scholarly journals Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 172 ◽  
Author(s):  
Xueli Zhang ◽  
Xiao-Feng Sun ◽  
Bairong Shen ◽  
Hong Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cellular Proliferation ◽  
Pathway Enrichment Analysis ◽  
Protein Biomarkers ◽  
Go Annotation ◽  
Diagnosis And Prognosis ◽  
Ppi Networks ◽  
Potential Applications ◽  
Multiple Biomarkers ◽  
Diagnosis Therapy

In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.

scholarly journals A bioinformatics analysis to identify novel biomarkers for prognosis of pulmonary tuberculosis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yahong Sun ◽  
Gang Chen ◽  
Zhihao Liu ◽  
Lina Yu ◽  
Yan Shang
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bioinformatics Analysis ◽  
Enrichment Analysis ◽  
Gene Clusters ◽  
Pathway Enrichment Analysis ◽  
Go Annotation ◽  
Pathway Enrichment ◽  
Ppi Networks ◽  
Novel Biomarkers ◽  
Geo Database

Abstract Background Due to the fact that pulmonary tuberculosis (PTB) is a highly infectious respiratory disease characterized by high herd susceptibility and hard to be treated, this study aimed to search novel effective biomarkers to improve the prognosis and treatment of PTB patients. Methods Firstly, bioinformatics analysis was performed to identify PTB-related differentially expressed genes (DEGs) from GEO database, which were then subjected to GO annotation and KEGG pathway enrichment analysis to initially describe their functions. Afterwards, clustering analysis was conducted to identify PTB-related gene clusters and relevant PPI networks were established using the STRING database. Results Based on the further differential and clustering analyses, 10 DEGs decreased during PTB development were identified and considered as candidate hub genes. Besides, we retrospectively analyzed some relevant studies and found that 7 genes (CCL20, PTGS2, ICAM1, TIMP1, MMP9, CXCL8 and IL6) presented an intimate correlation with PTB development and had the potential serving as biomarkers. Conclusions Overall, this study provides a theoretical basis for research on novel biomarkers of PTB, and helps to estimate PTB prognosis as well as probe into targeted molecular treatment.

scholarly journals Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the key pathways and central genes of osteosarcoma in vivo

2021 ◽  
Author(s):  
Zhihao Chen ◽  
Xi Wang ◽  
Liubing Li ◽  
Mingxiao Han ◽  
Min Wang ◽  
...  
Keyword(s):  
Protein Modification ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Micro Rna ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Go Annotation ◽  
Pathway Enrichment ◽  
Ppi Networks

Abstract Circular RNAs (circRNAs) play important roles in a variety of pathological functions. However, the potential functions and detailed mechanisms of circRNAs in osteosarcoma (OS) have not been fully elucidated. In this study, the circRNA, micro RNA (miRNA), and messenger RNA (mRNA) expression profile of human OS was investigated based on the raw microarray data GSE140256, GSE65071 and GSE16088 in Gene Expression Omnibus (GEO) datasets, and seven differentially-expressed circRNAs (DEcircRNAs), 166 differentially-expressed miRNAs (DEmiRNAs), and 175 differentially-expressed mRNAs (DEmRNAs) were identified in total. FunRich was employed to analyze the differentially-expressed transcription factors on the basis of identified DEmiRNAs. In addition, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to further study biological functions of the DEmRNAs. Interestingly, post-translational protein modification, collagen-containing extracellular matrix, and single-stranded DNA binding were the most significant pathways enriched for DEmRNAs in GO annotation analysis. Meanwhile, in KEGG pathway enrichment analysis, complement and coagulation cascades, RNA transport and drug metabolism − other enzymes were the most significantly enriched pathways of DEmRNAs in OS. We constructed circRNA-miRNA-mRNA and protein–protein interaction (PPI) networks that may be associated with pathological processes of OS. Finally, we also revealed the pattern of tumor-infiltrating immune cells in OS and further explored the ceRNA networks we constructed in which we found that COL1A1 and RAN were significantly correlated with overall survival in patients with osteosarcoma (p < 0.05). To our knowledge, this study provides the first profile analysis of DEcircRNAs, DEmiRNAs, and DEmRNAs with OS in vivo and reveals a novel idea for understanding the pathogenesis of OS.

scholarly journals Epigenetic Biomarkers: Potential Applications in Gastrointestinal Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jiaqiu Li ◽  
Hongchuan Jin ◽  
Xian Wang
Keyword(s):  
Colorectal Cancer ◽  
Chromatin Remodeling ◽  
Noncoding Rnas ◽  
Clinical Applications ◽  
Epigenetic Mechanisms ◽  
Gastrointestinal Cancers ◽  
Diagnosis And Prognosis ◽  
Epigenetic Biomarkers ◽  
Cancer Initiation ◽  
Potential Applications

Genetics and epigenetics coregulate the cancer initiation and progression. Epigenetic mechanisms include DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs. Aberrant epigenetic modifications play a fundamental role in the formation of gastrointestinal cancers. Advances in epigenetics offer a better understanding of the carcinogenesis and provide new insights into the discovery of biomarkers for diagnosis, and prognosis prediction of human cancers. This review aims to overview the epigenetic aberrance and the clinical applications as biomarkers in gastrointestinal cancers mainly gastric cancer and colorectal cancer.

