scholarly journals Novel Methylation Biomarkers for Colorectal Cancer Prognosis

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1722
Author(s):  
Alvaro Gutierrez ◽  
Hannah Demond ◽  
Priscilla Brebi ◽  
Carmen Gloria Ili
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Progression ◽  
Mapk Pathway ◽  
Cancer Prognosis ◽  
Epigenetic Changes ◽  
Metastasis Formation ◽  
Common Cancer ◽  
Cycle Regulation ◽  
Multiple Signaling

Colorectal cancer (CRC) comprises the third most common cancer worldwide and the second regarding number of deaths. In order to make a correct and early diagnosis to predict metastasis formation, biomarkers are an important tool. Although there are multiple signaling pathways associated with cancer progression, the most recognized are the MAPK pathway, p53 pathway, and TGF-β pathway. These pathways regulate many important functions in the cell, such as cell cycle regulation, proliferation, differentiation, and metastasis formation, among others. Changes in expression in genes belonging to these pathways are drivers of carcinogenesis. Often these expression changes are caused by mutations; however, epigenetic changes, such as DNA methylation, are increasingly acknowledged to play a role in the deregulation of oncogenic genes. This makes DNA methylation changes an interesting biomarkers in cancer. Among the newly identified biomarkers for CRC metastasis INHBB, SMOC2, BDNF, and TBRG4 are included, all of which are highly deregulated by methylation and closely associated with metastasis. The identification of such biomarkers in metastasis of CRC may allow a better treatment and early identification of cancer formation in order to perform better diagnostics and improve the life expectancy.

Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Target Prediction ◽  
Computational Prediction ◽  
Initial Step ◽  
Kegg Pathways ◽  
Candidate Mirnas ◽  
Common Cancer ◽  
Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

scholarly journals Transketolase-Like 1 Expression Is Modulated during Colorectal Cancer Progression and Metastasis Formation

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e25323 ◽  
Author(s):  
Santiago Diaz-Moralli ◽  
Miriam Tarrado-Castellarnau ◽  
Cristina Alenda ◽  
Antoni Castells ◽  
Marta Cascante
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Metastasis Formation ◽  
Colorectal Cancer Progression

scholarly journals MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tong Niu ◽  
Weiwei Zhang ◽  
Wei Xiao
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Small Population ◽  
Biological Processes ◽  
Microrna Regulation ◽  
Common Cancer ◽  
Multiple Characteristics ◽  
Multiple Signaling

AbstractBreast cancer is the most common cancer among women and accounts for 30% of all female malignancies worldwide. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that exhibit multiple characteristics including differentiation capacity, self-renewal and therapeutic resistance. Recently, BCSCs have attracted attention due to their modulation of breast tumor behaviors and drug resistance. miRNAs are small noncoding mRNAs involved in virtually all biological processes, including stem cell development, maintenance and differentiation. In breast cancer, miRNAs appear to be multi-faceted since they can act as either suppressors or oncogenes to regulate breast cancer progression. This review summarizes the critical roles of miRNAs in regulating multiple signaling pathways such as Wnt/β-catenin, Notch, PI3K/AKT/mTOR, BMI-1 and STAT3 that are important for the BCSC maintenance.

scholarly journals Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery

2017 ◽  
Author(s):  
Yue Hu ◽  
Jochen Gaedcke ◽  
Georg Emons ◽  
Tim Beissbarth ◽  
Marian Grade ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Susceptibility ◽  
Disease Free Survival ◽  
Colorectal Cancer Risk ◽  
Cancer Prognosis ◽  
Disease Free

AbstractBackgroundColorectal cancer (CRC) is among the leading causes of cancer death. Rectal cancers account for one third of CRC cases. The role and significance of colorectal cancer risk loci in rectal cancer progression has not been investigated.MethodsWe generated and explored a dataset from 230 rectal cancer patients by gene expression microarray analysis of cancer samples and matched controls, and SNP arrays of germline DNA.Results8q24 (upstream of MYC) and 18q21 (in the intron of SMAD7), two of the loci most strongly linked with colorectal cancer risk, as well as 20q13 (in the intron of LAMA5), are tightly associated with the prognosis of rectal cancer patients. For SNPs on 18q21 (rs12953717 and rs4464148) and 20q13 (rs4925386), alleles that correlate with higher risk for the development of colorectal cancer are associated with shorter disease free survival. However, for rs6983267 on 8q24, the low risk allele is associated with a higher risk for recurrence and metastasis after surgery, and importantly, is strongly correlated with the resistance of colorectal cancer cell lines to chemoradiotherapy. We also found that although MYC expression is dramatically increased in cancer, patients with higher levels of MYC have a better prognosis. The expression of SMAD7 is weakly correlated with disease free time. Notably, the presence of the 8q24 and 18q21 SNP alleles is not correlated with a change of expression of MYC and SMAD7. rs4464148, and probably rs6983267 and rs4925386, are linked with overall survival time of patients.ConclusionsSNPs at three colorectal cancer risk loci detect subpopulations of rectal cancer patients with poor prognosis. rs6983267 probably affects prognosis through interfering with the resistance of cancer cells to chemoradiotherapy.

