Cancer biomarkers : section A of Disease markers最新文献

{"title":"CD133 is an independent predictive and prognostic marker in metastatic breast cancer.","authors":"Ahmed Mubarak Hefni,&nbsp;Ayat Mohammed Sayed,&nbsp;Marwa T Hussien,&nbsp;Ashraf Zeidan Abdalla,&nbsp;Adel Gomaa Gabr","doi":"10.3233/CBM-210539","DOIUrl":"https://doi.org/10.3233/CBM-210539","url":null,"abstract":"<p><strong>Background: </strong>CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer.</p><p><strong>Objectives: </strong>To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics.</p><p><strong>Methods: </strong>One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020.</p><p><strong>Results: </strong>There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012).</p><p><strong>Conclusions: </strong>Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"207-215"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40369860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-96-5p induced NDRG1 deficiency promotes prostate cancer migration and invasion through regulating the NF-κB signaling pathway.","authors":"Zhenpeng Lian,&nbsp;Taihao Chang,&nbsp;Shenfei Ma,&nbsp;Jing Li,&nbsp;Hongtuan Zhang,&nbsp;Xiaoming Wang,&nbsp;Ranlu Liu","doi":"10.3233/CBM-210072","DOIUrl":"https://doi.org/10.3233/CBM-210072","url":null,"abstract":"<p><strong>Objective: </strong>The N-myc downstream-regulated gene 1 (NDRG1) has been discovered as a significant gene in the progression of cancers. However, the regulatory mechanism of NDRG1 remained obscure in prostate cancer (PCa).</p><p><strong>Methods: </strong>The miR-96-5p and NDRG1 expression levels were evaluated in PCa cell lines, prostate tissues, and validated public databases by real-time PCR, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by wound healing and transwell assays in vitro, and mouse xenograft assay in vivo. The candidate pathway regulated by NDRG1 was conducted by the next-generation gene sequencing technique. Immunofluorescence and luciferase assay was used to detect the relation between miR-96-5p, NDRG1, and NF-κB pathway.</p><p><strong>Results: </strong>Overexpressing NDRG1 suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and inhibits metastasis in vivo. Moreover, miR-96-5p contributes to NDRG1 deficiency and promotes PCa cell migration and invasion. Furthermore, NDRG1 loss activates the NF-κB pathway, which stimulates p65 and IKBa phosphorylation and induces EMT in PCa.</p><p><strong>Conclusions: </strong>MiR-96-5p promotes the migration and invasion of PCa by targeting NDRG1 and regulating the NF-κB pathway.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"83-98"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.","authors":"Dae Hoon Lee,&nbsp;E Sun Paik,&nbsp;Young-Jae Cho,&nbsp;Yoo-Young Lee,&nbsp;Bada Lee,&nbsp;Eui Jin Lee,&nbsp;Jung-Joo Choi,&nbsp;Chel-Hun Choi,&nbsp;Sangmin Lee,&nbsp;Jin Woo Choi,&nbsp;Jeong-Won Lee","doi":"10.3233/CBM-210077","DOIUrl":"https://doi.org/10.3233/CBM-210077","url":null,"abstract":"<p><strong>Background: </strong>Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated.</p><p><strong>Objective: </strong>Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC.</p><p><strong>Methods: </strong>Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo.</p><p><strong>Results: </strong>EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel.</p><p><strong>Conclusions: </strong>Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"99-109"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD26 expression on donor harvest as a risk predictive biomarker for developing graft-versus-host disease post-allogeneic hematopoietic stem cell transplantation: A ten-year follow-up study.","authors":"Sachin Punatar,&nbsp;Shruti Kandekar,&nbsp;Navin Khattry,&nbsp;Anant Gokarn,&nbsp;Kumar Prabhash,&nbsp;Ashish Bakshi,&nbsp;Pallavi Rane,&nbsp;Libin Mathew,&nbsp;Shubhada Chiplunkar,&nbsp;Jyoti Kode","doi":"10.3233/CBM-210137","DOIUrl":"https://doi.org/10.3233/CBM-210137","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft-versus-host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long-term transplant outcomes.