scholarly journals Network Pharmacology Validation of Therapeutic Mechanisms of Tanshinone IIA in Colorectal Cancer

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110042
Author(s):  
Zhiyuan Sun ◽  
Jinxiang Dong ◽  
Lijie Song ◽  
Fuqiang Li ◽  
Xue Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tanshinone Iia ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Networks ◽  
Therapeutic Mechanisms ◽  
Cell Cycling ◽  
Promising Source

Curative therapies with fewer adverse effects are required for cancer treatment. Medicinal plants represent a promising source of novel therapeutic candidates. We employed network pharmacology to predict potential molecular mechanisms of salvia root-derived tanshinone IIA (Tan IIA) in the treatment of colorectal cancer (CRC), followed by empirical validation. The Traditional Chinese Medicine System Pharmacology (TCMSP), DrugBank, and GeneCards databases were queried to identify overlapping Tan IIA (therapeutic)- and CRC (disease)-relevant protein targets. Cytoscape and STRING were used to generate component-target and protein-protein interaction (PPI) networks, respectively, and topology analysis identified highly connected nodes within the latter. Target proteins were subjected to gene ontology (GO)-based biological process annotation using DAVID, and to biological pathway enrichment analysis using the Kyoto encyclopedia and genome (KEGG) database. Enriched biological processes included cell cycling and proliferation, and enriched KEGG pathways included neuroactive ligand-receptor interaction, PI3K-Akt, and cancer. Network pharmacology results predicted that Tan IIA impacts multiple targets and pathways, but that its therapeutic effect is predominantly attributable to cell cycle regulation, inhibition of cell proliferation, and induction of apoptosis. Investigation of the in vitro impact of Tan IIA on proliferation, viability, and cell cycling of 2 hoursuman CRC cell lines (SW480 and SW620), using the CCK-8 method and flow cytometry, demonstrated that Tan IIA significantly inhibits cell proliferation via inducing cell cycle arrest in the G2/M phase. Network pharmacology-predicted hypotheses were thus empirically validated, providing a basis for in-depth study of the therapeutic mechanisms of Tan IIA in the context of CRC.

scholarly journals A Network-Based Methodology to Identify Subnetwork Markers for Diagnosis and Prognosis of Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Olfat Al-Harazi ◽  
Ibrahim H. Kaya ◽  
Achraf El Allali ◽  
Dilek Colak
Keyword(s):  
Colorectal Cancer ◽  
Disease Diagnosis ◽  
Disease Classification ◽  
Support Vector ◽  
Svm Classifier ◽  
Gene Interaction Network ◽  
Individual Gene ◽  
Network Analyses ◽  
Diagnosis And Prognosis ◽  
Ppi Networks

The development of reliable methods for identification of robust biomarkers for complex diseases is critical for disease diagnosis and prognosis efforts. Integrating multi-omics data with protein-protein interaction (PPI) networks to investigate diseases may help better understand disease characteristics at the molecular level. In this study, we developed and tested a novel network-based method to detect subnetwork markers for patients with colorectal cancer (CRC). We performed an integrated omics analysis using whole-genome gene expression profiling and copy number alterations (CNAs) datasets followed by building a gene interaction network for the significantly altered genes. We then clustered the constructed gene network into subnetworks and assigned a score for each significant subnetwork. We developed a support vector machine (SVM) classifier using these scores as feature values and tested the methodology in independent CRC transcriptomic datasets. The network analysis resulted in 15 subnetwork markers that revealed several hub genes that may play a significant role in colorectal cancer, including PTP4A3, FGFR2, PTX3, AURKA, FEN1, INHBA, and YES1. The 15-subnetwork classifier displayed over 98 percent accuracy in detecting patients with CRC. In comparison to individual gene biomarkers, subnetwork markers based on integrated multi-omics and network analyses may lead to better disease classification, diagnosis, and prognosis.

scholarly journals Circulating Biomarkers of Colorectal Cancer (CRC)—Their Utility in Diagnosis and Prognosis

2021 ◽  
Vol 10 (11) ◽  
pp. 2391
Author(s):  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Mediators ◽  
Colorectal Adenomas ◽  
Global Burden ◽  
Circulating Biomarkers ◽  
Specific Nature ◽  
Diagnosis And Prognosis ◽  
Specific Proteins ◽  
Novel Biomarkers ◽  
Number Of Publications

The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.

scholarly journals Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2723
Author(s):  
Yu-Ping Yang ◽  
Teresa M. Giret ◽  
Richard J. Cote
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Detection Sensitivity ◽  
Clinical Utilization ◽  
Diagnosis And Prognosis ◽  
Early Cancer Diagnosis ◽  
Potential Marker ◽  
Potential Applications ◽  
Downstream Analysis

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.

scholarly journals The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jinhui Hu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Nuclear Export ◽  
Messenger Rna ◽  
Regulatory Proteins ◽  
Biological Processes ◽  
The Past ◽  
Common Cancer ◽  
Potential Applications ◽  
Regulated Gene Expression

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

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