Molecular and Cellular Probes最新文献

{"title":"Relation of CRP gene variants to altered risk of Helicobacter pylori - associated chronic gastritis: A case-control study in Tunisia","authors":"Mouna Stayoussef ,&nbsp;Sabrina Zidi ,&nbsp;Perizat Kanabekova ,&nbsp;Leila Mouellhi ,&nbsp;Wassim Y. Almawi ,&nbsp;Besma Yaacoubi-Loueslati","doi":"10.1016/j.mcp.2022.101864","DOIUrl":"10.1016/j.mcp.2022.101864","url":null,"abstract":"<div><h3>Background</h3><p>We investigated the association between <span><em>CRP</em></span><span> variants and chronic gastritis in </span><span><em>H. </em><em>pylori</em></span>-infected patients at the allele, genotype, and haplotype levels. This was also assessed according to serum hs-CRP levels.</p></div><div><h3>Methods</h3><p>Study subjects consisted of 77 <em>H. pylori</em>-infected patients and 96 <em>H. pylori</em>-negative controls. Genotyping of the <em>CRP</em> rs1572970, rs876537, rs2794520, rs2808630, rs1130864, rs1417938, rs7553007, and rs4285692 variants were analyzed by real-time PCR.</p></div><div><h3>Results</h3><p><span>Significantly higher MAF and increased risk of chronic gastritis were associated with rs1130864, rs1417938, and rs7553007, which persisted after controlling for key covariates. Significant differences in the genotype distribution of rs1130864, rs1417938, and rs7553007 were also seen between </span><em>H</em>. <em>pylori</em>-infected patients and healthy controls. Increased risk of <em>H. pylori</em>-associated chronic gastritis was associated with carriage of rs1130864 C/T, and more with T/T genotype carriers, as well as with rs1417938 T/A and A/A genotype carriers. Functionally, the distribution of rs1130864 and rs1417938 genotypes were significantly different between <em>H</em>. pylori-infected patients and controls in the low hs-CRP (&lt;6 mg/L) group. CRP haplotype analysis identified Block 1 (rs1572970, rs876537, rs2794520), and Block 2 (rs2808630, rs1130864, rs1417938) associated with <em>H. pylori</em> infection. Haplotypes ACC (Block 1) and TTA and TTT (Block 2) were positively associated with <em>H. pylori</em>-associated chronic gastritis with low hs-CRP levels.</p></div><div><h3>Conclusion</h3><p><span>Altered serum levels of hs-CRP, stemming in part from the presence of specific genetic variants in </span><em>CRP</em> gene, modulate the risk of <em>H. pylori</em> infection.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10504410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression","authors":"Zekiye Altan,&nbsp;Yunus Sahin","doi":"10.1016/j.mcp.2022.101866","DOIUrl":"10.1016/j.mcp.2022.101866","url":null,"abstract":"<div><h3>Background</h3><p>Pancreatic cancer<span> (PC) is an insidious cancer that is commonly diagnosed in advanced stages. Therefore, it is necessary to understand PC-related mechanisms in order to discover new and reliable diagnostic biomarkers. It is known that miRNAs<span> play a crucial role in carcinogenesis by targeting mRNAs. In this study we aimed to explore interaction between downregulated miR-203 and its upregulated target DUSP5 in PC.</span></span></p></div><div><h3>Methods</h3><p>Using bioinformatics approaches we identified the DUSP5 as a direct target gene of miR-203 and detected potential binding sites between miR-203 and DUSP5. Additionally, we evaluated subcellular location, expression level and prognostic value of DUSP5 in PC through using various bioinformatics tools. To investigate the relationship between miR-203 and DUSP5, we increased the expression levels of miR-203 by transfecting miR-203 mimics into the pancreatic cancer cell line, PANC-1. Finally, MTT, wound healing, and colony formation assays were performed to determine effect of overexpressed miR-203 on proliferation and migration of PANC-1 cells.</p></div><div><h3>Results</h3><p>We found that expression level of DUSP5 in pancreas tissue<span> was one of the lowest tissue expression among all normal human tissue types. In addition, DUSP5 expression was upregulated both PC tissues and cell line and associated with poor overall survival in PC. Overexpression of miR-203 significantly downregulated expression level of DUSP5 and remarkably suppressed proliferation, migration and colony formation ability of PANC-1 cells.</span></p></div><div><h3>Conclusions</h3><p>These findings suggest that miR-203 restrains proliferation and migration of PC cells by regulating oncogenic activity of DUSP5 in PC, thereby could be novel candidate biomarkers for PC diagnosis and treatment.