</p><p><strong>Objective: </strong>Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes.</p><p><strong>Methods: </strong>This study includes donor harvests collected from twenty-three allogeneic donors during period 2008-2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in donor harvest were analyzed using flow cytometry. Percent expression and infused dose of CD26+ and CD34+ cells were evaluated for association with various clinical outcomes.</p><p><strong>Results: </strong>Total 23 healthy donors with median age of 28 years (13 males), and transplant recipients with median age of 24 years (17 males) formed the study cohort. The diagnosis included malignant (n= 13) and non-malignant (n= 10) hematological disorders. Median CD34brCD45lo HSC expression was 0.57% (IQR 0.24-1.03) while median CD26 expression was 19.64% (IQR 8.96-33.56) of all nucleated cells. CD26 expression was associated with donor age (P= 0.037). CD26 percent expression correlated with WBC engraftment (P= 0.015) and with acute GVHD (P= 0.023) whereas infused CD26 cell dose correlated with WBC engraftment (P= 0.004) and risk of CMV reactivation (P= 0.020). There was no statistically significant correlation of either CD26 expression or cell dose with chronic GVHD, EFS or OS.</p><p><strong>Conclusions: </strong>Our findings suggest a role of CD26 expression on human donor harvest as a potential predictor of acute GVHD. This association warrants further exploration.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"17-28"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/CBM-210137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39264293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascites in ovarian cancer: MicroRNA deregulations and their potential roles in ovarian carcinogenesis.","authors":"Luděk Záveský,&nbsp;Eva Jandáková,&nbsp;Vít Weinberger,&nbsp;Veronika Hanzíková,&nbsp;Ondřej Slanař,&nbsp;Milada Kohoutová","doi":"10.3233/CBM-210219","DOIUrl":"https://doi.org/10.3233/CBM-210219","url":null,"abstract":"<p><p>Ovarian cancer comprises the most lethal gynecologic malignancy and is accompanied by the high potential for the incidence of metastasis, recurrence and chemotherapy resistance, often associated with a formation of ascitic fluid. The differentially expressed ascites-derived microRNAs may be linked to ovarian carcinogenesis. The article focuses on a number of miRNAs that share a common expression pattern as determined by independent studies using ascites samples and with regard to their functions and outcomes in experimental and clinical investigations.Let-7b and miR-143 have featured as tumor suppressors in ovarian cancer, which is in line with data on other types of cancer. Although two miRNAs, i.e. miR-26a-5p and miR-145-5p, act principally as tumor suppressor miRNAs, they occasionally exhibit oncogenic roles. The performance of miR-95-3p, upregulated in ascites, is open to debate given the current lack of supportive data on ovarian cancer; however, data on other cancers indicates its probable oncogenic role. Different findings have been reported for miR-182-5p and miR-200c-3p; in addition to their presumed oncogenic roles, contrasting findings have indicated their ambivalent functions. Further research is required for the identification and evaluation of the potential of specific miRNAs in the diagnosis, prediction, treatment and outcomes of ovarian cancer patients.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"1-16"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39407748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E2F1 transcriptionally regulates CCNA2 expression to promote triple negative breast cancer tumorigenicity.","authors":"Yongbin Lu,&nbsp;Fei Su,&nbsp;Hui Yang,&nbsp;Yi Xiao,&nbsp;Xiaobin Zhang,&nbsp;Hongxin Su,&nbsp;Tao Zhang,&nbsp;Yana Bai,&nbsp;Xiaoling Ling","doi":"10.3233/CBM-210149","DOIUrl":"https://doi.org/10.3233/CBM-210149","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. The cell cycle regulator cyclin A2 (CCNA2) plays a role in tumor development. Herein, we explored the role of CCNA2 in TNBC.