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

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.

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Combined Analysis of the Aberrant Epigenetic Alteration of Colorectal Cancer

10.21203/rs.3.rs-37093/v1 ◽

2020 ◽

Author(s):

Xiao-liang Xing ◽

Zhi-Yong Yao ◽

Ti Zhang ◽

Ning Zhu ◽

Xingyu Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Adenocarcinoma ◽

Differential Methylation ◽

The Cancer Genome Atlas ◽

The Third ◽

Common Cancer ◽

Differential Expression Genes ◽

Cancer Genome Atlas ◽

Genome Atlas ◽

Potential Biomarkers

Abstract BackgroundColorectal cancer (CRC) is the third most common cancer which could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) mainly. Accumulating evidence indicatedmethylations are involved in multiple tumors.MethodsTo know the effect of abnormal methylation in COAD, READ and CRC, we downloaded methylation and mRNA data of COAD and READ from The Cancer Genome Atlas (TCGA) database. And then, we used DESeq2, ChAMP, DAVID 6.8, Cytoscape_3.7.2 and Correlation analysis to identify the potential biomarkers.ResultsWe obtain 12 potential biomarkers (APBB1, CDC42SE2, EIF4E3, FBXO17, FES, GNPNAT1, HSPA1A, OSBPL3, RORC, SALL1, SPEG, and TCF7L1) directly associated with the pathologic TNM of COAD maybe regulated by 28 differential methylations; 2 potential biomarkers (AQP1 and HOXA3) directly associated with pathologic NM maybe regulated by 8 differential methylations; and 15 potential biomarkers (ADAMTSL3, ANXA9, APBB1, AQP1, C2CD4A, CLIP3, DNAJC15, EIF4E3, FAM160A1, GNG4, HLX, HSPA1A, LAYN, NR3C2, and SYT1)directly associated with the pathologic TNM of COAD maybe regulated by 29 differential methylations. Furthermore, weconstruct the network of differential methylation and differential expression genes. In addition, we also obtain 1 methylation (cg18149207), 2 methylations (cg02000808 and cg21134232) and 2 methylations (cg04408595 and cg19413725) associated with the overall survival.ConclusionOur results provide an analysis of theoretical knowledge and clinical outcomes, but more researches are needed to confirm our findings.

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Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

Future Oncology ◽

10.2217/fon-2020-1163 ◽

2021 ◽

Author(s):

Xiao-Cheng Wang ◽

Ya Liu ◽

Fei-Wu Long ◽

Liang-Ren Liu ◽

Chuan-Wen Fan

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Markers ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Free Survival ◽

Cancer Genome Atlas ◽

Bioinformatic Approaches ◽

Cell Phenotypes ◽

The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

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CPXM1: a novel biomarker for gastric cancer prognosis

10.21203/rs.3.rs-337128/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Mengxiang Zhu ◽

Wenwu Yan ◽

Changsheng Yao ◽

Qingyi Li ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Signal Pathways ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

Abstract Background The molecular role of carboxypeptidase X, M14 family member (CPXM1) in oncogenesis or tumor progression remains unclear. The aim of this study was to determine whether CPXM1 can be used as a potential prognostic biomarker for gastric cancer (GC). Methods We first demonstrated the relationship between CPXM1 expression and GC in various public databases. Secondly, the expression of CPXM1 in GC tissues was further verified by immunohistochemical staining using tissue microarray containing 96 cases of GC patients. Kaplan–Meier analysis and a Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CPXM1 and the survival of GC patients. Finally, we used the expression data of CPXM1 in The Cancer Genome Atlas database to predict CPXM1-related signaling pathways through bioinformatics analysis. Results The expression level of CPXM1 in GC tissues was significantly correlated with tumor size (p = 0.041) and lymph node metastasis (p = 0.014). In addition, Kaplan–Meier analysis showed that the expression of CPXM1 in GC tissues was significantly associated with poor prognosis (p = 0.011). Multivariate analysis indicated that CPXM1 is a potential predictor of poor prognosis in GC patients (p = 0.026). The results of biosynthesis analysis demonstrated that the data set of CPXM1 high expression was mainly enriched in cancer-related signal pathways. Conclusion CPXM1 is an effective biomarker for the prognosis of GC patients and may play a key role in the occurrence and progression of GC.

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The potential therapeutic actions of melatonin in colorectal cancer

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2019-0001 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 1

Author(s):

Kian Chung Chok ◽

Chew Hee Ng ◽

Rhun Yian Koh ◽

Khuen Yen Ng ◽

Soi Moi Chye

Keyword(s):

Colorectal Cancer ◽

Therapeutic Agent ◽

Melatonin Receptors ◽

Drug Synergy ◽

The Third ◽

Anticancer Effects ◽

Common Cancer ◽

The Relationship ◽

Comprehensive Reference

Abstract Colorectal cancer (CRC) is the third most common cancer and lethal disease worldwide. Melatonin, an indoleamine produced in pineal gland, shows anticancer effects on a variety of cancers, especially CRC. After clarifying the pathophysiology of CRC, the association of circadian rhythm with CRC, and the relationship between shift work and the incidence of CRC is reviewed. Next, we review the role of melatonin receptors in CRC and the relationship between inflammation and CRC. Also included is a discussion of the mechanism of gene regulation, control of cell proliferation, apoptosis, autophagy, antiangiogenesis and immunomodulation in CRC by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as comprehensive reference for the various mechanisms of action of melatonin against CRC, and as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for CRC.