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expression of long non-coding RNA LINC01389, LINC00365, RP11-138J23.1, and RP11-354K4.2 in gastric cancer and their impacts on EMT","authors":"Negin Taghehchian ,&nbsp;Moein Farshchian ,&nbsp;Reihaneh Alsadat Mahmoudian ,&nbsp;Ahmad Asoodeh ,&nbsp;Mohammad Reza Abbaszadegan","doi":"10.1016/j.mcp.2022.101869","DOIUrl":"10.1016/j.mcp.2022.101869","url":null,"abstract":"<div><h3>Background</h3><p>Epithelial cancers acquire the epithelial to mesenchymal transition<span> (EMT), which leads tumor cells to invade and metastasize to adjacent and distant tissues. The mechanisms involved in EMT phenotype are controlled by numerous markers as well as signalling pathways. Recently, long non-coding RNAs (lncRNAs) were introduced that play the regulatory role in EMT via crosstalk with EMT-related transcription factors and signalling pathways. The present study aimed to investigate the expression of four lncRNAs in human GC and elucidate their probable role in EMT procedure and the pathogenesis of gastric cancer (GC).</span></p></div><div><h3>Methods</h3><p>The expression profile of lncRNAs (<em>LINC01389, LINC00365, RP11-138J23.1</em>, and <em>RP11-354K4.2</em>) and mRNAs (<em>TWIST1</em>, <span><em>MMP13</em></span>, <em>MAML1</em>, <em>CD44s</em>, and <span><em>SALL4</em></span>) between eighty-three GC and adjacent non-cancerous tissues were assessed by quantitative real-time PCR.</p></div><div><h3>Results</h3><p>The significant downregulation of <em>LINC00365</em> (66.3%) and <em>RP11-354K4.2</em> (62.7%) were observed in GC samples; while the upregulation of <em>LINC01389, RP11-138J23.1</em>, <em>TWIST1</em>, <em>MMP13</em>, <em>MAML1</em>, <em>CD44s</em>, and <em>SALL4</em> were found in 67.5%, 45.8%, 56.6%, 44.6%, 59%, 55.4%, and 62.7% tumors samples at the mRNA level, respectively. Dysregulation of these lncRNAs and EMT-related markers was significantly related to each other in a variety of clinicopathological features of patients (<em>P</em> &lt; 0.05), indicating positive correlations between <em>LINC01389, LINC00365, RP11-138J23.1</em>, and <em>RP11-354K4.2</em> with EMT status in GC.</p></div><div><h3>Conclusion</h3><p>These EMT-regulating lncRNAs may play a key role in transforming gastric epithelial to mesenchymal phenotype and can be novel therapeutic targets for GC. Our results highlight the importance of discovering new lncRNAs involved in gastric carcinogenesis. Detailed molecular mechanisms of these noncoding-coding markers in GC are urgently required.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-intuitive trends of fetal fraction development related to gestational age and fetal gender, and their practical implications for non-invasive prenatal testing","authors":"Natalia Forgacova ,&nbsp;Juraj Gazdarica ,&nbsp;Jaroslav Budis ,&nbsp;Marcel Kucharik ,&nbsp;Martina Sekelska ,&nbsp;Tomas Szemes","doi":"10.1016/j.mcp.2022.101870","DOIUrl":"10.1016/j.mcp.2022.101870","url":null,"abstract":"<div><p>Discovery of fetal cell-free DNA fragments in maternal blood revolutionized prenatal diagnostics. Although non-invasive prenatal testing (NIPT) is already a matured screening test with high specificity and sensitivity, the accurate estimation of the proportion of fetal fragments, called fetal fraction, is crucial to avoid false-negative results. In this study, we collected 6999 samples from women undergoing NIPT testing with a single male fetus to demonstrate the influence of fetal fraction by the maternal and fetal characteristics. We show several fetal fraction discrepancies that contradict the generally presented conventional view. At first, the fetal fraction is not consistently rising with the maturity of the fetus due to a drop in 15 weeks of maturation. Secondly, the male samples have a lower fetal fraction than female fetuses, arguably due to the smaller gonosomal chromosomes. Finally, we discuss not only the possible reasons why this inconsistency exists but we also outline why these differences have not yet been identified and published. We demonstrate two non-intuitive trends to better comprehend the fetal fraction development and more precise selection of patients with sufficient fetal fraction for accurate testing.