scholarly journals The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers

2021 ◽  
Vol 22 (3) ◽  
pp. 1354
Author(s):  
Linnea Hases ◽  
Ahmed Ibrahim ◽  
Xinsong Chen ◽  
Yanghong Liu ◽  
Johan Hartman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Machine Learning ◽  
Sex Differences ◽  
Tumor Tissue ◽  
Biomarker Discovery ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Normal Colon ◽  
Diagnostic Biomarkers ◽  
The Impact

Colorectal cancer (CRC) is the third leading cause of cancer deaths. Advances within bioinformatics, such as machine learning, can improve biomarker discovery and ultimately improve CRC survival rates. There are clear sex differences in CRC characteristics, but the impact of sex has not been considered with regards to CRC biomarkers. Our aim here was to investigate sex differences in the transcriptome of a normal colon and CRC, and between paired normal and tumor tissue. Next, we attempted to identify CRC diagnostic and prognostic biomarkers and investigate if they are sex-specific. We collected paired normal and tumor tissue, performed RNA-seq, and applied feature selection in combination with machine learning to identify the top CRC diagnostic biomarkers. We used The Cancer Genome Atlas (TCGA) data to identify sex-specific CRC diagnostic biomarkers and performed an overall survival analysis to identify sex-specific prognostic biomarkers. We found transcriptomic sex differences in both the normal colon tissue and in CRC. Forty-four of the top-ranked biomarkers were sex-specific and 20 biomarkers showed a sex-specific prognostic value. Our data show the importance of sex in the discovery of CRC biomarkers. We propose 20 sex-specific CRC prognostic biomarkers, including ESM1, GUCA2A, and VWA2 for males and CLDN1 and FUT1 for females.

scholarly journals CPEM: Accurate cancer type classification based on somatic alterations using an ensemble of a random forest and a deep neural network

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kanggeun Lee ◽  
Hyoung-oh Jeong ◽  
Semin Lee ◽  
Won-Ki Jeong
Keyword(s):  
Machine Learning ◽  
Prediction Model ◽  
Genomic Data ◽  
The Cancer Genome Atlas ◽  
Cancer Type ◽  
Machine Learning Classifiers ◽  
Learning Classifiers ◽  
Somatic Alterations ◽  
The Impact ◽  
Type Classification

AbstractWith recent advances in DNA sequencing technologies, fast acquisition of large-scale genomic data has become commonplace. For cancer studies, in particular, there is an increasing need for the classification of cancer type based on somatic alterations detected from sequencing analyses. However, the ever-increasing size and complexity of the data make the classification task extremely challenging. In this study, we evaluate the contributions of various input features, such as mutation profiles, mutation rates, mutation spectra and signatures, and somatic copy number alterations that can be derived from genomic data, and further utilize them for accurate cancer type classification. We introduce a novel ensemble of machine learning classifiers, called CPEM (Cancer Predictor using an Ensemble Model), which is tested on 7,002 samples representing over 31 different cancer types collected from The Cancer Genome Atlas (TCGA) database. We first systematically examined the impact of the input features. Features known to be associated with specific cancers had relatively high importance in our initial prediction model. We further investigated various machine learning classifiers and feature selection methods to derive the ensemble-based cancer type prediction model achieving up to 84% classification accuracy in the nested 10-fold cross-validation. Finally, we narrowed down the target cancers to the six most common types and achieved up to 94% accuracy.

scholarly journals Relevance of MicroRNAs as Potential Diagnostic and Prognostic Markers in Colorectal Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2944 ◽  
Author(s):  
Grzegorz Hibner ◽  
Małgorzata Kimsa-Furdzik ◽  
Tomasz Francuz
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Developed Countries ◽  
Prognostic Biomarkers ◽  
Screening Methods ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Mirna Expression Profiles ◽  
And Migration

