Overexpression of EphA4 gene and reduced expression of EphB2 gene: Correlation with liver metastasis in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15129-e15129
Author(s):  
T. Oshima ◽  
N. Yamamoto ◽  
T. Sato ◽  
Y. Nagano ◽  
S. Fujii ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Tyrosine Kinases ◽  
Large Family ◽  
Cancer Tissue ◽  
Eph Receptors ◽  
Expression Levels ◽  
Relative Expression ◽  
Over Expression

e15129 The Eph receptors, members of a large family of transmembrane receptor tyrosine kinases, play important roles in a variety of biologic functions. Recent studies have suggested that EphA4 and EphB2 participate in the growth and development of various carcinomas. This study examined the relations of EphA4 and EphB2 gene expression to clinicopathological factors, especially metastasis, in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal cancer. The relative expression levels of EphA4 and EphB2 mRNA in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. The relative expression level of EphA4 mRNA was higher in the presence than in the absence of liver metastasis, whereas the relative expression levels of EphB2 mRNA were similar. Analysis of the relations between clinicopathological features and gene expression showed that high expression of the EphA4 gene and low expression of the EphB2 gene correlated with liver metastasis. There was no correlation between EphA4 and EphB2 gene expression. Our results suggest that over-expression of the EphA4 gene and reduced expression of the EphB2 gene might promote liver metastasis in colorectal cancer. Over-expression of the EphA4 gene and reduced expression of the EphB2 gene may thus be a useful predictor of liver metastasis in patients with colorectal cancer. No significant financial relationships to disclose.

scholarly journals 5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis

2006 ◽  
Vol 119 (3) ◽  
pp. 522-526 ◽  
Author(s):  
Hidekazu Kuramochi ◽  
Kazuhiko Hayashi ◽  
Kazumi Uchida ◽  
Satoru Miyakura ◽  
Daisuke Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Related Gene ◽  
Primary Colorectal Cancer ◽  
Expression Levels ◽  
Gene Expression Levels

TIMP-1 Expression in Human Colorectal Cancer Is Associated with SMAD3 Gene Expression Levels: A Pilot Study

2014 ◽  
Vol 23 (4) ◽  
pp. 413-418 ◽  
Author(s):  
Calin Ionescu ◽  
Cornelia Braicu ◽  
Roxana Chiorean ◽  
Roxana Cojocneanu Petric ◽  
Emilian Neagoe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tumor Tissue ◽  
Transforming Growth Factor ◽  
Prognostic Significance ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Qrt Pcr ◽  
E Cadherin

Background & Aims: The prognosis of colorectal cancer (CRC) varies considerably, and there is a compelling need to identify novel biomarkers with prognostic significance. The aim of the present study was to evaluate the prognostic value of a panel of six genes (CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12) in CRC patients.Methods. We evaluated these genes by qRT-PCR in normal and CRC tumor tissue, and correlated the relative gene expression values with clinical, pathological aspects and other biological factors.Results. RNA expression levels of CDH1, SMAD3, TGFβ1, ICAM-1, TIMP-1 and MUC12 were measured by qRT-PCR in a set of 39 tumor samples and non-cancer tissue. Statistically significant increases in expression levels were found for ICAM-1 and TIMP-1 when comparing tumor samples to the non-tumor group.Conclusions. Among the genes which displayed differential expressions between tumor tissue and adjoining normal tissue, the ones that presented statistically significant correlations were TIMP-1 and SMAD3, possibly with prognostic significance.Abbreviations: CDH1: E-cadherin; CRC: colorectal cancer; E-cadherin: CDH1; EMT: epithelial-mesenchymal transition; IBD: inflammatory bowel disease; ICAM-1: Intercellular Adhesion Molecule 1; MMPs: matrix metalloproteinases; MUC12: Mucin 12, Cell Surface Associated; OS: overall survival; SMAD3: SMAD Family Member; TGFß1: Transforming growth factor beta 1; TIMP-1: tissue inhibitor of metalloproteinase-1.

scholarly journals Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature

2021 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
Noshad Peyravian ◽  
Stefania Nobili ◽  
Zahra Pezeshkian ◽  
Meysam Olfatifar ◽  
Afshin Moradi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Candidate Genes ◽  
Case Series ◽  
Gene Expression Signature ◽  
Gene Panel ◽  
Expression Levels ◽  
Node Metastasis