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850822000810/pdfft?md5=0334ccfdc49c29ae1552bd6907324478&pid=1-s2.0-S0890850822000810-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10448062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients","authors":"Beáta Soltész ,&nbsp;Ondrej Pös ,&nbsp;Zuzana Wlachovska ,&nbsp;Jaroslav Budis ,&nbsp;Rastislav Hekel ,&nbsp;Lucia Strieskova ,&nbsp;Jana Bozenka Liptak ,&nbsp;Werner Krampl ,&nbsp;Jakub Styk ,&nbsp;Nikolett Németh ,&nbsp;Judit Sz Keserű ,&nbsp;Adrienn Jenei ,&nbsp;Gergely Buglyó ,&nbsp;Álmos Klekner ,&nbsp;Bálint Nagy ,&nbsp;Tomas Szemes","doi":"10.1016/j.mcp.2022.101875","DOIUrl":"10.1016/j.mcp.2022.101875","url":null,"abstract":"<div><p>Glioblastoma<span> is the most common malignant tumor of the central nervous system<span><span><span> (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial </span>DNA may serve as biomarkers. As the brain is difficult to access, analysis of mitochondria directly from the </span>brain tissue<span> represents a challenge. Exosome<span> analysis is an alternative (still poorly explored) approach to investigate molecular changes in CNS tumors.</span></span></span></span></p><p><span>We analyzed brain tissue DNA and plasma-derived exosomal DNA (exoDNA) of 44 glioblastoma patients and 40 control individuals. Quantitative real-time PCR was performed to determine mtDNA copy numbers and the Kruskal-Wallis and Mann-Whitney </span><em>U</em><span> test were used for statistical analysis of data. Subsequently, sequencing libraries were prepared and sequenced on the MiSeq platform to identify mtDNA point mutations.</span></p><p>Tissue mtDNA copy number was different among controls and patients in multiple comparisons. A similar tendency was detected in exosomes. Based on NGS analysis, several mtDNA point mutations showed slightly different frequencies between cases and controls, but the clinical relevance of these observations is difficult to assess and likely less than that of overall mtDNA copy number changes. Allele frequencies of variants were used to determine the level of heteroplasmy (found to be higher in exo-mtDNA of control individuals).</p><p>Despite the suggested potential, the use of such biomarkers for the screening and/or diagnosis of glioblastomas is still limited, thus further studies are needed.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10814196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The measurement of NRF2 and TP53 in blood expects radiotherapeutic sensitivity in patients with esophageal cancer","authors":"Huiqin Xu ,&nbsp;Jinchang Wu ,&nbsp;Lansheng Zhang ,&nbsp;yang Li ,&nbsp;Liyan Gao ,&nbsp;Yufeng Cheng","doi":"10.1016/j.mcp.2022.101860","DOIUrl":"10.1016/j.mcp.2022.101860","url":null,"abstract":"<div><h3>Objective</h3><p>This study investigates the relationship between the mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and Tumor protein p53 (TP53) in circulating tumor cells (CTC) and sensitivity to radiotherapy in patients with esophageal cancer. To investigate the relationship between cytokines IL-6, CD8⁺, and NRF2 during patient treatment and their predictive role for treatment.</p></div><div><h3>Methods</h3><p>Radiosensitivity was assessed by measuring a morphological or functional change in the tumor in response to ionizing radiation. Fasting venous anticoagulated blood (EDTA anticoagulation) was drawn from patients, and the Trizol-chloroform two-step method was used for RNA extraction. Data were collected from 45 patients admitted with radiotherapy alone from January 2018 to December 2021. The expression levels of NRF2mRNA (Messenger Ribose Nucleic Acid) and TP53mRNA in CTCs were detected by reverse transcription-polymerase chain reaction (RT-PCR). Pre- and post-treatment changes in IL-6 and CD8⁺ were recorded. The correlation between their expression level and the clinical stage, radiotherapy sensitivity, and efficacy of patients was analyzed.</p></div><div><h3>Results</h3><p>Twenty-six cases were sensitive to radiotherapy, and 19 were resistant, for a radiotherapy sensitivity rate of 58.8%. NRF2mRNA and TP53mRNA values increased in 19 radiotherapy-resistant patients and decreased in 26 radiotherapy-sensitive patients compared with those before radiotherapy (P = 0.001, P＜0.05). The ΔCT values of NRF2mRNA and TP53mRNA before treatment were moderately correlated with prognosis (P &lt; 0.002). Inflammatory cytokine IL-6 was elevated in 22 of 45 patients after radiation, P = 0.04. NRF2 mRNA level was consistently elevated with CD8⁺ in 10 patients, P = 0.02.</p></div><div><h3>Conclusions</h3><p>The expression of NRF2mRNA and TP53mRNA in the CTCs found in the peripheral blood of patients with esophageal squamous carcinoma was significantly associated with the sensitivity to radiotherapy. NRF2 mRNA level was consistently elevated with CD8⁺ and IL-6 in patients.