Colorectal cancer (CRC) is currently the third and the second most common cancer in men and in women, respectively. Every year, more than one million new CRC cases and more than half a million deaths are reported worldwide. The majority of new cases occur in developed countries. Current screening methods have significant limitations. Therefore, a lot of scientific effort is put into the development of new diagnostic biomarkers of CRC. Currently used prognostic markers are also limited in assessing the effectiveness of CRC therapy. MicroRNAs (miRNAs) are a promising subject of research especially since single miRNA can recognize a variety of different mRNA transcripts. MiRNAs have important roles in epigenetic regulation of basic cellular processes, such as proliferation, apoptosis, differentiation, and migration, and may serve as potential oncogenes or tumor suppressors during cancer development. Indeed, in a large variety of human tumors, including CRC, significant distortions in miRNA expression profiles have been observed. Thus, the use of miRNAs as diagnostic and prognostic biomarkers in cancer, particularly in CRC, appears to be an inevitable consequence of the advancement in oncology and gastroenterology. Here, we review the literature to discuss the potential usefulness of selected miRNAs as diagnostic and prognostic biomarkers in CRC.

Sex differences in the impact of Affordable Care Act Medicaid expansion on colorectal cancer screening

2020 ◽  
Vol 138 ◽  
pp. 106171
Author(s):  
Kirsten Y. Eom ◽  
Marian Jarlenski ◽  
Robert E. Schoen ◽  
Linda Robertson ◽  
Lindsay M. Sabik
Keyword(s):  
Colorectal Cancer ◽  
Sex Differences ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Affordable Care Act ◽  
Medicaid Expansion ◽  
The Impact

scholarly journals Identification and verification of HCAR3 and INSL5 as new potential therapeutic targets of colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuan Yang ◽  
Wangao Wei ◽  
Shisheng Tan ◽  
Linrui Guo ◽  
Song Qiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Tumor Tissue ◽  
Therapeutic Targets ◽  
The Cancer Genome Atlas ◽  
Pcr Analysis ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Real Time Quantitative Pcr

Abstract Background Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and ranks third in cancer-related deaths worldwide. This study was conducted to identify novel biomarkers related to the pathogenesis of CRC based upon a bioinformatics analysis, and further verify the biomarkers in clinical tumor samples and CRC cell lines. Methods A series of bioinformatics analyses were performed using datasets from NCBI-GEO and constructed a protein–protein interaction (PPI) network. This analysis enabled the identification of Hub genes, for which the mRNA expression and overall survival of CRC patients data distribution was explored in The Cancer Genome Atlas (TCGA) colon cancer and rectal cancer (COADREAD) database. Furthermore, the differential expression of HCAR3 and INLS5 was validated in clinical tumor samples by Real-time quantitative PCR analysis, western blotting analysis, and immunohistochemistry analysis. Finally, CRC cells over-expressing INSL5 were constructed and used for CCK8, cell cycle, and cell apoptosis validation assays in vitro. Results A total of 286 differentially expressed genes (DEGs) were screened, including 64 genes with increased expression and 143 genes with decreased expression in 2 CRC database, from which 10 key genes were identified: CXCL1, HCAR3, CXCL6, CXCL8, CXCL2, CXCL5, PPY, SST, INSL5, and NPY1R. Among these genes, HCAR3 and INSL5 had not previously been explored and were further verified in vitro. Conclusions HCAR3 expression was higher in CRC tissues and associated with better overall survival of CRC patients. INSL5 expression in normal tissue was higher than that in tumor tissue and its high expression was associated with a better prognosis for CRC. The overexpression of INSL5 significantly inhibited the proliferation and promoted the shearing of PARP of CRC cells. This integrated bioinformatics study presented 10 key hub genes associated with CRC. HCAR3 and INSL5 were expressed in tumor tissue and these were associated with poor survival and warrant further studies as potential therapeutic targets.

Copy number variation and expression of CT-genes in patients with colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16104-e16104
Author(s):  
Yuriy A. Gevorkyan ◽  
Denis S. Kutilin ◽  
Oleg I. Kit ◽  
Natalya V. Soldatkina ◽  
Dmitry A. Kharagezov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Tumor Tissue ◽  
Malignant Tumors ◽  
Regulation Of Gene Expression ◽  
Rank Correlation ◽  
Normal Colon ◽  
Aberrant Expression ◽  
Spearman’S Rank Correlation

