scholarly journals Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival

10.1186/gm248 ◽  
2011 ◽  
Vol 3 (5) ◽  
pp. 32 ◽  
Author(s):  
Anita Sveen ◽  
Trude H Ågesen ◽  
Arild Nesbakken ◽  
Torleiv O Rognum ◽  
Ragnhild A Lothe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Splicing Factor ◽  
Expression Levels ◽  
Factor Expression ◽  
Microarray Analyses ◽  
Exon Microarray

scholarly journals High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer

2014 ◽  
Vol 1 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Seán Fitzgerald ◽  
Katherine M Sheehan ◽  
Virginia Espina ◽  
Anthony O'Grady ◽  
Robert Cummins ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Signalling Pathways ◽  
Expression Levels

508 Identification of Fusion Transcripts in Colorectal Cancer by Combined RNA-seq and Exon Microarray Analyses

2012 ◽  
Vol 48 ◽  
pp. S121
Author(s):  
R. Skotheim ◽  
T. Nome ◽  
G.O.S. Thomassen ◽  
B. Johannessen ◽  
A.C. Bakken ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rna Seq ◽  
Fusion Transcripts ◽  
Microarray Analyses ◽  
Exon Microarray

scholarly journals YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance

2021 ◽  
Vol 22 (16) ◽  
pp. 8481
Author(s):  
Silvia Vivarelli ◽  
Luca Falzone ◽  
Saverio Candido ◽  
Benjamin Bonavida ◽  
Massimo Libra
Keyword(s):  
Colorectal Cancer ◽  
Response To Therapy ◽  
Advanced Stage ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Single Cell Sequencing ◽  
Yin Yang 1 ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Colorectal cancer (CRC) is characterized by genetic heterogeneity and is often diagnosed at an advanced stage. Therefore, there is a need to identify novel predictive markers. Yin Yang 1 (YY1) is a transcription factor playing a dual role in cancer. The present study aimed to investigate whether YY1 expression levels influence CRC cell response to therapy and to identify the transcriptional targets involved. The diagnostic and prognostic values of YY1 and the identified factor(s) in CRC patients were also explored. Silencing of YY1 increased the resistance to 5-Fluorouracil-induced cytotoxicity in two out of four CRC cells with different genotypes. BCL2L15/Bfk pro-apoptotic factor was found selectively expressed in the responder CRC cells and downregulated upon YY1 knockdown. CRC dataset analyses corroborated a tumor-suppressive role for both YY1 and BCL2L15 whose expressions were inversely correlated with aggressiveness. CRC single-cell sequencing dataset analyses demonstrated higher co-expression levels of both YY1 and BCL2L15 within defined tumor cell clusters. Finally, elevated levels of YY1 and BCL2L15 in CRC patients were associated with larger relapse-free survival. Given their observed anti-cancer role, we propose YY1 and BCL2L15 as candidate diagnostic and prognostic CRC biomarkers.

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 loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy

Oncogene ◽  
2021 ◽  
Author(s):  
Jian Chen ◽  
Risi Na ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Serine Hydroxymethyltransferase ◽  
First Line ◽  
Xenograft Models ◽  
Potential Opportunity ◽  
First Line Treatment ◽  
Novel Therapeutic

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.

scholarly journals Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jun You ◽  
Jiayi Li ◽  
Chunlin Ke ◽  
Yanru Xiao ◽  
Chuanhui Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Noncoding Rna ◽  
Cell Function ◽  
In Vivo Studies ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Clinical Biomarkers ◽  
Tumor Tissues

AbstractEmerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.

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 Tissue factor expression is associated with recurrence in patients with non-metastatic colorectal cancer

2018 ◽  
Vol 14 (2) ◽  
pp. 128-134
Author(s):  
Hee Jae Jung ◽  
Hye Jin Kim ◽  
Kensuke Kaneko ◽  
Yoshihiro Kazama ◽  
Kazushige Kawai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Expression
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