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850822000718/pdfft?md5=b3e5fd5b7015b3115ac15e6812bde043&pid=1-s2.0-S0890850822000718-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The therapeutical effects of damage-specific stress induced exosomes on the cisplatin nephrotoxicity IN VIVO","authors":"Eser Oz Oyar ,&nbsp;Aysegul Aciksari ,&nbsp;Burcu Azak Pazarlar ,&nbsp;Cansu Bilister Egilmez ,&nbsp;Gokhan Duruksu ,&nbsp;Selenay Furat Rencber ,&nbsp;Melda Yardimoglu Yilmaz ,&nbsp;Ahmet Ozturk ,&nbsp;Yusufhan Yazir","doi":"10.1016/j.mcp.2022.101861","DOIUrl":"10.1016/j.mcp.2022.101861","url":null,"abstract":"<div><p><span>Cisplatin is one of the metal containing </span>drugs<span><span> for the solid cancer treatments. However, its side-effects limit its application in the cancer treatment<span><span>. Stem cell therapy is a promising treatment for the tissue damage caused by the chemotherapeutic agents, like cisplatin. </span>Exosomes secreted by </span></span>mesenchymal stem cells<span><span><span> (MSCs) could be used for cell-free regenerative treatment, but their potency and reproducibility are questionable. In this study, the microenvironment of the renal tubular epithelial cells was mimicked by coculture of endothelial-, renal proximal tubule epithelial- and fibroblast cells. Cisplatin was applied to this tricell culture model, and the secreted rescue signals were collected and used to induce MSCs. From these stress-induced MSCs, the (stress-induced) exosomes were collected and used for the cell-free therapeutic treatment of cisplatin-treated rats with </span>acute kidney injury<span>. The composition of the stress-induces exosomes was compared with the non-induced exosomes and found that the expression of some critical factors for cell proliferation, repair mechanism and </span></span>oxidative stress<span> was improved. The cisplatin-damaged renal tissue showed substantial recovery after the treatment with stress-induced exosomes compared to the treatment with non-induced exosomes. Although, the non-induced exosomes showed their activity mostly as cytoprotective, the induced exosomes further involved actively in the tissue regeneration, like MSCs.</span></span></span></p><p>It was shown that the exosomes could be reprogrammed to improve their therapeutic effect to be used in cell-free regenerative medicine. Further, cisplatin-induced tissue damage in the kidney might be effectively prevented and used for tissue regeneration by use of induced exosomes generated for a particular damage.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating metabolites in the early stage of breast cancer were not related to cancer stage or subtypes but associated with ki67 level. Promising statistical discrimination from controls","authors":"Eva Baranovicova ,&nbsp;Peter Racay ,&nbsp;Pavol Zubor ,&nbsp;Marek Smolar ,&nbsp;Eva Kudelova ,&nbsp;Erika Halasova ,&nbsp;Dana Dvorska ,&nbsp;Zuzana Dankova","doi":"10.1016/j.mcp.2022.101862","DOIUrl":"10.1016/j.mcp.2022.101862","url":null,"abstract":"<div><p>It was documented that the presence of malignancy in an organism causes metabolomic alterations in blood plasma which applies also to breast cancer. Breast cancer is a heterogeneous disease and there are only limited known relations of plasma metabolomic signatures with the tumour characteristics in early BC and knowing them would be of great advantage in noninvasive diagnostics. In this study, we focused on the metabolic alterations in early BC in blood plasma with the aim to identify metabolomic characteristics of BC subtypes. We used 50 early BC patients (FIGO stage I and II), where no additional metabolomic changes from metastatically changed remote organs were to be expected. We compared plasma levels of metabolites against controls and among various molecular and histological BC subtypes. BC patients showed decreased plasma levels of branched-chain amino acids BCAAs (and related keto-acids), histidine pyruvate and alanine balanced with an increased level of 3-hydroxybutyrate. The levels of circulating metabolites were not related to BC molecular subtypes (luminal A/luminal B), histological finding or grade, eventually stage, which indicate that in early BC, the BC patients share common metabolomics fingerprint in blood plasma independent of grade, stage or molecular subtype of BC. We observed statistically significant correlations between tumour proliferation marker Ki-67 level and circulating metabolites: alanine, citrate, tyrosine, glutamine, histidine and proline. This may point out the metabolites those levels could be associated with tumour growth, and conversely, the rate of tumour proliferation could be potentially estimated from plasma metabolites. When analyzing metabolomic changes in BC, we concluded that some of them could be associated with the metabolomic features of cancer cells, but the other observed alterations in blood plasma are the results of the complex mutual biochemical pathways in the comprehensive inter-organ metabolic exchange and communication. In the end, statistical discrimination against controls performed with AUC &gt;0.91 showed the very promising potential of plasma metabolomics in the search for biomarkers for oncologic diseases.