scholarly journals Computational Analysis of Specific MicroRNA Biomarkers for Noninvasive Early Cancer Detection

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tianci Song ◽  
Yanchun Liang ◽  
Zhongbo Cao ◽  
Wei Du ◽  
Ying Li
Keyword(s):  
Early Detection ◽  
Cancer Detection ◽  
Target Gene ◽  
Complex Disease ◽  
Early Stage ◽  
Function Analysis ◽  
Expression Patterns ◽  
Potential Candidate ◽  
Cancer Types ◽  
And Function

Cancer is a complex disease residing in various tissues of human body, accompanied with many abnormalities and mutations in genomes, transcriptome, and epigenome. Early detection plays a crucial role in extending survival time of all major cancer types. Recent advances in microarray and sequencing techniques have given more support to identifying effective biomarkers for early detection of cancer. MicroRNAs (miRNAs) are more and more frequently used as candidates for biomarkers in cancer related studies due to their regulation of target gene expression. In this paper, the comparative analysis is used to discover miRNA expression patterns in cancer versus normal samples on early stage of eight prevalent cancer types. Our work focuses on the specific miRNAs biomarkers identification and function analysis. Several identified miRNA biomarkers in this paper are matched well with those reported in existing researches, and most of them could serve as potential candidate indicators for clinical early diagnosis applications.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

An ultrasensitive method for noninvasive pan-cancer early detection based on targeted methylation sequencing of cell-free DNA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10544-10544
Author(s):  
Tiancheng Han ◽  
Yuanyuan Hong ◽  
Pei Zhihua ◽  
Song Xiaofeng ◽  
Jianing Yu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Detection ◽  
Real World ◽  
Early Stage ◽  
Validation Dataset ◽  
Cpg Sites ◽  
Free Dna ◽  
Cancer Types ◽  
Discovery Dataset ◽  
Pan Cancer

10544 Background: Screening the biomarkers from the cell-free DNA (cfDNA) of peripheral blood is a non-invasive and promising method for cancer diagnosis. Among diverse types of biomarkers, epigenetic biomarkers have been reported to be one of the most promising ones. Epigenetic modifications are widespread on the human genome and generally have strong signals due to the similar methylation patterns shared by adjacent CpG sites. Although some epigenetic diagnostic methods have been developed based on cfDNAs, few of them could be applied to pan-cancer and their sensitivities are barely satisfactory for early cancer detection. Methods: Targeted methylation sequencing was performed using our in-house-designed panel targeting regions with abundant cancer-specific methylation CpGs. The cfDNA samples from 80 healthy individuals and 549 cancer patients of 14 cancer types were separately sequenced. The dataset was randomly split into one discovery dataset and one validation dataset. Moreover, cfDNA samples from four cancer patients were diluted with the healthy cfDNAs to generate 12 in vitro simulated samples with low circulating tumor DNA (ctDNA) fraction. Additionally, DNAs extracted from 130 unmatched tumor formalin fixation and paraffin embedding (FFPE) samples of 10 cancer types were sequenced to screen the diagnostic biomarkers. Adjacent CpG sites were first merged into methylation-correlated blocks (MCB) according to their correlations of methylation levels in tumor DNAs. The MCBs with higher methylation levels in tumor DNAs than that of healthy cfDNAs (from the discovery dataset) were defined as our hypermethylation biomarkers. For each cfDNA sample, a hypermethylation score (HM-score) was computed to measure the overall methylation level difference of selected biomarkers. The performance of our method was evaluated with the real-world dataset, while the limit of detection was estimated using the simulated low-ctDNA samples. Results: Our model based on 37 hypermethylation MCB biomarkers achieved an area under the curve (AUC) of 0.89 and 0.86 in the real-world pan-cancer discovery and validation cfDNA datasets, respectively. Furthermore, the overall specificity and sensitivity are 100% and 76.19% in the discovery dataset, and 96.67% and 72.86% in the validation dataset. In the validation dataset, 28/40 (70%) of early-stage colorectal cancer patients and 10/20 (50%) of non-small-cell lung cancer patients were successfully diagnosed. Additionally, all the simulated samples with theoretical ctDNA factions over 0.5% were predicted as diseased, demonstrating the ability of our method to detect tumor signals at early stages. Conclusions: Our cfDNA-based epigenetic method outperforms currently available methods in various cancer types, and is promising to be applied to early-stage cancer detection and samples with low ctDNA fractions.

scholarly journals Genome-wide identification of ZF-HD gene family in Triticum aestivum: Molecular evolution mechanism and function analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256579
Author(s):  
Hongli Niu ◽  
Pengliang Xia ◽  
Yifeng Hu ◽  
Chuang Zhan ◽  
Yiting Li ◽  
...  
Keyword(s):  
Gene Family ◽  
Function Analysis ◽  
Expression Patterns ◽  
Pcr Analysis ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Wheat Evolution ◽  
New Perspective ◽  
Almost All ◽  
And Function

