scholarly journals Investigating the Relationship Between the Expression Level of Mucin Gene Cluster (MUC2, MUC5A, and MUC5B) and Clinicopathological Characterization of Colorectal Cancer

2021 ◽  
Vol 10 ◽  
pp. e2030
Author(s):  
Hossein Iranmanesh ◽  
Ahmad Majd ◽  
Ehsan Nazemalhosseini Mojarad ◽  
Mohammad Reza Zali ◽  
Mehrdad Hashemi
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Rna Extraction ◽  
Stage Iv ◽  
Diagnostic Value ◽  
Medical Sciences ◽  
Normal Tissues ◽  
Poorly Differentiated ◽  
Clinicopathological Variables

Background: Colorectal cancer (CRC) is one of the most common cancers in the world and has a high mortality rate. It is accepted that dysfunction in the expression of mucins are associated with the occurrence and development of CRC. Therefore, the present study aimed to investigate the expression of MUC2, MUC5A, and MUC5B genes in CRC and their relationship with clinicopathological variables. Materials and Methods: The population included 28 patients after a colonoscopy and confirmation of the results. Tumors and parallel adjacent normal tissues from CRC patients were collected. RNA extraction and cDNA synthesis were performed using the corresponding kits. The gene primer was designed and RT-PCR was used to evaluate gene expression. The t-test and ANOVA were used to examine the differences between the different groups. Data analysis was performed using Prism8 software. Tumors from CRC patients were retrospectively collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Results: The results showed that the expression of MUC2, MUC5A, and MUC5B genes was lower in patients with CRC aged 50 years or younger than was in older patients (P<0.05). Only the MUC5B gene expression was associated with tumor grades, which was higher in poorly differentiated tumors. The expression of MUC5A and MUC2 genes was higher in stage IV of the tumor than in other stages (P<0.05). Conclusion: Among the changes in the expression of MUC secretory genes, including MUC2, MUC5A, and MUC5B and clinicopathological variables, there was a relationship that could have prognostic and diagnostic value in CRC. [GMJ.2021;10:e2030]

MYC as a candidate upstream controller involved in TYMS gene expression and 5-FU/folate treatment efficacy in colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15512-e15512
Author(s):  
David A. Drubin ◽  
Anne-Katrin Hess ◽  
Natalie L. Catlett ◽  
Alessandro Di Cara ◽  
Yvonne Wettergren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Immune Cell ◽  
Stage Iv ◽  
Gene Signature ◽  
Immune Cell Population ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Classical Monocytes

e15512 Background: One of the target enzymes of 5-fluorouracil (5-FU)-based therapies is thymidylate synthase (TS) encoded by the TYMS gene. To enhance the effect of 5-FU, a folate analogue is often provided as part of the treatment. In this context, it has previously been shown in the ISO-CC-005 clinical study that TYMS gene expression can be predictive of response to 5-FU + folate analogue Arfolitixorin. Methods: To better understand the role of TYMS expression as a predictor of response to 5-FU + folate-based therapies and identify potential mechanisms and biomarkers of sensitivity/resistance, we leveraged data from the publicly available cancer genome atlas database (TCGA). We combined this information with a knowledgebase of causal biological relationships extracted from peer reviewed publications, to identify other relevant genes and candidate upstream controllers directly or indirectly related to TYMS expression and 5-FU + folate efficacy. Results: In TCGA subjects suffering from colorectal cancer (CRC) (stage IV tumors, treated with FOLFOX/FOLFIRI (n = 38)), lower TYMS expression was associated with a better overall survival (OS). This is consistent with what has been observed in the ISO-CC-005 study. Applying our causal biology knowledgebase to both genes identified as correlated to TYMS expression in TCGA CRC tumors and other published sets of genes associated with FOLFOX or FOLFIRI efficacy, we identified overlap with a MYCN signature. Notably MYC has been shown to directly activate TYMS expression. Thus, the MYC family is a compelling candidate upstream controller of these genes. We scored TCGA CRC tumors for inferred MYC activity, using this MYCN gene signature, and evaluated the inferred activity with respect to OS. In stage IV tumors, higher inferred MYC activity appears to be associated with worse OS. To further characterize this inferred MYC activity, we employed a transcriptomics-based cell deconvolution estimation of immune cell population proportions in the TCGA CRC cohort. We found inferred MYC activity inversely correlated with immune cell proportions overall, specifically strongest with those of pDCs and classical monocytes. Conclusions: MYC activation, a known transcriptional regulator of TYMS, has been identified as a potentially relevant common upstream controller of a group of genes involved in 5-FU + folate analogue efficacy. Here we have also observed a similar relationship to OS between TYMS and inferred MYC activity in Stage IV CRC. MYC family activity (and activated protein forms), genes of the MYCN signature, or the identified immune cell proportions are all potential biomarker candidates to explore as factors in 5-FU + folate analogue efficacy.