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Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

JCO Precision Oncology ◽

10.1200/po.16.00015 ◽

2017 ◽

pp. 1-12

Author(s):

Manish R. Sharma ◽

James T. Auman ◽

Nirali M. Patel ◽

Juneko E. Grilley-Olson ◽

Xiaobei Zhao ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Somatic Mutation ◽

Mutation Rate ◽

Germ Line ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Response To Chemotherapy ◽

Cancer Genome Atlas ◽

Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

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Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

Mediators of Inflammation ◽

10.1155/2018/9853192 ◽

2018 ◽

Vol 2018 ◽

pp. 1-23 ◽

Cited By ~ 3

Author(s):

Amal Ahmed Abd El-Fattah ◽

Nermin Abdel Hamid Sadik ◽

Olfat Gamil Shaker ◽

Amal Mohamed Kamal

Keyword(s):

Colorectal Cancer ◽

Genetic Variation ◽

Sequence Variation ◽

Regulatory Protein ◽

Nucleotide Polymorphisms ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

The Third ◽

Common Cancer ◽

Cancer Initiation

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-βcan be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.

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The Prognostic Significance of MAFK and its Methylation in Cervical Cancer

10.21203/rs.3.rs-582069/v1 ◽

2021 ◽

Author(s):

Mengjun Zhang ◽

Hao Li ◽

Yuan Liu ◽

Siyu Hou ◽

Ping Cui ◽

...

Keyword(s):

Cervical Cancer ◽

Prognostic Significance ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Aberrant Methylation ◽

Cancer Data ◽

Drug Candidates ◽

Cancer Genome Atlas ◽

Cancer Tissues

Abstract Background: The purpose of this study was to determine the value of MAFK as a biomarker of cervical cancer prognosis and to explore its methylation and possible cellular signaling pathways. Methods: We analyzed the cervical cancer data of The Cancer Genome Atlas (TCGA) through bioinformatics, including MAFK expression, methylation, prognosis and genome enrichment analysis. Results: MAFK expression was higher in cervical cancer tissues and was negatively correlated with the methylation levels of five CpG sites. MAFK is an independent prognostic factor of cervical cancer and is involved in the Nod-like receptor signaling pathway. CMap analysis screened four drug candidates for cervical cancer treatment. Conclusions: We confirmed that MAFK is a novel prognostic biomarker for cervical cancer and aberrant methylation may also affect MAFK expression and carcinogenesis. This study provides a new molecular target for the prognostic evaluation and treatment of cervical cancer.

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Profile of Colorectal Tumor in Gastroentero-Hepatology Center, Department of Internal Medicine, Dr Soetomo Hospital, Surabaya

Folia Medica Indonesiana ◽

10.20473/fmi.v56i1.18445 ◽

2020 ◽

Vol 56 (1) ◽

pp. 15

Author(s):

Husin Thamrin ◽

Khafidhotul Ilmiah ◽

Ni Wajan Tirthaningsih

Keyword(s):

Colorectal Cancer ◽

Medical Records ◽

Colorectal Tumor ◽

Age And Gender ◽

Male And Female ◽

The Third ◽

Common Cancer ◽

Significant Difference ◽

And Gender ◽

Ethical Clearance

Colorectal cancer has became burden in the world.The latest study shows that colorectal cancer is the third most common cancer in men and second most common cancer in women globally. There are difference characteristic of epidemiology in every countries. Moreover, there is no study that represents epidemiology of colorectal cancer in Indonesia yet, especially in East Java. The aim of this study was to describe colorectal tumor profile by age and gender in Gastroentero-Hepatology Center, Dr Soetomo Hospital. This study has received a certificate of Ethical Clearance No.273/Panke.KKE/IV/2015, a descriptive retrospective study. We collected data using medical records, and patients who have been colonoscopy examination and suspected colorectal tumor were included. There were 201 patients, divided to 100 males and 101 females. The peak of incidence was on 51-60 years old group, but on the 31-40 years old incidence of colorectal tumor was increased. The youngest patient was 17 years old. And tumors are more likely develop in distal area, especially in rectum. This study shows a different characteristic profile of colorectal tumor, where tumor is developed at young people and there is no significant difference between male and female for the incidence.

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CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

10.21203/rs.3.rs-150866/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Jinguo Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Early Stage ◽

Human Tumor ◽

The Cancer Genome Atlas ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

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A Complicated Colorectal Cancer Recurrence

Acta Chirurgica Latviensis ◽

10.2478/chilat-2020-0006 ◽

2020 ◽

Vol 18 (1) ◽

pp. 25-27

Author(s):

Anna Marija Lescinska ◽

Valerija Grakova ◽

Aleksandrs Malasonoks ◽

Armands Sivins

Keyword(s):

Colorectal Cancer ◽

Case Report ◽

Cancer Recurrence ◽

Cancer Death ◽

Treatment Results ◽

Western Countries ◽

The Third ◽

Common Cancer ◽

One Step ◽

Colorectal Cancer Recurrence

SummaryThe case report demonstrates painstaking, one step at a time multitherapy for the third most common cancer and the third cause of cancer death in western countries – colorectal cancer. Multitherapeutic approach at specialized centers for the treatment of colorectal cancer is the cornerstone for reaching favorable treatment results and prognosis.

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