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850822000731/pdfft?md5=9796eea58ccaeab8dc304c88036ef14c&pid=1-s2.0-S0890850822000731-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A method for early diagnosis of lung cancer from tumor originated DNA fragments using plasma cfDNA methylome and fragmentome profiles","authors":"Yeo Jin Kim ,&nbsp;Hahyeon Jeon ,&nbsp;Sungwon Jeon ,&nbsp;Sung-Hun Lee ,&nbsp;Changjae Kim ,&nbsp;Ji-Hye Ahn ,&nbsp;Hyojin Um ,&nbsp;Yeong Ju Woo ,&nbsp;Seong-ho Jeong ,&nbsp;Yeonkyung Kim ,&nbsp;Ha-Young Park ,&nbsp;Hyung-Joo Oh ,&nbsp;Hyun-Ju Cho ,&nbsp;Jin-Han Bae ,&nbsp;Ji-Hoon Kim ,&nbsp;Seolbin An ,&nbsp;Sung-Bong Kang ,&nbsp;Sungwoong Jho ,&nbsp;Orsolya Biro ,&nbsp;David Kis ,&nbsp;In-Jae Oh","doi":"10.1016/j.mcp.2022.101873","DOIUrl":"10.1016/j.mcp.2022.101873","url":null,"abstract":"<div><p><span><span><span>Early detection is critical for minimizing mortality from cancer. Plasma cell-free DNA (cfDNA) contains the signatures of tumor DNA, allowing us to quantify the signature and diagnose early-stage tumors. Here, we report a novel tumor fragment quantification method, TOF (Tumor Originated Fragment) for the diagnosis of lung cancer by quantifying and analyzing both the plasma </span>cfDNA methylation patterns and fragmentomic signatures. TOF utilizes the amount of </span>ctDNA<span> predicted from the methylation density information of each cfDNA read mapped on 6243 lung-tumor-specific CpG markers. The 6243 tumor-specific markers were derived from lung tumor tissues by comparing them with corresponding normal tissues and healthy blood from public methylation data. TOF also utilizes two cfDNA fragmentomic signatures: 1) the short fragment ratio, and 2) the 5′ end-motif profile. We used 298 plasma samples to analyze cfDNA signatures using enzymatic methyl-sequencing data from 201 lung cancer patients and 97 healthy controls. The TOF score showed 0.98 of the area under the curve in correctly classifying lung cancer from normal samples. The TOF score resolution was high enough to clearly differentiate even the early-stage non-small cell lung cancer patients from the healthy controls. The same was true for </span></span>small cell lung cancer patients.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10814195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone H3 K27 alterations in central nervous system tumours: Challenges and alternative diagnostic approaches","authors":"Nour Kurdi,&nbsp;Attila Mokanszki,&nbsp;Gabor Mehes,&nbsp;Judit Bedekovics","doi":"10.1016/j.mcp.2022.101876","DOIUrl":"10.1016/j.mcp.2022.101876","url":null,"abstract":"<div><p><span><span><span><span>Upon the discovery of frequent oncogenic histone alterations in </span>paediatric<span> diffuse high-grade gliomas, the epigenetic and transcriptional landscapes of tumours have become increasingly important aspects of diagnostic and prognostic analysis. The replacement of lysine 27 with </span></span>methionine<span> in H3 histone<span> variants - H3 p.K28M (K27M) - was the first reported histone mutation associated with human malignancies<span>, seen in up to 80% of paediatric diffuse midline gliomas. This discovery contributed to the updated 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumours in which paediatric diffuse high-grade gliomas were classified into molecular-based categories. Therefore, molecular analysis of tumour cells has become increasingly necessary for determining disease prognosis and potential therapeutic strategies. Although detection of histone alterations is crucial for the diagnosis of specific glioma subtypes, several studies have identified them in other CNS tumours, which may be misleading during routine diagnostic work. While traditional biopsies remain the standard for diagnosis of gliomas, they pose a high risk for </span></span></span></span>surgical complications<span> and patient morbidity. Consequently, this review highlights the importance of the H3 K27-alterations in paediatric gliomas and several other CNS tumours. We also discuss the potential of liquid biopsies as a minimally invasive and highly effective alternative for confirming the diagnosis and potential targeted </span></span>epigenetic therapies which may improve the survival of patients.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10448319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}