A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer

Yu, Yajun; Werdyani, Salem; Carey, Megan E; Parfrey, Patrick S.; Yilmaz, Yildiz E.; Savas, Sevtap

doi:10.1002/1878-0261.13067

Cited by 12 publications

(7 citation statements)

References 101 publications

(200 reference statements)

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“…PCOLCE2 has been identified as a biomarker in multiple cancers, including colorectal and gastric cancers (L. Xu et al, 2021). ERP27 is highly expressed in colorectal cancers, and its expression is correlated with patient survival (Yu et al, 2021). PSMD13 expression in lung adenocarcinoma strongly correlates with PSMC6 expression, which is associated with poor tumor differentiation and might act as a therapeutic target in lung adenocarcinoma (Zhang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

et al. 2022

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Background: Studies have suggested that glioblastoma (GBM) cells originate from the subventricular zone (SVZ) and that GBM contact with the SVZ correlated with worse prognosis and higher recurrence. However, research on differentially expressed genes (DEGs) between GBM and the SVZ is lacking.Methods: We performed deep RNA sequencing on seven SVZ-involved GBMs and paired tumor-free SVZ tissues. DEGs and enrichment were assessed. We obtained GBM patient expression profiles and clinical data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the CGGA cohort. GBM patient data from TCGA cohort were used for validation.Results: We identified 137 (97 up- and 40 down-regulated) DEGs between GBM and healthy SVZ samples. Enrichment analysis revealed that DEGs were mainly enriched in immune-related terms, including humoral immune response regulation, T cell differentiation, and response to tumor necrosis factor, and the MAPK, cAMP, PPAR, PI3K-Akt, and NF-κb signaling pathways. An eight-gene (BCAT1, HPX, NNMT, TBX5, RAB42, TNFRSF19, C16orf86, and TRPC5) signature was constructed. GBM patients were stratified into two risk groups. High-risk patients showed significantly reduced overall survival compared with low-risk patients. Univariate and multivariate regression analyses indicated that the risk score level represented an independent prognostic factor. High risk score of GBM patients negatively correlated with 1p19q codeletion and IDH1 mutation. Immune infiltration analysis further showed that the high risk score was negatively correlated with activated NK cell and monocyte counts, but positively correlated with macrophage and activated dendritic cell counts and higher PD-L1 mRNA expression.Conclusion: Here, a novel gene signature based on DEGs between GBM and healthy SVZ was developed for determining GBM patient prognosis. Targeting these genes may be a therapeutic strategy for GBM.

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Section: Discussionmentioning

confidence: 99%

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

et al. 2022

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“…CLDN2 expression contributes to chemoresistance in CRC cells and is associated with poor outcomes in patients with CRC (48,49). ERP27 is an endoplasmic reticulum protein, and the gene is highly expressed in patients with CRC (50). IFIT1 is an interferonstimulated inflammation-related protein that promotes cell invasion, metastasis, and tumor development (51).…”

Section: Discussionmentioning

confidence: 99%

Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol

Yokoyama

Kushibiki

Yamada

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Fucoxanthinol (FxOH), a marine carotenoid, induces apoptosis and anoikis in human colorectal cancer (CRC) DLD-1 cells via the down-regulation of chloride intracellular channel 4 (CLIC4) expression, a key molecule for apoptosis. However, whether FxOH is susceptible to CLIC4 expression and its regulatory mechanisms in human CRC cells remains unknown. We investigated the inhibitory effects of FxOH on six types of human CRC cells with CLIC4 regulation. Materials and Methods: The association between FxOH and CLIC4 was investigated using gene knockdown, overexpression, and transcriptome analyses. Results: CLIC4 expression in CRC cells was a significant factor associated with sensitivity to FxOH. CLIC4 regulates many cancer-related signals and participates in growth inhibition in FxOH-treated DLD-1 cells. Both CLIC4 knockdown and overexpression attenuated the inhibitory effects of FxOH on DLD-1 cells. Conclusion: Our findings suggest that the protein expression of CLIC4 and its regulating mechanisms play significant roles regarding cell death in human CRC cells by FxOH treatment. Further investigation by in vitro and in vivo models is needed to determine the effect of CLIC4.Colorectal cancer (CRC) is one of most prevalent cancers, with the third highest number of new cases (1.9 million per a total of 19.3 million) and second highest number of new deaths (0.9 million per a total of 10.0 million) worldwide, as estimated using the Global Cancer Observatory: CANCER TODAY 2020 database (1). The global incidence and mortality rates of CRC are expected to increase to more than 2.2 million new cases and 1.1 million deaths, respectively, by 2030 (2).Point mutations in certain driver genes, such as adenomatous polyposis coli, Kirsten-ras (KRAS) and tumor protein p53 (Tp53), and aberrant regulations of many other genes and processes, such as signal transduction, tumor microenvironment formation, immune suppression, and gut microbiota alteration, are considered to contribute to carcinogenesis and disease progression (3-14).The chloride intracellular channel (CLIC) protein family is a group of small globular proteins (28 kDa) comprising seven members: CLIC1, CLIC2, CLIC3, CLIC4, CLIC5A, CLIC5B, and CLIC6. They are ubiquitously expressed in various tissues and involved in intracellular trafficking, membrane remodeling, and other homeostatic mechanisms (15). Among these, CLIC4 has been well-studied for its association with cancer development. CLIC4 is a key molecule for apoptosis, angiogenesis, cell adhesion, wound healing, and tumorigenesis (14-20). In addition, CLIC4 expression is regulated by KRAS and Tp53 (21,22). We recently revealed that the number of CLIC4 high-expressing cells tended to decrease with the progression of pathological grades in colorectal malignant tissues of patients with CRC (23). These findings were also consistent with those of a previous study (24). Moreover, high expression levels of CLIC4 protein are suggested to be correlated with poor prognosis in patients with CRC and the aggressive pote...

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“…An important aspect of cancer genetics that these analyses miss is that potential interactions among SNPs may be associated with patient outcomes. For example, most of the studies in colorectal cancer have so far focused on individual SNPs' associations with outcome risk/survival times (10)(11)(12)(13)(14)(15)). However, it is possible that a SNP's genotypes may not be associated with the outcome on its own, but they may when they exist together with another SNP's genotypes (16).…”

Section: Introductionmentioning

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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A comprehensive analysis of SNPs and CNVs identifies novel markers associated with disease outcomes in colorectal cancer

Cited by 12 publications

References 101 publications

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol

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

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