ZF-HD family genes play important roles in plant growth and development. Studies about the whole genome analysis of ZF-HD gene family have been reported in some plant species. In this study, the whole genome identification and expression profile of the ZF-HD gene family were analyzed for the first time in wheat. A total of 37 TaZF-HD genes were identified and divided into TaMIF and TaZHD subfamilies according to the conserved domain. The phylogeny tree of the TaZF-HD proteins was further divided into six groups based on the phylogenetic relationship. The 37 TaZF-HDs were distributed on 18 of 21 chromosomes, and almost all the genes had no introns. Gene duplication and Ka/Ks analysis showed that the gene family may have experienced powerful purification selection pressure during wheat evolution. The qRT-PCR analysis showed that TaZF-HD genes had significant expression patterns in different biotic stress and abiotic stress. Through subcellular localization experiments, we found that TaZHD6-3B was located in the nucleus, while TaMIF4-5D was located in the cell membrane and nucleus. Our research contributes to a comprehensive understanding of the TaZF-HD family, provides a new perspective for further research on the biological functions of TaZF-HD genes in wheat.

scholarly journals Early Detection is as Important as Imatinib in CML Treatment Success

2019 ◽  
Author(s):  
Dmitriy Sonkin ◽  
Richard Simon
Keyword(s):  
Early Detection ◽  
Cancer Detection ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Systemic Treatment ◽  
Early Cancer ◽  
Early Stage ◽  
Treatment Success ◽  
Myelogenous Leukemia ◽  
Clinical Benefits

Chronic myelogenous leukemia (CML) was the first malignancy for which clinical outcome was drastically improved by kinase inhibitor therapy. Kinase inhibitors targeting other well-known oncogenes have been introduced into clinical practice, but none have shown the same magnitude of clinical benefit as ABL1 inhibition in CML. We argue that early detection is an underappreciated, but critically important factor in success of ABL1 inhibitors in treatment of CML. We show that CML provides a window into how many types of cancer may look and behave at an early stage, prior to diagnosis and the development of additional genomic alterations. The remarkable clinical benefits of ABL1 inhibition is likely due to early detection of CML at a stage in which the tumor is driven by single oncogenic alteration which can be successfully controlled by the inhibitor. Thinking of CML as a prototype for effective systemic treatment based on early cancer detection may help to develop strategies for improving treatment for other types of cancer.

scholarly journals Genome-wide analysis of lncRNAs and mRNAs expression during the differentiation of abdominal preadipocytes in chicken

2016 ◽  
Author(s):  
Tao Zhang ◽  
Xiangqian Zhang ◽  
Kunpeng Han ◽  
Genxi Zhang ◽  
Jinyu Wang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Rna Sequencing ◽  
Early Stage ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Valuable Resource ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
And Function ◽  
Jinghai Yellow Chicken

AbstractlncRNAs regulate metabolic tissue development and function, including adipogenesis. However, little is known about the function and profile of lncRNAs in preadipocytes differentiation of chicken. Here, we identified lncRNAs in preadipocytes of different differentiation stages by RNA-sequencing using Jinghai Yellow chicken. A total of 1,300,074,528 clean reads and 27,023 lncRNAs were obtained from twenty samples. 3095 genes (1,336 lncRNAs and 1,759 mRNAs) were differentially expressed among different stages, of which the number of DEGs decreased with the differentiation, demonstrating that the early stage might be most important for chicken preadipocytes differentiation. Furthermore, 3,095 DEGs were clustered into 8 clusters with their expression patterns by K-means clustering. We identified six stage-specific modules related to A0, A2 and A6 stages using weighted co-expression network analysis. Many well-known/novel pathways associated with preadipocytes differentiation were found. We also identified highly connected genes in each module and visualized them by cytoscape. Many well-known genes related to preadipocytes differentiation were found such as IGFBP2 and JUN. Yet, the majority of high connected genes were unknown in chicken preadipocytes. This study provides a valuable resource for chicken lncRNA study and contributes to batter understanding the biology of preadipocytes differentiation in chicken.