</p><p><strong>Methods: </strong>We analyzed CCNA2 expression in 15 pairs of TNBC and adjacent tissues and assessed the relationship between CCNA2 expression using the tissue microarray cohort. Furthermore, we used two TNBC cohort datasets to analyze the correlation between CCNA2 and E2F transcription factor 1 (E2F1) and a luciferase reporter to explore their association. Through rescue experiments, we analyzed the effects of E2F1 knockdown on CCNA2 expression and cellular behavior.</p><p><strong>Results: </strong>We found that CCNA2 expression in TNBC was significantly higher than that in adjacent tissues with similar observations in MDA-MB-231 and MDA-MB-468 cells. E2F1 was highly correlated with CCNA2 as observed through bioinformatics analysis (R= 0.80, P< 0.001) and through TNBC tissue verification analysis (R= 0.53, P< 0.001). We determined that E2F1 binds the +677 position within the CCNA2 promoter. Moreover, CCNA2 overexpression increased cell proliferation, invasion, and migration owing to E2F1 upregulation in TNBC.</p><p><strong>Conclusion: </strong>Our data indicate that E2F1 promotes TNBC proliferation and invasion by upregulating CCNA2 expression. E2F1 and CCNA2 are potential candidates that may be targeted for effective TNBC treatment.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"57-70"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/CBM-210149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39292357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Droplet digital polymerase chain reaction for detection and quantification of cell-free DNA TP53 target somatic mutations in oral cancer.","authors":"Li-Han Lin,&nbsp;Hui-Wen Cheng,&nbsp;Chung-Ji Liu","doi":"10.3233/CBM-210275","DOIUrl":"https://doi.org/10.3233/CBM-210275","url":null,"abstract":"<p><strong>Background: </strong>TP53 mutation is a driver mutation of oral carcinogenesis. This study investigated cancerous and cell-free DNA (cfDNA) in patients with oral squamous cell carcinoma (OSCC) to detect the target hotspot somatic mutation of TP53.</p><p><strong>Objective: </strong>TP53 target hotspot mutations were determined in surgically resected primary tumor samples from 107 OSCC patients.</p><p><strong>Methods: </strong>Cancerous and cfDNA samples were examined for mutations through droplet digital polymerase chain reaction (ddPCR) by using mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data.</p><p><strong>Results: </strong>In total, 23 cases had target TP53 mutations in varying degrees. We found that OSCC had relatively low cfDNA shedding, and mutations were at low allele frequencies. Of these 23 cases, 13 had target TP53 mutations in their corresponding cfDNA. Target somatic mutations in cancerous DNA and cfDNA are related to cervical lymph node metastasis. The cfDNA concentration is related to primary tumor size, lymph node metastasis, and OSCC stage.</p><p><strong>Conclusions: </strong>Our results show that the detection of TP53 target somatic mutations in OSCC patients by using ddPCR is technically feasible. Low levels of cfDNA may produce different results between cancerous tissue and cfDNA analyses. Future research on cfDNA may quantify diagnostic biomarkers in the surveillance of OSCC patients.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"29-41"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/CBM-210275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39292359","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":"Analysis of the relationship between the expression of EBV-related antibodies and ET-1 axis in gastric cancer.","authors":"Yan Zhang,&nbsp;Qianqian Zhang,&nbsp;Lin Xu,&nbsp;Weiwen Wang,&nbsp;Hua Xiao,&nbsp;Bing Luo","doi":"10.3233/CBM-220001","DOIUrl":"https://doi.org/10.3233/CBM-220001","url":null,"abstract":"<p><strong>Background and objective: </strong>EBV-associated gastric cancer (EBVaGC) is a distinct subtype of GC, and EBV plays an important role in tumor progress. The standard method to identify EBV-positive tumor is determined by in situ hybridization for EBV-encoded EBERs in tumor tissues. The present study aims to detect the serological expression of EBV-related antibodies and ET-1 axis to provide a noninvasive method for diagnosis of EBVaGC.