A. Druy, G. Tsaur, E. Shorikov, G. Tytgat, L. Fechina
{"title":"Suppressed miR-128-3p combined with TERT overexpression predicts dismal outcomes for neuroblastoma.","authors":"A. Druy, G. Tsaur, E. Shorikov, G. Tytgat, L. Fechina","doi":"10.3233/CBM-210414","DOIUrl":"https://doi.org/10.3233/CBM-210414","url":null,"abstract":"BACKGROUND\u0000Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression.\u0000\u0000\u0000OBJECTIVE\u0000The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma.\u0000\u0000\u0000METHODS\u0000RNA samples isolated from fresh-frozen tumor specimens (n= 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months.\u0000\u0000\u0000RESULTS\u0000Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p= 0.027, TL =-2.32 log10 and p= 0.080, TL =-1.33 log10, respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT/normal miR-128-3p expression and normal TERT/reduced miR-128-3p expression were 0.74 ± 0.08 and 0.60 ± 0.16, respectively. The patients with elevated TERT/reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 ± 0.16 compared with 0.91 ± 0.06 for the patients with unaltered levels of both transcripts (p< 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 ± 0.08, 0.40 ± 0.16, 0.60 ± 0.16 and 0.09 ± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS.\u0000\u0000\u0000CONCLUSIONS\u0000Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75462712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. H. Kim, Yuna Youn, Jong-chan Lee, Jaihwan Kim, J. Ryu, Jin-Hyeok Hwang
{"title":"Downregulation of ASF1B inhibits tumor progression and enhances efficacy of cisplatin in pancreatic cancer.","authors":"J. H. Kim, Yuna Youn, Jong-chan Lee, Jaihwan Kim, J. Ryu, Jin-Hyeok Hwang","doi":"10.3233/cbm-210490","DOIUrl":"https://doi.org/10.3233/cbm-210490","url":null,"abstract":"Pancreatic cancer is an aggressive and lethal cancer with the highest mortality rate. Hence, the development of new targeting and innovative treatment strategies is needed. Recent studies reported that the histone chaperone anti-silencing function 1B (ASF1B) can be used as a diagnosis and prognosis cancer biomarker. However, functional studies of ASF1B in pancreatic cancer have not been performed. This study compared expression levels of ASF1B in pancreatic cancer specimens with those of normal tissues using publicly available online databases. We found that ASF1B was commonly overexpressed in pancreatic cancer specimens, which is associated with poor prognosis. ASF1B downregulation in pancreatic cancer cells reduced their colony formation, proliferation, migration, and invasion abilities, and inhibited MMP9 activity. Furthermore, ASF1B expression downregulation increased cell cycle S-phase arrest and DNA damage though activation of the checkpoint kinases Chk1 and Chk2 pathways. Additionally, increased caspase (caspases-3 and -9) activation and PARP cleavage led to enhanced caspase-dependent apoptosis and improved cisplatin sensitivity. Collectively, our results indicate that ASF1B may serve as a potential biomarker of pancreatic cancer and a novel therapeutic target.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74514572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression pattern and prognostic significance of CDKs in breast cancer: An integrated bioinformatic study.","authors":"Umar Mehraj, Shazia Sofi, B. Alshehri, M. A. Mir","doi":"10.3233/cbm-210186","DOIUrl":"https://doi.org/10.3233/cbm-210186","url":null,"abstract":"BACKGROUND\u0000Globally, breast cancer (BC) has become one of the most prevalent malignancies and the leading cause of tumor-related deaths among women. Dysregulation of the cell cycle is a well-known hallmark of cancer development and metastasis. CDKs are essential components of the cell-cycle regulatory system with aberrant expression in a variety of cancers, including BC. In the development of targeted cancer treatment, reestablishing the regulation of the cell cycle by modulation of CDKs has emerged as a promising approach.\u0000\u0000\u0000METHODS\u0000Herein, we used a bioinformatic approach to assess the expression pattern, prognostic and diagnostic importance, and clinical relevance of CDKs in BC. Additionally, we conducted a functional enrichment analysis of deregulated CDKs using the STRING and KEGG databases to delineate the role of CDKs in breast tumorigenesis.