Genome-wide cell-free DNA (cfDNA) methylation signatures and effect on tissue of origin (TOO) performance.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3049-3049 ◽  
Author(s):  
Minetta C. Liu ◽  
Arash Jamshidi ◽  
Oliver Venn ◽  
Alexander P. Fields ◽  
M. Cyrus Maher ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Multiple Cancer ◽  
Isolated Cells ◽  
Genome Wide ◽  
Ffpe Tumor ◽  
Formalin Fixed Paraffin Embedded ◽  
Cancer Types

3049 Background: For multi-cancer detection using cfDNA, TOO determination is critical to enable safe and efficient diagnostic follow-up. Previous array-based studies captured < 2% of genomic CpGs. Here, we report genome-wide fragment-level methylation patterns across 811 cancer cell methylomes representing 21 tumor types (97% of SEER cancer incidence), and define effects of this methylation database on TOO prediction within a machine learning framework. Methods: Genomic DNA from 655 formalin-fixed paraffin-embedded (FFPE) tumor tissues and 156 isolated cells from tumors was subjected to a prototype 30x whole-genome bisulfite sequencing (WGBS) assay, as previously reported in the Circulating Cell-free Genome Atlas (CCGA) study (NCT02889978). Two independent TOO models, one with and one without the methylation database, were fitted on training samples; each was used to predict on the test set. A WGBS classifier was used to detect cancer at 98% specificity; reported TOO results reflect percent agreement between predicted and true TOO among those detected cancers (166 cases: 81 stage I-III, 69 stage IV, 16 non-informative). Results: Genome-wide methylation data generated from this database allowed fragment-level analysis and coverage of ~30 million CpGs across the genome (~60-fold greater than array-based approaches). Incorrect TOO assignments decreased by 35% (20% to 13%) after incorporating methylation database information into TOO classification. Improvement was observed across all cancer types and was consistent in early-stage cancers (stage I-III). Respective performances in breast cancer (n = 23) were 87% vs 96%; in lung cancer (n = 32) were 85% vs 88%; in hepatobiliary (n = 10) were 70% vs 90%; and in pancreatic cancer (n = 17) were 94% vs 100%. Results using an optimized approach informed by these results in a large cohort of CCGA participants will be reported. Conclusions: Incorporating data from a large methylation database improved TOO performance in multiple cancer types. This supports feasibility of this methylation-based approach as an early cancer detection test across cancer types. Clinical trial information: NCT02889978.

A novel biophysical based marker with multilevel, multiparameter expression for early stage cancer detection.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20673-e20673
Author(s):  
Junjie Wu ◽  
Gengxi Jiang ◽  
Jiansong Ji ◽  
Xuedong Du ◽  
Yue Lin ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Cancer Detection ◽  
Early Stage ◽  
Physical Property ◽  
Stage I ◽  
Potential Candidate ◽  
Healthy Individuals ◽  
Blind Test ◽  
Early Stage Cancer ◽  
Multi Level

e20673 Background: Early stage cancer detection remains to be elusive despite of many years of efforts. In this work, a bio-physical based marker (named Cancer Differentiation Analysis (CDA)) with multi-level and multi-parameter expression features has been developed which has shown a number of clear advantages over the traditional approaches such as bio-chemistry based marker, circulating tumor cell (CTC) and circuiting DNA (ct-DNA). In stage I non-small cell lung cancer (NSCLC), sensitivity and specificity reached a record high of 85.2% and 93.0%, respectively. Methods: In this study, 832 NSCLC cancer samples with pathological information and 642 samples from healthy individuals were measured in a single blind test. Peripheral blood of each individual was drawn in EDTA tubes. One class of bio-physical property in blood samples was utilized for CDA tests. The CDA data were first processed using an algorithm built from data base and subsequently analyzed using SPSS. The results were shown in the table. Results: The results indicated that CDA technology has a very good sensitivity and specificity even at stage I (85% and 93%, respectively), which is much better than those previously reported results by other methods. Conclusions: Initial results showed that CDA technology could effectively screen NSCLC patients from healthy individuals. As a novel bio-physical based cancer detection approach with multi-level and multi-parameter expressions, CDA technology could be a potential candidate for early stage cancer screening. [Table: see text]

scholarly journals Immature symbiotic system between horizontally transmitted green algae and brown hydra

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Miyokawa ◽  
Hiroyuki J. Kanaya ◽  
Taichi Q. Itoh ◽  
Yoshitaka Kobayakawa ◽  
Junko Kusumi
Keyword(s):  
Green Algae ◽  
Lysosomal Enzymes ◽  
Early Stage ◽  
Expression Patterns ◽  
Symbiotic System ◽  
Hydra Vulgaris ◽  
In The Wild ◽  
And Function ◽  
The Relationship ◽  
Gene Expression Levels

AbstractSome strains of brown hydra (Hydra vulgaris) are able to harbor the green algae Chlorococcum in their endodermal epithelial cells as symbionts. However, the relationship between brown hydra and chlorococcum is considered to be incipient symbiosis because most artificially introduced symbionts are not stable and because symbiotic H. vulgaris strains are rare in the wild. In this study, we compared the gene expression levels of the newly established symbiotic hydra (strain 105G), the native symbiotic strain (J7), and their non-symbiotic polyps to determine what changes would occur at the early stage of the evolution of symbiosis. We found that both the 105G and J7 strains showed comparable expression patterns, exhibiting upregulation of lysosomal enzymes and downregulation of genes related to nematocyte development and function. Meanwhile, genes involved in translation and the respiratory chain were upregulated only in strain 105G. Furthermore, treatment with rapamycin, which inhibits translation activity, induced the degeneration of the symbiotic strains (105G and J7). This effect was severe in strain 105G. Our results suggested that evolving the ability to balance the cellular metabolism between the host and the symbiont is a key requirement for adapting to endosymbiosis with chlorococcum.