LncRNAs SNHG12 and LINC00152 were associated with progression of patients with papillary thyroid carcinoma

2019 ◽  
Vol 15 (36) ◽  
pp. 4167-4179 ◽  
Author(s):  
Jianqiu Liu ◽  
Xinyue Tang ◽  
Jing Lv ◽  
Xiaowei Peng ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Papillary Thyroid Carcinoma ◽  
Operating Characteristic ◽  
Thyroid Nodules ◽  
Diagnostic Value ◽  
Gene Expression Omnibus ◽  
Papillary Thyroid ◽  
Normal Tissues ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Aim: To investigate the clinical roles of LINC00152 and SNHG12 in papillary thyroid carcinoma (PTC). Methods: LINC00152 and SNHG12 expression was sought and analysis in gene expression omnibus, The Cancer Genome Atlas and GEPIA datasets. Tumor and adjacent normal tissues were collected from 97 PTC and 44 benign thyroid nodules patients. The expression was evaluated by quantitative real-time polymerase chain reaction. The association between the expression level and clinicopathologic characteristics was analyzed by χ2 test. Receiver operating characteristic curves were plotted to evaluate the diagnostic value. Results: The expression of SNHG12 and LINC00152 were significantly higher in PTC tissues than in adjacent normal tissues not only in gene expression omnibus database but the validated samples. More interesting, LINC00152 expression level was also significantly higher in PTC tissues than that in benign thyroid nodules. The upregulation of LINC00152 and SNHG12 was associated with the malignant progression of PTC. Receiver operating characteristic curve analysis also demonstrated that there was a good trend, which indicates that they may have certain diagnostic value. Conclusion: LINC00152 and SNHG12 might serve as serve as potential related molecules of PTC.

Validation of a microarray-based gene expression test for tumors with uncertain origins using formalin-fixed paraffin-embedded (FFPE) specimens

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22015-e22015
Author(s):  
R. Pillai ◽  
R. Deeter ◽  
C. T. Rigl ◽  
M. Halks-Miller ◽  
W. D. Henner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Extraction ◽  
Human Tumor ◽  
Data File ◽  
Similarity Score ◽  
Accurate Estimate ◽  
Tumor Type ◽  
Test Panel ◽  
Poorly Differentiated ◽  
Tissue Of Origin

e22015 Background: Microarray-based gene expression has been validated as an aid in the diagnosis of tumors with uncertain origins when the specimen is frozen tissue. Microarray use has been largely limited to RNA derived from frozen specimens. This study evaluated performance of a microarray-based test in identifying the tumor type in FFPE specimens. Methods: ZFFPE human tumor specimens (n=405) representing the 15 tissue of origin sites on the Pathwork® Tissue of Origin Test panel were blinded and evenly distributed between two independent processing labs. All specimens consisted of a 10-μm-paraffin curl containing at least 60% viable tumor and were either metastatic or poorly differentiated primaries. Each specimen was processed through RNA extraction, amplification, labeling, hybridization to a Pathchip® microarray, and was scanned to generate a qualified data file. A pre-specified classification algorithm utilizing more than 1500 genes was applied to each data file to yield Similarity Scores corresponding to the 15 tissues on the test panel. Results were then unblinded and compared to the available diagnoses. Results: Of the 405 specimens, 352 yielded qualified data files (87%). Based on the top Similarity Score, the overall agreement with available diagnoses was 89% (95% CI, 85%-92%) and for each specimen an average of 12 out of 15 tissues could be ruled out with > 99% probability. Results for all tissue types were highly informative with diagnostic odds ratios ranging from 178 to 28509. Performance was similar for metastatic (n=150; 91% agreement) and poorly differentiated primary specimens (n=202; 87% agreement). Conclusions: The large size of this study allows an accurate estimate of the confidence of test predictions for both ruling in and ruling out tissues as likely sites of primary origin. The Pathwork Tissue of Origin Test makes the potential benefits of microarray-based gene expression tests for tumors with uncertain origins available for use with the most common type of histology specimen, FFPE. [Table: see text]

scholarly journals Histopathological finding as a prognostic factor of the surgical treatment outcome in colorectal cancer