\u0000\u0000\u0000RESULTS\u0000Gene expression analysis revealed substantial deregulation of CDKs in BC, with CDK1, CDK11A, and CDK18 showing a fold change of >± 1.5. Also, metastatic tumors showed high expression of CDK1 in the single cell RNA sequencing analysis of primary and metastatic breast tumors. Additionally, it was found that dysregulated CDK expression affects overall survival (OS) and relapse-free survival (RFS) of BC patients.\u0000\u0000\u0000CONCLUSION\u0000The study's multimodal analytical methodologies imply that modulating CDKs for BC treatment is a promising approach.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84697944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasmine Abouleila, Ahmed Ali, Keiko Masuda, A. Mashaghi, Yoshihiro Shimizu
{"title":"Capillary microsampling-based single-cell metabolomics by mass spectrometry and its applications in medicine and drug discovery.","authors":"Yasmine Abouleila, Ahmed Ali, Keiko Masuda, A. Mashaghi, Yoshihiro Shimizu","doi":"10.3233/cbm-210184","DOIUrl":"https://doi.org/10.3233/cbm-210184","url":null,"abstract":"Characterization of cellular metabolic states is a technical challenge in biomedicine. Cellular heterogeneity caused by inherent diversity in expression of metabolic enzymes or due to sensitivity of metabolic reactions to perturbations, necessitates single cell analysis of metabolism. Heterogeneity is typically seen in cancer and thus, single-cell metabolomics is expectedly useful in studying cancer progression, metastasis, and variations in cancer drug response. However, low sample volumes and analyte concentrations limit detection of critically important metabolites. Capillary microsampling-based mass spectrometry approaches are emerging as a promising solution for achieving single-cell omics. Herein, we focus on the recent advances in capillary microsampling-based mass spectrometry techniques for single-cell metabolomics. We discuss recent technical developments and applications to cancer medicine and drug discovery.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79778586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeted proteomics for cancer biomarker verification and validation.","authors":"Seiryo Ogata, Takeshi Masuda, S. Ito, S. Ohtsuki","doi":"10.3233/cbm-210218","DOIUrl":"https://doi.org/10.3233/cbm-210218","url":null,"abstract":"Targeted proteomics is a method that measures the amount of target proteins via liquid chromatography-tandem mass spectrometry and is used to verify and validate the candidate cancer biomarker proteins. Compared with antibody-based quantification methods such as ELISA, targeted proteomics enables rapid method development, simultaneous measurement of multiple proteins, and high-specificity detection of modifications. Moreover, by spiking the internal standard peptide, targeted proteomics detects the absolute amounts of marker proteins, which is essential for determining the cut-off values for diagnosis and thus for multi-institutional validation. With these unique features, targeted proteomics can seamlessly transfer cancer biomarker candidate proteins from the discovery phase to the verification and validation phases, thereby resulting in an accelerated cancer biomarker pipeline. Furthermore, understanding the basic principles, advantages, and disadvantages is necessary to effectively utilize targeted proteomics in cancer biomarker pipelines. This review aimed to introduce the technical principles of targeted proteomics for cancer biomarker verification and validation.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89768728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Crichton, L. Cinquini, H. Kincaid, A. Mahabal, A. Altinok, K. Anton, M. Colbert, S. Kelly, D. Liu, C. Patriotis, S. Lombeyda, S. Srivastava