Discovery of a core-panel of markers for a blood-assay for cancer detection utilizing cfDNA methylation changes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1522-1522
Author(s):  
Lasika Seneviratne ◽  
Steven Evans ◽  
Juvairiya Pulicharam ◽  
Nadir Arber ◽  
Jacob Kuint
Keyword(s):  
Cancer Screening ◽  
Cancer Detection ◽  
Screening Test ◽  
Early Stage ◽  
Smoking History ◽  
Training Set ◽  
Blood Draw ◽  
Multicenter Observational Study ◽  
Specificity And Sensitivity ◽  
Cancer Types

1522 Background: Cancer screening is limited to several cancers despite improved outcome A screening test should be acceptable, safe, and relatively inexpensive1 Tumors shed cfDNA to the blood where abundant tumor-specific methylation changes can be detected 1https://www.who.int/cancer/detection/variouscancer/en/. Methods: This is a prospective, multicenter, observational study under two protocols NCT04264767, NCT04264754. Plasma was collected from 1,255 subjects: 586 treatment-naïve cancer patients and 639 controls, in 21 sites and biobanks. Training set I (211 cases/99 controls) was used to select the 6 final markers for the core panel, training set II (200 controls) was used to lock the algorithm, and set the threshold to a score yielding specificity of 95%. The validation set (342 cases/310 controls) was performed utilizing the pre-specified algorithm and threshold. Plasma was separated from a single EDTA tube within 4 hours of blood draw. EpiCheck’s reagents and methylation-sensitive enzymes (Nucleix, Israel) were used for DNA extraction, digestion, and amplification in real-time PCR (ABI 7500 Fast Dx, Applied Biosystems). Results: Age was comparable but sex and smoking history were different (more women in cases, more smokers in controls). In the validation cohort twelve cancer types were included, with prominent representation of major cancer types (19% Breast, 14% colorectal and 21% lung) and stages I&II (56%). Specificity and sensitivity were maintained high at 94% and 62%. Highest sensitivity was demonstrated in GI cancers (77% colorectal, 83% esophageal, 100% gastric) and non-solid malignancies (83%). Sensitivity in early stage cancers (stages I, II & IIIA) was 71%, led by Sarcoma (83%) esophageal (76%) and colorectal (61%). Conclusions: This 6-marker blood-based methylation assay is a promising initial component in a future cancer screening test, generating significant signal in early cancers and utilizing simple and inexpensive PCR technology. Clinical trial information: NCT04264767, NCT04264754. [Table: see text]

scholarly journals Prostate Biopsy Strategies: Current State of the Art

2004 ◽  
Vol 2 (3) ◽  
pp. 213-222
Author(s):  
Badar M. Mian
Keyword(s):  
Early Detection ◽  
Cancer Detection ◽  
Prostate Biopsy ◽  
Early Stage ◽  
Specific Antigen ◽  
Transrectal Ultrasound ◽  
Intraepithelial Neoplasia ◽  
Peripheral Zone ◽  
Detection Rates ◽  
Psa Testing

Prostate-specific antigen testing and prostate biopsy have revolutionized our ability to detect prostate cancer at an early stage. The transrectal ultrasound-guided biopsy procedure has undergone a number of modifications over the past 10 years to meet our goal of early detection of cancer at a curable stage. Biopsy schemes have evolved from lesion-directed biopsies to systematic mapping of the peripheral zone of the prostate, which harbors almost all of the significant tumor foci. An increase in the number of biopsy cores from 6 to 10 (or 12) has resulted in a significant improvement in the detection of clinically localized cancer, without any appreciable increase in the number of indolent cancers. Current biopsy schemes also have enhanced our ability to determine the true prognostic value of pathologic lesions such as high-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation which have been associated with cancer detection in repeat biopsies. I discuss the rationale behind, and the outcomes of, various biopsy strategies. More than 15 years after PSA testing was popularized for early detection, a number of men are presenting for evaluation regarding repeat prostate biopsy for various clinical indications. The indications, biopsy scheme, and cancer detection rates for repeat prostate biopsy are discussed in detail.

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