Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma

Busuioc, Constantin; Ciocan-Cârtiţă, Cristina Alexandra; Braicu, Cornelia; Zănoagă, Oana; Ráduly, Lajos; Trif, Monica; Muresan, Mihai-Stefan; Ionescu, Călin; Stefan, Cristina; Crivii, Carmen; Hajjar, Nadim Al; Mărgărit, Simona; Berindan‐Neagoe, Ioana

doi:10.3390/jpm11060476

Cited by 10 publications

(7 citation statements)

References 58 publications

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“…Significantly downregulated genes in Tks4 KO cells include EHF, RERG, MMP13, MMP14, BMP5, and DLC1 ( Figure 2 C). These genes are involved in epithelial differentiation and proliferation [ 40 ] and tumor development, with low expression connected to poor prognosis [ 41 , 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

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Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

Jacksi

Schád

Buday

et al. 2023

IJMS

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Tks4 is a large scaffold protein in the EGFR signal transduction pathway that is involved in several cellular processes, such as cellular motility, reactive oxygen species-dependent processes, and embryonic development. It is also implicated in a rare developmental disorder, Frank–ter Haar syndrome. Loss of Tks4 resulted in the induction of an EMT-like process, with increased motility and overexpression of EMT markers in colorectal carcinoma cells. In this work, we explored the broader effects of deletion of Tks4 on the gene expression pattern of HCT116 colorectal carcinoma cells by transcriptome sequencing of wild-type and Tks4 knockout (KO) cells. We identified several protein coding genes with altered mRNA levels in the Tks4 KO cell line, as well as a set of long non-coding RNAs, and confirmed these changes with quantitative PCR on a selected set of genes. Our results show a significant perturbation of gene expression upon the deletion of Tks4, suggesting the involvement of different signal transduction pathways over the well-known EGFR signaling.

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Section: Resultsmentioning

confidence: 99%

“…BMP5 (bone morphogenetic protein 5) downregulation has been implicated in the EMT processes in colon adenocarcinoma [ 42 ]. Its significant downregulation in Tks4 KO cells underlines the pro-EMT phenotype induced by the deletion of Tks4.…”

Section: Discussionmentioning

confidence: 99%

Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

Jacksi

Schád

Buday

et al. 2023

IJMS

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“…A significant portion of the genes was already linked to colorectal cancer pathogenesis or progression/prognosis by previous studies. For example, expression levels, deletion, or biological functions of ROR2, SFRP1, LRP6, PITX2, WLS, GPC1, HCK, HPN, MKRN2, and DDX58 were associated with disease features, patient outcomes/prognosis, or invasive and other malignant features of colorectal tumors (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). This literature information supports our findings and can be partly attributed to the fact that the Wnt pathway is one of the most studied pathways in colorectal cancer, increasing the chances of finding literature information on genes functioning in Wnt-related biological processes.…”

Section: Discussionmentioning

confidence: 99%

Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer

Curtis

Yu²,

Carey³

et al. 2023

Front. Oncol.

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BackgroundInteractions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes.ObjectivesIn this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients.Methods423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included. Five Wnt family member proteins (Wnt1, Wnt2, Wnt5a, Wnt5b, and Wnt11) were selected. The BioGRID database was used to identify the proteins interacting with each of these proteins. Genotypes of the SNPs located in the interaction network genes were retrieved from a genome-wide SNP genotype data previously obtained in the patient cohort. The GMDR 0.9 program was utilized to examine 1-, 2-, and 3-SNP interactions using a 5-fold cross validation step. Top GMDR 0.9 models were assessed by permutation testing and, if significant, prognostic associations were verified by multivariable logistic regression models.ResultsGMDR 0.9 has identified novel 1, 2, and 3-way SNP interactions associated with 5-year recurrence risk in colorectal cancer. Nine of these interactions were multi loci interactions (2-way or 3-way). Identified interaction models were able to distinguish patients based on their 5-year recurrence-free status in multivariable regression models. The significance of interactions was the highest in the 3-SNP models. Several of the identified SNPs were eQTLs, indicating potential biological roles of the genes they were associated with in colorectal cancer recurrence.ConclusionsWe identified novel interacting genetic variants that associate with 5-year recurrence risk in colorectal cancer. A significant portion of the genes identified were previously linked to colorectal cancer pathogenesis or progression. These variants and genes are of interest for future functional and prognostic studies. Our results provide further evidence for the utility of GMDR models in identifying novel prognostic biomarkers and the biological importance of the Wnt pathways in colorectal cancer.

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“…In different types of solid tumors, researchers have indicated the implications of HIF-1α in the regulation of EMT transcription factors, enzymes (e.g., lysyl oxidase (LOX)), MMPs (such as collagenase MMP1 and gelatinase MMP2), histone modifiers (e.g., histone lysine-specific demethylase 4B (KDM4B)), adhesion molecules (e.g., angiopoietin-like 4 (ANGPTL4), L1 cell adhesion molecule (L1CAM)), chemokine receptors 1 and 4 (CX3CR1, CXCR4), and miRNA targets to stimulate tumor progression and invasion [ 148 , 149 ].…”

Section: Hypoxiamentioning

confidence: 99%

Multiple Faces of the Glioblastoma Microenvironment

Şovrea

Boşca

Melincovici

et al. 2022

IJMS

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The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.

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Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma

Cited by 10 publications

References 58 publications

Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer

Multiple Faces of the Glioblastoma Microenvironment

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