{"title":"From space to biomedicine: Enabling biomarker data science in the cloud.","authors":"D. Crichton, L. Cinquini, H. Kincaid, A. Mahabal, A. Altinok, K. Anton, M. Colbert, S. Kelly, D. Liu, C. Patriotis, S. Lombeyda, S. Srivastava","doi":"10.3233/cbm-210350","DOIUrl":"https://doi.org/10.3233/cbm-210350","url":null,"abstract":"NASA's Jet Propulsion Laboratory (JPL) is advancing research capabilities for data science with two of the National Cancer Institute's major research programs, the Early Detection Research Network (EDRN) and the Molecular and Cellular Characterization of Screen-Detected Lesions (MCL), by enabling data-driven discovery for cancer biomarker research. The research team pioneered a national data science ecosystem for cancer biomarker research to capture, process, manage, share, and analyze data across multiple research centers. By collaborating on software and data-driven methods developed for space and earth science research, the biomarker research community is heavily leveraging similar capabilities to support the data and computational demands to analyze research data. This includes linking diverse data from clinical phenotypes to imaging to genomics. The data science infrastructure captures and links data from over 1600 annotations of cancer biomarkers to terabytes of analysis results on the cloud in a biomarker data commons known as \"LabCAS\". As the data increases in size, it is critical that automated approaches be developed to \"plug\" laboratories and instruments into a data science infrastructure to systematically capture and analyze data directly. This includes the application of artificial intelligence and machine learning to automate annotation and scale science analysis.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86191959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Pérez-Morales, Hong Lu, W. Mu, I. Tunali, T. Kutuk, S. Eschrich, Y. Balagurunathan, R. Gillies, M. Schabath
{"title":"Volume doubling time and radiomic features predict tumor behavior of screen-detected lung cancers.","authors":"J. Pérez-Morales, Hong Lu, W. Mu, I. Tunali, T. Kutuk, S. Eschrich, Y. Balagurunathan, R. Gillies, M. Schabath","doi":"10.3233/cbm-210194","DOIUrl":"https://doi.org/10.3233/cbm-210194","url":null,"abstract":"BACKGROUND\u0000Image-based biomarkers could have translational implications by characterizing tumor behavior of lung cancers diagnosed during lung cancer screening. In this study, peritumoral and intratumoral radiomics and volume doubling time (VDT) were used to identify high-risk subsets of lung patients diagnosed in lung cancer screening that are associated with poor survival outcomes.\u0000\u0000\u0000METHODS\u0000Data and images were acquired from the National Lung Screening Trial. VDT was calculated between two consequent screening intervals approximately 1 year apart; peritumoral and intratumoral radiomics were extracted from the baseline screen. Overall survival (OS) was the main endpoint. Classification and Regression Tree analyses identified the most predictive covariates to classify patient outcomes.\u0000\u0000\u0000RESULTS\u0000Decision tree analysis stratified patients into three risk-groups (low, intermediate, and high) based on VDT and one radiomic feature (compactness). High-risk patients had extremely poor survival outcomes (hazard ratio [HR] = 8.15; 25% 5-year OS) versus low-risk patients (HR = 1.00; 83.3% 5-year OS). Among early-stage lung cancers, high-risk patients had poor survival outcomes (HR = 9.07; 44.4% 5-year OS) versus the low-risk group (HR = 1.00; 90.9% 5-year OS). For VDT, the decision tree analysis identified a novel cut-point of 279 days and using this cut-point VDT alone discriminated between aggressive (HR = 4.18; 45% 5-year OS) versus indolent/low-risk cancers (HR = 1.00; 82.8% 5-year OS).\u0000\u0000\u0000CONCLUSION\u0000We utilized peritumoral and intratumoral radiomic features and VDT to generate a model that identify a high-risk group of screen-detected lung cancers associated with poor survival outcomes. These vulnerable subset of screen-detected lung cancers may be candidates for more aggressive surveillance/follow-up and treatment, such as adjuvant therapy.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86951989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Vural, Ayşe Deniz Ertürk Coşkun, G. Çitak, B. Vural, G. Köse
