this study, we emphasize the potential of in silico approaches and have proposed and applied 3 novel sequential in silico pre-clinical validation steps to better identify the biomarkers that are truly desirable for clinical investment.</p><p><strong>Design: </strong>As protein biomarkers are becoming increasingly important in the clinic alongside other molecular biomarkers and lung cancer is the most common cause of cancer-related deaths, we used protein biomarkers for lung cancer as an illustrative example to apply our in silico pre-clinical validation approach.</p><p><strong>Methods: </strong>We collected the reported protein biomarkers for 3 cases (lung adenocarcinoma-LUAD, squamous cell carcinoma-LUSC, and unspecified lung cancer) and evaluated whether the protein biomarkers have cancer altering properties (i.e., act as tumor suppressors or oncoproteins and represent cancer hallmarks), are expressed in body fluids, and can be targeted by FDA-approved drugs.</p><p><strong>Results: </strong>We collected 3008 protein biomarkers for lung cancer, 1189 for LUAD, and 182 for LUSC. Of these protein biomarkers for lung cancer, LUAD, and LUSC, only 28, 25, and 6 protein biomarkers passed the 3 in silico pre-clinical validation steps examined, and of these, only 5 and 2 biomarkers were specific for lung cancer and LUAD, respectively.</p><p><strong>Conclusion: </strong>In this study, we applied our in silico pre-clinical validation approach the protein biomarkers for lung cancer cases. However, this approach can be applied and adapted to all cancer biomarkers. We believe that this approach will greatly facilitate the transition of cancer biomarkers into the clinical phase and offers great potential for future biomarker research.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"19 ","pages":"11772719241287400"},"PeriodicalIF":3.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381986","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}