Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

Yuan, Yihang; Chen, Ji; Wang, Jue; Xu, Ming; Zhang, Yunpeng; Sun, Peng; Liang, Leilei

doi:10.3389/fonc.2020.00638

Cited by 40 publications

(31 citation statements)

References 34 publications

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“…Among the other genes with strong evidence of association from the BRI method, EPHA7, TTC28, EVI2B, GPC3, CENPQ, NOTCH3, and SMPDL3A were previously reported to play a role in the development and prognosis of colorectal cancer (39)(40)(41)(42)(43)(44)(45). Our study is the first to report an association of C6orf120, COL22A1, FSIP1, AKR1D1, and CEP43 specifically with colorectal cancer risk.…”

Section: Discussionsupporting

confidence: 51%

Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer

Matejcic

Shaban

Quintana

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Inherited susceptibility is an important contributor to colorectal cancer risk, and rare variants in key genes or pathways could account in part for the missing proportion of colorectal cancer heritability.Methods: We conducted an exome-wide association study including 2,327 cases and 2,966 controls of European ancestry from three large epidemiologic studies. Single variant associations were tested using logistic regression models, adjusting for appropriate study-specific covariates. In addition, we examined the aggregate effects of rare coding variation at the gene and pathway levels using Bayesian model uncertainty techniques.Results: In an exome-wide gene-level analysis, we identified ST6GALNAC2 as the top associated gene based on the Bayesian risk index (BRI) method [summary Bayes factor (BF) BRI ¼ 2604.23]. A rare coding variant in this gene, rs139401613, was the top associated variant (P ¼ 1.01 Â 10 -6 ) in an exome-wide single variant analysis. Pathway-level association analyses based on the integrative BRI (iBRI) method found extreme evidence of association with the DNA repair pathway (BF iBRI ¼ 17852.4), specifically with the nonhomologous end joining (BF iBRI ¼ 437.95) and nucleotide excision repair (BF iBRI ¼ 36.96) subpathways. The iBRI method also identified RPA2, PRKDC, ERCC5, and ERCC8 as the top associated DNA repair genes (summary BF iBRI ≥ 10), with rs28988897, rs8178232, rs141369732, and rs201642761 being the most likely associated variants in these genes, respectively.Conclusions: We identified novel variants and genes associated with colorectal cancer risk and provided additional evidence for a role of DNA repair in colorectal cancer tumorigenesis.Impact: This study provides new insights into the genetic predisposition to colorectal cancer, which has potential for translation into improved risk prediction.

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Section: Discussionsupporting

confidence: 51%

Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer

Matejcic

Shaban

Quintana

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…It has been found that low expression of EVI2B could enhance cell proliferation, invasion and migration in colorectal cancer cells and remarkably promote tumor growth. besides, EVI2B participated in PPIs (protein-protein interactions) of T-cell-mediated system-wide modulation (29). Similarly, EVI2B was a potential prognostic biomarker for colorectal cancer (CRC) (30).…”

Section: Discussionmentioning

confidence: 99%

Identification and Verification of Immune-Related Gene Prognostic Signature Based on ssGSEA for Osteosarcoma

et al. 2020

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Osteosarcoma is the most common malignant bone tumor in children and adolescence. Multiple immune-related genes have been reported in different cancers. The aim is to identify an immune-related gene signature for the prospective evaluation of prognosis for osteosarcoma patients. In this study, we evaluated the infiltration of immune cells in 101 osteosarcoma patients downloaded from TARGET using the ssGSEA to the RNA-sequencing of these patients, thus, high immune cell infiltration cluster, middle immune cell infiltration cluster and low immune cell infiltration cluster were generated. On the foundation of high immune cell infiltration cluster vs. low immune cell infiltration cluster and normal vs. osteosarcoma, we found 108 common differentially expressed genes which were sequentially submitted to univariate Cox and LASSO regression analysis. Furthermore, GSEA indicated some pathways with notable enrichment in the high- and low-immune cell infiltration cluster that may be helpful in understanding the potential mechanisms. Finally, we identified seven immune-related genes as prognostic signature for osteosarcoma. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that the seven immune-related genes signature was an innovative and significant prognostic factor independent of clinical features. These results of this study offer a means to predict the prognosis and survival of osteosarcoma patients with uncovered seven-gene signature as potential biomarkers.

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“… 51 Moreover, it has been reported that CD48 can suppress CRC progression by inhibiting the proliferation, migration, and invasion capacity of CRC cells as well as tumour growth in vivo. 52 In the present study, we mainly focused on the expression pattern of ICGs and clinical correlation in CRC, so we included these ICGs as the object. Kaplan–Meier's survival analysis confirmed that the low expression groups of IDO1, CD274, CTLA4 and CD48 had the best prognosis, while the high expression groups of IDO1, CD274, CTLA4 and CD48 had the worst prognosis.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis and in vitro Experiments of Signatures and Prognostic Value of Immune Checkpoint Genes in Colorectal Cancer

Ma¹,

Qu²,

Che³

et al. 2021

OTT

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Purpose Immune checkpoints, as pivotal regulators of immune escape in cancer, can motivate the emergence of immune checkpoint inhibitors (ICIs). The aim of this study is to identify the expression of the immune checkpoint genes (ICGs) in colorectal cancer (CRC) and to relate their individual as well as combined expression to prognosis and therapeutic effectiveness in CRC. Methods RNA expression of 47 ICGs and clinical information of CRC patients were collected from two public databases to elucidate the expression levels and prognostic values of these ICGs in CRC. Then, the Shapiro–Wilk normality test was used to determine the normality of variables. Overall survival (OS) rates of each subset were found by Kaplan–Meier method, and the statistical significance was determined by the Log rank test ( p < 0.05). Results The expression of 13 and 9 ICGs was significantly associated with CRC prognosis in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. A series of ICGs was found to be significantly associated with TMB, neoantigens and MMR in CRC indicating that the combination of immunotherapy treatment biomarkers and ICGs may achieve accurate prognostic stratification of CRC, and potentially identify CRC cases that might respond to checkpoint inhibitors (CPIs). The subsets of high or low PD1/PD-L1/IDO1 expression stratified by CD48 were accurately associated with prognosis in CRC. In addition, in vitro experiments confirmed that VTCN1(B7-H4)-KD increases anti-PD-L1-mediated NK cell cytotoxicity on CRC tumor cells. Conclusion Although the expression of a single immune-checkpoint molecule does not predict the efficacy of immunotherapy in CRC, our findings infer that subsets defined by ICGs are associated with prognosis and imply the possibility that VTCN1 and CD48 serve as new immunotherapeutic targets.

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Identification Hub Genes in Colorectal Cancer by Integrating Weighted Gene Co-Expression Network Analysis and Clinical Validation in vivo and vitro

Cited by 40 publications

References 34 publications

Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer

Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer

Identification and Verification of Immune-Related Gene Prognostic Signature Based on ssGSEA for Osteosarcoma

Comparative Analysis and in vitro Experiments of Signatures and Prognostic Value of Immune Checkpoint Genes in Colorectal Cancer

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