{"title":"The comparison of inflammatory markers in geriatric and nongeriatric endometrial cancers.","authors":"F. Vural, Ayşe Deniz Ertürk Coşkun, G. Çitak, B. Vural, G. Köse","doi":"10.3233/cbm-210215","DOIUrl":"https://doi.org/10.3233/cbm-210215","url":null,"abstract":"BACKGROUND\u0000The inflammatory markers are associated with adverse clinical outcomes in endometrial cancers (EC), but hematopoietic aging may affect the results.\u0000\u0000\u0000OBJECTIVE\u0000To compare inflammatory markers in geriatric and nongeriatric EC.\u0000\u0000\u0000METHODS\u0000This study included 342 women with endometrial cancers (n: 171) and age-matched controls (n: 171). Geriatric (⩾ 65 years old) and nongeriatric women in each group was compared for inflammatory markers, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW).\u0000\u0000\u0000RESULTS\u0000Geriatric EC had more common nonendometrioid tumors, myometrial invasion, lymph node metastasis, advanced stage, and low overall survival (OS). Nongeriatric EC had low MPV, high NLR, and PDW compared to nongeriatric control. Geriatric EC had low MPV, lymphocyte, and high NLR, PLR compared to geriatric control (p< 0.05). Geriatric EC had significantly low PDW and high NLR, PLR compared to nongeriatric EC in early stages, not in advanced stages. Lymphocyte count was significantly low in geriatric EC with all stages (p< 0.05). In nongeriatric EC, stage was related to platelet count (r: 0.341, p: 0.0019), and PLR (r: 0.252, p: 0.01). OS was negatively related to PLR (r: -0.267, p: 0.007) and NLR (r: -0.353, p: 0.000). In geriatric EC, myometrium invasion was negatively related to lymphocyte count (r: -0.268, p: 0.035). OS was related to neutrophil count (p: 0.352, p: 0.01). MPV was negatively related to stage (r: -0.335, p: 0.01) and OS (r: -0.337, p: 0.02).\u0000\u0000\u0000CONCLUSIONS\u0000The inflammatory responses of geriatric and nongeriatric EC were different in the early and advanced stages. Geriatric EC had low PDW and high NLR, PLR compared to nongeriatric EC in early stages. Decreased lymphocyte count was the most prominent feature of geriatric EC in the early and advanced stages. These results suggested that decreased lymphocyte count may reflect an aggressive course of disease in the elderlies. Future inflammation studies may direct anticancer treatment strategies in geriatric EC. Further research on inflammaging and geriatric EC is needed to increase our understanding of aging and carcinogenesis.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82540938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction: FAM196B promotes proliferation and migration via regulating epithelial-mesenchymal transition in esophageal cancer.","authors":"","doi":"10.3233/CBM-229004","DOIUrl":"https://doi.org/10.3233/CBM-229004","url":null,"abstract":"","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81426421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"lncRNA ELFN1-AS1 predicts poor prognosis and promotes tumor progression of non-small cell lung cancer by sponging miR-497.","authors":"Bin Yang, Shuai Miao","doi":"10.3233/cbm-210393","DOIUrl":"https://doi.org/10.3233/cbm-210393","url":null,"abstract":"BACKGROUND\u0000More novel biomarkers need to be discovered to improve the therapeutic efficiency of non-small cell lung cancer (NSCLC). lncRNA ELFN1-AS1 (ELFN1-AS1) was proved to play crucial roles in numerous diseases, its intention in NSCLC remains unclear.\u0000\u0000\u0000OBJECTIVE\u0000This study aimed to investigate the function of ELFN1-AS1 and its potential mechanism in NSCLC development.\u0000\u0000\u0000METHODS\u0000A total of 117 NSCLC patients were recruited and provided paired NSCLC tissues and normal tissues. The expression of ELFN1-AS1 was analyzed by PCR. The biological function of ELFN1-AS1 was estimated by CCK8 and Transwell assay. Additionally, the potential mechanism underlying the function of ELFN1-AS1 was explored by the dual-luciferase reporter assay and western blotting.\u0000\u0000\u0000RESULTS\u0000The significant upregulation of ELFN1-AS1 was found in NSCLC tissues and cells, which was closely associated with the TNM stage, lymph node metastasis status, and overall survival of patients. The knockdown of ELFN1-AS1 was found to inhibit the cellular processes and EMT of NSCLC. Moreover, ELFN1-AS1 was found to serve as a sponge to binding with miR-497, and CCNE1 was demonstrated to be the downstream target of miR-497, which was speculated as the potential mechanism underlying the function of ELFN1-AS1.\u0000\u0000\u0000CONCLUSIONS\u0000ELFN1-AS1 acts as an independent prognostic biomarker and tumor promoter of NSCLC by sponging miR-497/CCNE1 axis.","PeriodicalId":56320,"journal":{"name":"Cancer Biomarkers","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89346573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}