scholarly journals Biomarker alterations associated with distinct patterns of metastatic spread in colorectal cancer

2020 ◽  
Author(s):  
M. Michl ◽  
F. Taverna ◽  
J. Kumbrink ◽  
T. S. Schiergens ◽  
V. Heinemann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Lung Metastasis ◽  
Mapk Pathway ◽  
Expression Profiles ◽  
Metastatic Spread ◽  
Control Group ◽  
Metastasis Formation ◽  
Metastatic Patterns ◽  
Distant Spread

AbstractMetastatic spread is the most important life-threatening feature of colorectal cancer and is supposed to be mainly driven by alterations in different carcinogenic pathways. The present study compared mutation and expression profiles of distinctive biomarkers in colorectal cancer patients with different clinical metastatic patterns. As for a case-control study, patients were matched according to T category, grading and primary tumour site. Overall, 246 patients with either exclusive lung metastasis (N = 82), exclusive liver metastasis (N = 82) or non-metastatic colorectal cancer (N = 82) were identified. Paraffin-embedded specimens were examined for mutations in the RAS and RAF genes and for the expression of β-catenin and CD133. Clinical endpoints were presence or absence of distant metastasis, formation of metastasis in lungs versus the liver and survival. MAPK pathway mutations in either the KRAS, NRAS or BRAF gene were associated with the development of lung metastasis (63.4%) compared to the control group (47.6%; p = 0.04). MAPK pathway alterations plus high β-catenin expression were associated with metastasis to the lungs but not to the liver (28.0% vs. 13.4%; p = 0.02). High CD133 expression correlated with the development of liver metastasis compared to the control group (30.5% vs. 14.6%; p = 0.02). This data indicates that different patterns of distant spread are associated with specific biomarker alterations and may represent different molecular subtypes of colorectal cancer. However, underlying mechanisms of metastasis formation in different anatomic sites remains unclear. Since knowledge of the anticipated site of distant spread would substantially impact clinical management, further research is needed to identify solid biomarkers for different metastatic patterns.

scholarly journals Editing and Expression of miR-589-5p as an Important Biomarker in Colorectal Cancer

2020 ◽  
Author(s):  
Yuanyi Yue ◽  
Qiang Zhang ◽  
Li Xiao
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Expression Levels ◽  
The Third ◽  
Common Cancer ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Mirna Editing ◽  
Editing Level

Abstract Objectives: Colorectal cancer (CRC) is recognized as the third most common cancer worldwide. Recently, emerging evidence showed that microRNA (miRNA) A-to-I editing plays crucial roles in cancer prognosis as well as cancer therapy. However, the relationship between CRC and miRNA editing remains not fully understood. Herein, we presented the first comprehensive analysis of miRNA editing events in CRC. Methods: Using patient data from The Cancer Genome Atlas (TCGA), we performed editing events and detected the expression levels of miR-589-5p. Results: we identified both editing events and the expression levels of miR-589-5p are significantly associated with Consensus Molecular Subtyping (CMS), especially for CMS4. The editing and expression levels of miR-589-5p impact almost completely different sets of gene expression, indicating the edited miR-589-5p plays a different role in CRC progression, compared to the wildtype miR-589-5p. Conclusions: In conclusion, our study provided the first association of miRNA editing and CRC. We demonstrated that expression and editing level of miR‑589‑5p may work as a novel biomarker for both prognosis and diagnosis in CRC.

scholarly journals Regulation Network of Colorectal Cancer Specific Enhancers in Progression of Colorectal Cancer

2021 ◽  
Author(s):  
Bohan Chen ◽  
Yiping Ma ◽  
Jinfang Bi ◽  
Wenbin Wang ◽  
Anshun He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chromatin Structure ◽  
Therapeutic Targets ◽  
Higher Order ◽  
Epigenetic Changes ◽  
Rna Seq ◽  
Normal Cells ◽  
Regulation Network

Enhancers regulate multiple genes through higher-order chromatin structure and further affect cancer progression. Epigenetic changes in cancer cells activate several cancer specific enhancers that are silenced in normal cells. These cancer specific enhancers are potential therapeutic targets of cancer. However, functions and regulation network of colorectal cancer specific enhancers are still unknown. Here in this study, we profile colorectal cancer specific enhancers and reveal the regulation network of these enhancers by analysis of HiChIP, Hi-C and RNA-seq data. We propose the regulation network of colorectal cancer specific enhancers plays important role in progression of colorectal cancer.

scholarly journals Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2710
Author(s):  
Carmen Ili ◽  
Kurt Buchegger ◽  
Hannah Demond ◽  
Juan Castillo-Fernandez ◽  
Gavin Kelsey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Cpg Island ◽  
The Cancer Genome Atlas ◽  
Node Metastasis ◽  
Genome Wide

Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, FIGN, HTRA3, BDNF, HCN4 and STAC2 genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.

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