e16104 Background: Cancer-testis antigens (CTAs) can be used for immunotherapeutic approaches and early detection of malignant tumors. Despite numerous studies of CTA expression in various tumors, including colon tumors, the mechanisms of transcriptional activity regulation in colorectal cancer (CRC) remain poorly studied. One of the possible mechanisms of regulation of gene expression is a change in their copy number (CNV). The aim of the study was to analyze the changes in the copy number and expression of CT-genes in patients with CRC. Methods: Tumor and normal colon tissues of 81 patients were used in the study. DNA was isolated by phenol-chloroform extraction. RNA was isolated by the Chomczynski&Sacchi method (2006). The REVERTA-L reagent kit was used for the cDNA synthesis. Determination of expression and copy number of 16 CT genes ( MAGE-A1, -A2, -A3, -A4, MAGE-B1, -B2, GAGE-1, -3, -4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was performed using the Real-Time qPCR method (reference genes - GAPDH and GUSB). Differences were evaluated using the Mann-Whitney test, correlation analysis - using Spearman's rank correlation coefficient (r). Results: An analysis of CT-gene expression and CNV in tumor and normal colon tissues (n = 81) revealed a statistically significant (p < 0.05) difference between these parameters in tumor tissue relative to normal one: for MAGEB1 an increase of 2.0 and 2.7 times, GAGE3 an increase of 2.0 and 2.5 times, GAGE4 decreased by 5.0 and 6.8 times, BAGE decreased by 2.4 and 1.7 times, SSX2 increased by 1.8 and 2.1 times, SCP1 increased copy number by 4.4 times and PRAME1 increased expression and copy number by 2.9 and 2.3 times, respectively. When comparing CNV and expression of 16 CT genes, a positive correlation was observed (r = 0.875). Conclusions: Thus, the aberrant expression of MAGEB1, GAGE3, GAGE4, BAGE, SSX2 and PRAME1 found in the tumor tissue of CRC patients depends on the copy number of these CT-genes.

scholarly journals Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer

2021 ◽  
pp. jclinpath-2020-207309
Author(s):  
Kate Wilkinson ◽  
Weng Ng ◽  
Tara Laurine Roberts ◽  
Therese M Becker ◽  
Stephanie Hui-Su Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cytotoxic Chemotherapy ◽  
Response To Therapy ◽  
Prognostic Biomarkers ◽  
Surrounding Tissue ◽  
Immune Markers ◽  
Immune Microenvironment ◽  
Adaptive Immune ◽  
Response To Chemotherapy ◽  
The Impact

The role of the local tumour and stromal immune landscape is increasingly recognised to be important in cancer development, progression and response to therapy. The composition, function, spatial orientation and gene expression profile of the infiltrate of the innate and adaptive immune system at the tumour and surrounding tissue has an established prognostic role in colorectal cancer (CRC). Multiple studies have confirmed that a tumour immune microenvironment (TIME) reflective of a type 1 adaptive immune response is associated with improved prognosis. There have been significant efforts to evolve these observations into validated, histopathology-based prognostic biomarkers, such as the Immunoscore. However, the clinical need lies much more in the development of predictive, not prognostic, biomarkers which have the potential to improve patient outcomes. This is particularly pertinent to help guide cytotoxic chemotherapy use in CRC, which remains the standard of care. Cytotoxic chemotherapy has recognised immunomodulatory activity distinct from its antimitotic effects, including mechanisms such as immunogenic cell death (ICD) and induction/inhibition of key immune players. Response to chemotherapy may differ with regard to molecular subtype of CRC, which are strongly associated with immune phenotypes. Thus, immune markers are potentially useful, though under-reported, predictive biomarkers. In this review, we discuss the impact of the TIME on response to cytotoxic chemotherapy in CRC, with a focus on baseline immune markers, and associated genomic and transcriptomic signatures.

scholarly journals Immunonutrition Changes Inflammatory Response in Colorectal Cancer: Results from a Pilot Randomized Clinical Trial

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1444
Author(s):  
Mateusz Wierdak ◽  
Marcin Surmiak ◽  
Katarzyna Milian-Ciesielska ◽  
Mateusz Rubinkiewicz ◽  
Anna Rzepa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Nutritional Support ◽  
Tumor Tissue ◽  
Control Group ◽  
Preoperative Period ◽  
First Choice ◽  
Tnf Α ◽  
Oral Nutritional Supplements ◽  
Immune Group ◽  
The Impact