2010 ◽  
Vol 67 (8) ◽  
pp. 638-643 ◽  
Author(s):  
Svetozar Secen ◽  
Nebojsa Moljevic ◽  
Milivoje Vukovic ◽  
Ljiljana Somer
Keyword(s):  
Colorectal Cancer ◽  
Treatment Outcome ◽  
Prognostic Factors ◽  
Surgical Treatment ◽  
Tnm Classification ◽  
Stage Iv ◽  
Histological Structure ◽  
Poorly Differentiated ◽  
The Impact ◽  
Stage D

Background/Aim. Adenocarcinomas of the colon are the most common malignant colorectal tumors. Macroscopic and histopahtological features of colorectal cancer significantly affect its outcome. The aim of this study was to analyze the impact of histopahological finding as a prognostic factor on the surgical treatment outcome and the course of the disease. Methods. In the first part of this study the distribution (numerical and proportional) of certain histopathological parameters in the examined groups of patients were reviewed; in the second part of the study the statistical significance of the impact of the certain elements of a histopahtological finding on the surgical treratment outcome was analyzed. The histopathological elements analyzed included: the hsitological tumor type grading according to Duke, ie Astler-Coller, and tumor, nodes, metastases (TNM) staging in the examined sample of 100 patients. Results. Statistically significant prognostic factors of the outcome of surgical treatment were selected after multivariant analysis. These factors comprise Astler-Coller-Dukes stage D (revealed in 77.78% patients died), stage IV according TNM classification (T1-4, N0-2, M1), histological structure (poorly diferentiated adenocarcinoma in 85.2% patents died) and type of tumor (mucynous adenocarcinoma was more often present in died, 77.78%). Since ? = 0.000 for four risk factors were formed using discriminant analysus, it was proved their significant influence on the outcome of surgical treatment. Discriminant coefficient showed that the greatest influence on surgical treatment were registred in patients with tumor of Astler-Coller-Dukes stage D (0.255), poorly differentiated adenocarcinoma (histological structure) (0.139), mucynous adenocarcinoma (type of tumor) (0.074) and stage IV according to the TNM elassification (T1-4, N0-2, M1) (0.39). Conclusion. The prognostic factors influencing the outcome of surgery for colorectal carcinoma were defined. Patients with pathohistological finding of Astler-Coller-Dukes stage D, stage IV according to the TNM classification (T1-4, N0-2, M1) and poorly differentiated adenocarcioma have statistically highly significant mortality during the perioperative course of the disease.

scholarly journals Potential Prognosis and Diagnostic Value of AKT3, LSM12, MEF2C, and RAB30 in Exosomes in Colorectal Cancer on Spark Framework

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jue Wang ◽  
Sheng Wu ◽  
Jiuwen Zhang ◽  
Jing Chen
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Cancer Metastasis ◽  
Diagnostic Value ◽  
Functional Enrichment ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Proposed Model ◽  
Tcga Dataset

Colorectal cancer (CRC) is a common malignant tumor and one of the leading causes of cancer-related deaths worldwide. CRC progression is greatly affected by the local microenvironment. In the study, we proposed a deep computational-based model for the classification of mRNA, lncRNA, and circRNA in exosomes. We, first, analyzed mRNA expression levels in CRC tumors and normal tissues. Secondly, we used GO and KEGG to analyze their functional enrichment. Thirdly, we analyzed the composition of immune cells in all TCGA samples and then evaluated the prognostic value of tumor-infiltrating immune cells in CRC. Lastly, we combined the TCGA dataset, i.e., COADN = 449 and ROADN = 6, for analysis and found that the expression levels of AKT3, LSM12, MEF2C, and RAB30 in exosomes were significantly correlated with tumor immune infiltration levels. The performance evaluation has shown that the proposed model based on neural networks performs better as compared to the existing methods. The proposed model can be used as a potential tool for the immune infiltration level and their role in cancer metastasis and progression, which can help us to explore potential strategies for CRC diagnosis, therapy, and prognosis.