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.

scholarly journals The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Data ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lymphatic Vessels ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cancer Tissue ◽  
Expression Levels

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

scholarly journals Uncovering Potential Therapeutic Targets in Colorectal Cancer by Deciphering Mutational Status and Expression of Druggable Oncogenes

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 983 ◽  
Author(s):  
Otília Menyhart ◽  
Tatsuhiko Kakisaka ◽  
Lőrinc Sándor Pongor ◽  
Hiroyuki Uetake ◽  
Ajay Goel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gene Expression Data ◽  
Drug Targets ◽  
Therapeutic Targets ◽  
Independent Set ◽  
Driver Mutations ◽  
Expression Data ◽  
Expression Levels ◽  
Mutational Status

Background: Numerous driver mutations have been identified in colorectal cancer (CRC), but their relevance to the development of targeted therapies remains elusive. The secondary effects of pathogenic driver mutations on downstream signaling pathways offer a potential approach for the identification of therapeutic targets. We aimed to identify differentially expressed genes as potential drug targets linked to driver mutations. Methods: Somatic mutations and the gene expression data of 582 CRC patients were utilized, incorporating the mutational status of 39,916 and the expression levels of 20,500 genes. To uncover candidate targets, the expression levels of various genes in wild-type and mutant cases for the most frequent disruptive mutations were compared with a Mann–Whitney test. A survival analysis was performed in 2100 patients with transcriptomic gene expression data. Up-regulated genes associated with worse survival were filtered for potentially actionable targets. The most significant hits were validated in an independent set of 171 CRC patients. Results: Altogether, 426 disruptive mutation-associated upregulated genes were identified. Among these, 95 were linked to worse recurrence-free survival (RFS). Based on the druggability filter, 37 potentially actionable targets were revealed. We selected seven genes and validated their expression in 171 patient specimens. The best independently validated combinations were DUSP4 (p = 2.6 × 10−12) in ACVR2A mutated (7.7%) patients; BMP4 (p = 1.6 × 10−04) in SOX9 mutated (8.1%) patients; TRIB2 (p = 1.35 × 10−14) in ACVR2A mutated patients; VSIG4 (p = 2.6 × 10−05) in ANK3 mutated (7.6%) patients, and DUSP4 (p = 7.1 × 10−04) in AMER1 mutated (8.2%) patients. Conclusions: The results uncovered potentially druggable genes in colorectal cancer. The identified mutations could enable future patient stratification for targeted therapy.

scholarly journals Prospective validation in epithelial tumors of a gene expression predictor of liver metastasis derived from uveal melanoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Petros Tsantoulis ◽  
Mauro Delorenzi ◽  
Ivan Bièche ◽  
Sophie Vacher ◽  
Pascale Mariani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Uveal Melanoma ◽  
Meta Analysis ◽  
Prognostic Score ◽  
Penalized Regression ◽  
Breast Cancer Patients ◽  
Public Data

AbstractPredicting the risk of liver metastasis can have important prognostic and therapeutic implications, given the availability of liver-directed therapy. Uveal melanoma has a striking predisposition for liver metastasis despite the absence of anatomical proximity. Understanding its biology may uncover factors promoting liver metastasis in other malignancies. We quantified gene expression by RNAseq in 76 uveal melanomas and combined with public data in a meta-analysis of 196 patients. The meta-analysis of uveal melanoma gene expression identified 63 genes which remained prognostic after adjustment for chromosome 3 status. Two genes, PTP4A3 and JPH1, were selected by L1-penalized regression and combined in a prognostic score. The score predicted liver-specific relapse in a public pan-cancer dataset and in two public colorectal cancer datasets. The score varied between colorectal consensus molecular subtypes (CMS), as did the risk of liver relapse, which was lowest in CMS1. Additional prospective validation was done by real-time PCR in 463 breast cancer patients. The score was significantly correlated with liver relapse in hormone receptor positive tumors. In conclusion, the expression of PTP4A3 and JPH1 correlates with risk of liver metastasis in colorectal cancer and breast cancer. The underlying biological mechanism is an interesting area for further research.

Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mrna Expression ◽  
Advanced Colorectal Cancer ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Expression Levels ◽  
Mutational Status ◽  
Mrna Expression Levels ◽  
Gene Expression Levels

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.

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