Introduction: Surgery is the first choice of treatment for colorectal cancer. Nutritional support in the form of oral nutritional supplements (ONSs) in the preoperative period is widely accepted for reducing the incidence of perioperative complications, and immunonutrition is generally recommended. However, there is little clinical data regarding the impact of such treatment on tumor biology. Material and Methods: In this study, tumor tissue and blood samples were collected from 26 patients during preoperative colonoscopy at the time of clinical diagnosis (sample A). Group 1 received standard ONSs (3× Nutricia Nutridrink Protein per day) for 2 weeks before surgery. In group 2, immune ONSs (2× Nestle Impact Oral) were administered for the same duration. Tumor tissue (sample B) was then retrieved from the tumor after resection. Changes in the expression levels of inflammatory cytokines (TNF-α, interleukin 8 or chemokine (C-X-C motif) ligand (CXCL8), stromal cell-derived factor 1 (SDF1a), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-X-C motif) ligand (CXCL2), myeloperoxidase (MPO), and CXCL1) were assessed during the perioperative course. Results: TNF-α expression differed after intervention between the two groups (immune group 31.63 ± 13.28; control group 21.54 ± 6.84; p = 0.049) and prior to and after intervention in the control group (prior to intervention 35.68 ± 24.41; after intervention 21.54 ± 6.84; p = 0.038). Changes in CXCL8 expression in the control group occurred prior to and after intervention (prior to intervention 2975.93 ± 1484.04; after intervention 1584.85 ± 1659.84; p = 0.041). CXCL1 expression was increased in the immune group and decreased in the control group (immune group 2698.27 (1538.14–5124.70); control group 953.75 (457.85–1534.60); p = 0.032). In both groups, a decrease in superficial neutrophil infiltration was observed, but this was only statistically significant in the immune group. There was no impact of the observed differences between the two groups on surgical outcomes (morbidity, length of stay, readmissions). Conclusions: Immunonutrition in the preoperative period compared with standard nutritional support may influence inflammatory cytokine expression and leukocyte infiltration in patients with colorectal cancer.

scholarly journals Novel Diagnostic Biomarkers in Colorectal Cancer

2022 ◽  
Vol 23 (2) ◽  
pp. 852
Author(s):  
Aneta L. Zygulska ◽  
Piotr Pierzchalski
Keyword(s):  
Colorectal Cancer ◽  
Somatic Mutations ◽  
Tumor Tissue ◽  
Locally Advanced ◽  
Survival Rates ◽  
High Sensitivity ◽  
Diagnostic Biomarkers ◽  
Blood Tests ◽  
Stool Samples ◽  
Endoscopic Methods

Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.

Hypermethylated promoters of genes UNC5D and KCNA1 as potential novel diagnostic biomarkers in colorectal cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1677-1688
Author(s):  
Sara Uhan ◽  
Nina Zidar ◽  
Aleš Tomažič ◽  
Nina Hauptman
Keyword(s):  
Colorectal Cancer ◽  
Candidate Genes ◽  
Promoter Hypermethylation ◽  
The Cancer Genome Atlas ◽  
Early Colorectal Cancer ◽  
Cancer Tissue ◽  
Promoter Regions ◽  
Diagnostic Biomarkers ◽  
Cancer Genome Atlas ◽  
Tissue Specimens

Aim: Identification of aberrant hypermethylation in promoter regions of candidate genes to discover potential biomarkers for colorectal cancer. Materials & Methods: Genes BMP2, IRF4, KCNA1, LRRC7, NRG3, SLC27A6 and UNC5D were pre-selected in a bioinformatics study for their hypermethylation status in colorectal cancer. Methylation analysis was performed on 202 cancer tissue specimens to validate candidate genes. Results: Genes KCNA1 and UNC5D displayed methylation in 95.3 and 99.7% of The Cancer Genome Atlas dataset samples and in 96 and 98% of our experimentally tested samples, respectively. Conclusion: KCNA1 and UNC5D promoter hypermethylation holds diagnostic biomarker potential in patients with early colorectal cancer.

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