</p><p><strong>Methods: </strong>The content of EBV-related antibodies and ET-1 axis in preoperative peripheral blood of GC was performed by Chemiluminescence and ELISA assay. The EBV DNA copy number was measured by qRT-PCR.</p><p><strong>Results: </strong>The results showed that the levels of anti-EBV early antigen (EA) IgG, viral capsid antigen (VCA) IgA, nuclear antigen (NA) IgG, and EBV DNA copy number were significantly higher in EBVaGC. The ET-1 axis level was much lower in EBVaGC than EBVnGC.</p><p><strong>Conclusions: </strong>The combined detection of specific anti-EBV antibodies and ET-1 axis might provide new molecular markers for the identification of EBVaGC.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"321-329"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical significance and function of EGFR mutation in TKI treatments of NSCLC patients.","authors":"Hao Ding,&nbsp;Yuxing Chen,&nbsp;Yuanyang Zhao,&nbsp;Li Zhu,&nbsp;Huaying Huang,&nbsp;Chenyang Liu,&nbsp;Feng Zhang,&nbsp;Cunxi Zhang,&nbsp;Cheng Jin","doi":"10.3233/CBM-210281","DOIUrl":"https://doi.org/10.3233/CBM-210281","url":null,"abstract":"<p><strong>Background: </strong>EGFR mutations widely exists in NSCLC patients, which are involved in cancer development.</p><p><strong>Objective: </strong>The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients.</p><p><strong>Methods: </strong>A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation.</p><p><strong>Results: </strong>The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through the PI3K/Akt signaling pathway.</p><p><strong>Conclusions: </strong>The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"119-125"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations.","authors":"Šárka Šestáková,&nbsp;Zdeněk Krejčík,&nbsp;Adam Folta,&nbsp;Ela Cerovská,&nbsp;Cyril Šálek,&nbsp;Michaela Dostálová Merkerová,&nbsp;Pavla Pecherková,&nbsp;Zdeněk Ráčil,&nbsp;Jiří Mayer,&nbsp;Petr Cetkovský,&nbsp;Hana Remešová","doi":"10.3233/CBM-182176","DOIUrl":"https://doi.org/10.3233/CBM-182176","url":null,"abstract":"<p><strong>Background: </strong>Aberrant epigenetic patterns are a hallmark of acute myeloid leukemia (AML). Mutations in profound epigenetic regulators DNMT3A and IDH1/2 often occur concurrently in AML.</p><p><strong>Objectives: </strong>The aim was to analyze DNA methylation, hydroxymethylation and mRNA expression profiles in AML with mutations in DNMT3A and IDH1/2 (individually and in combinations).</p><p><strong>Methods: </strong>Infinium MethylationEPIC BeadChip (Illumina) covering 850,000 CpGs was utilized. The validation of hydroxy-/methylation data was done by pyrosequencing. HumanHT-12 v4 Expression BeadChip (Illumina) was used for expression examination.</p><p><strong>Results: </strong>Hierarchical clustering analysis of DNA hydroxy-/methylation data revealed clusters corresponding to DNMT3A and IDH1/2 mutations and CD34+ healthy controls. Samples with concurrent presence of DNMT3A and IDH1/2 mutations displayed mixed DNA hydroxy-/methylation profile with preferential clustering to healthy controls. Numbers and levels of DNA hydroxymethylation were low. Uniformly hypermethylated loci in AML patients with IDH1/2 mutations were enriched for immune response and apoptosis related genes, among which hypermethylation of granzyme B (GZMB) was found to be associated with inferior overall survival of AML patients (P= 0.035).</p><p><strong>Conclusions: </strong>Distinct molecular background results in specific DNA hydroxy-/methylation profiles in AML. Site-specific DNA hydroxymethylation changes are much less frequent in AML pathogenesis compared to DNA methylation. Methylation levels of enhancer located upstream GZMB gene might contribute to AML prognostication models.</p>","PeriodicalId":520578,"journal":{"name":"Cancer biomarkers : section A of Disease markers","volume":" ","pages":"43-51"},"PeriodicalIF":3.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/CBM-182176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37154152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}