Pharmacogenomic analysis for individual response to CPT-11 in colorectal cancer: Prediction formula of tumor response using novel marker genes and genotypes associated with the toxicity

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2060-2060
Author(s):  
H. Narahara ◽  
N. Sugimoto ◽  
N. Tomita ◽  
K. Murata ◽  
M. Fukunaga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tumor Response ◽  
Stage Iv ◽  
Clinical Samples ◽  
Marker Genes ◽  
Individual Response ◽  
Expression Data ◽  
Prediction Formula

2060 Background: Despite recent encouraging data, the clinical efficacy and toxicity of CPT-11 in most colorectal cancer patients remain unpredictable. We conducted this prospective study to develop a prediction formula of efficacy using expression data of genes newly identified in vitro and to evaluate the clinical significance of several genetic polymorphisms known as potent predictors of toxicity. Methods: CPT-11 was intravenously administered on Days 1, 8, and 15, every 4 weeks in chemo-naive patients with stage IV colorectal cancer after palliative operation. Tumor samples were collected at surgery and PK analysis was done on day 1 of cycle 1. Tumor response and toxicity were evaluated by RECIST and CTCAE, respectively. Results: Forty seven pts were enrolled. All pts were assessed for tumor response, toxicity, gene expression, genotype, and PK. Partial response was obtained in 11 cases, and common grade 3/4 toxicities were neutropenia (15%), leucopenia (5%), and diarrhea (4%). Despite no correlation of UGT1A1*28 (hetero=5, homo=1) alone with the toxicities, there were associations between UGT1A1*28 or *7 (hetero=1) with UGT1A1 -64G>C (hetero=3) and G3/4 leucopenia (p=0.036). UGT1A1 1091C>T (hetero=3) was found to be associated with leucopenia (p=0.0009), neutropenia (p=0.012), and diarrhea (p=0.036). UGT1A1 1091C>T, ABCC2 -24C>T and 3972C>T were correlated with SN-38 AUC. We identified 7 novel potent marker genes including AMD1, CTSC, and EIF1AX for CPT-11 efficacy in vitro, through 2 different microarray analyses and subsequent real-time RT-PCR. We then successfully developed the best linear model, which converted the quantified expression data into objective tumor response, using 18 data sets of gene expression and clinical response. Utility-confirmation analyses using other clinical samples appeared to show that the formula could accurately predict tumor response (r=0.712, p=0.042). Conclusions: Polygenetic strategies using several known polymorphisms for toxicity and a prediction formula using 7 novel genes for efficacy would be of predictive value for individual response to CPT-11. No significant financial relationships to disclose.

scholarly journals Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues

2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Messenger Rna ◽  
Stage Iv ◽  
Mrna Levels ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
The Relationship ◽  
Neoplastic Tissues

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.

Correlations of Bcl-2 and Survivin Gene Protein Expressions in Colorectal Cancer

2013 ◽  
Vol 423-426 ◽  
pp. 362-365 ◽  
Author(s):  
Yue Ma ◽  
Hong Sheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Normal Tissues ◽  
Positive Expression ◽  
Significant Difference ◽  
Protein Expressions ◽  
Positive Rate ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues

Objective: In this study, immunohistochemical streptavidinbiotin-peroxidase (S-P method) was used to detect the correlation of gene proteins related to apoptosis, such as Bcl-2 and Survivin in colorectal carcinoma. Methods: Pathological specimens from 46 colorectal cancer patients and 8 normal tissues around the tumor specimens were selected. Immunohistochemical streptavidin-biotin-peroxidase assay was used to detect the expression of Bcl-2 and Surviving protein. Results: In 25 cases of Bcl-2 positive expression, there were 24 cases of Survivin positive expression, accounting for 96%; while there were 8 cases of Survivin positive expression in 21 cases of Bcl-2 negative expression, accounting for 38.1%, showing the expression of Bcl-2 and the expression of Survivin was positively correlated (Pearsons R= 0.627, P<0.01). In 15 cases of well-differentiated colorectal cancer tissues, there were 6 Cases of Survivin positive expression, and the positive rate was 40%; in 17 cases of moderately differentiated colorectal cancer tissues, there were 17 cases, and the positive rate was 100%; in 14 cases of poorly differentiated colorectal cancer tissues, there were 9 cases, and the positive rate was 64.29%. The statistical analysis showed that the Survivin positive expression in the three colorectal cancer tissues presented a significant difference (P <0.01). Results: The positive expression of Survivin protein was directly correlated to that of Bcl-2, which suggested that both of them acted on different stages of apoptosis to promote jointly the development of colorectal cancer in a synergistic way.

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