The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review

Li, Kai; Zheng, Minying; Lu, Rui; Du, Jiaxing; Zhao, Qi; Li, Zugui; Li, Yuwei; Zhang, Shiwu

doi:10.1186/s12935-020-01304-w

Cited by 189 publications

(157 citation statements)

References 169 publications

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“…Cell Division Cycle 25C (CDC25C) plays an important role in the regulation of G2/M processes and mediates DNA damage repair by checkpoint protein regulation in case of DNA damage. The abnormal expression of cdc25c is related to tumorigenesis and development, and it is a promising therapeutic target ( Liu et al, 2020 ). A large number of mitochondrial DNA (mtDNA) deletion is related to many human diseases and aging.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Wang

et al. 2021

Front. Genet.

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Backgrounds: Colorectal cancer (CRC) with high incidence, has the third highest mortality of tumors. DNA damage and repair influence a variety of tumors. However, the role of these genes in colon cancer prognosis has been less systematically investigated. Here, we aim to establish a corresponding prognostic signature providing new therapeutic opportunities for CRC.Method: After related genes were collected from GSEA, univariate Cox regression was performed to evaluate each gene’s prognostic relevance through the TCGA-COAD dataset. Stepwise COX regression was used to establish a risk prediction model through the training sets randomly separated from the TCGA cohort and validated in the remaining testing sets and two GEO datasets (GSE17538 and GSE38832). A 12-DNA-damage-and-repair-related gene-based signature able to classify COAD patients into high and low-risk groups was developed. The predictive ability of the risk model or nomogram were evaluated by different bioinformatics‐ methods. Gene functional enrichment analysis was performed to analyze the co-expressed genes of the risk-based genes.Result: A 12-gene based prognostic signature established within 160 significant survival-related genes from DNA damage and repair related gene sets performed well with an AUC of ROC 0.80 for 5 years in the TCGA-CODA dataset. The signature includes CCNB3, ISY1, CDC25C, SMC1B, MC1R, LSP1P4, RIN2, TPM1, ELL3, POLG, CD36, and NEK4. Kaplan-Meier survival curves showed that the prognosis of the risk status owns more significant differences than T, M, N, and stage prognostic parameters. A nomogram was constructed by LASSO regression analysis with T, M, N, age, and risk as prognostic parameters. ROC curve, C-index, Calibration analysis, and Decision Curve Analysis showed the risk module and nomogram performed best in years 1, 3, and 5. KEGG, GO, and GSEA enrichment analyses suggest the risk involved in a variety of important biological processes and well-known cancer-related pathways. These differences may be the key factors affecting the final prognosis.Conclusion: The established gene signature for CRC prognosis provides a new molecular tool for clinical evaluation of prognosis, individualized diagnosis, and treatment. Therapies based on targeted DNA damage and repair mechanisms may formulate more sensitive and potential chemotherapy regimens, thereby expanding treatment options and potentially improving the clinical outcome of CRC patients.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Wang

et al. 2021

Front. Genet.

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“…Aberrant expression of proteins associated with the cell cycle can lead to tumor invasion, metastasis, induce drug resistance, and resist apoptosis. Many cell cycle-related proteins have become cancer therapeutic targets ( 31 ). Aurora-A belongs to the Aurora serine/threonine kinase family.…”

Section: Discussionmentioning

confidence: 99%

AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma

Kang

et al. 2020

Front. Oncol.

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AUNIP, a novel prognostic biomarker, has been shown to be associated with stromal and immune scores in oral squamous cell carcinoma (OSCC). Nonetheless, its role in other cancer types was unclear. In this study, AUNIP expression was increased in hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD) according to data from The Cancer Genome Atlas (TCGA) database, Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), and Gene Expression Omnibus (GEO) database (GSE45436, GSE102079, GSE10072, GSE31210, and GSE43458). Further, according to copy number variation analysis, AUNIP up-regulation may be associated with copy number variation. Immunohistochemistry showed AUNIP expression was higher in HCC and LUAD compared with the normal tissues. Receiver operating characteristic (ROC) curve analysis demonstrated that AUNIP is a candidate diagnostic biomarker for HCC and LUAD. Next, TCGA, International Cancer Genome Consortium (ICGC), and GEO (GSE31210 and GSE50081) data showed that increased AUNIP expression clearly predicted poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HCC and LUAD. Additionally, multivariate Cox regression analysis involving various clinical factors showed that AUNIP is an independent prognostic biomarker for HCC and LUAD. Next, the role of AUNIP in HCC and LUAD was explored via a co-expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and a gene set variation analysis (GSVA). HCC and LUAD exhibited almost identical enrichment results. More specifically, high AUNIP expression was associated with DNA replication, cell cycle, oocyte meiosis, homologous recombination, mismatch repair, the p53 signal transduction pathway, and progesterone-mediated oocyte maturation. Lastly, the Tumor Immune Estimation Resource (TIMER) tool was used to determine the correlations of AUNIP expression with tumor immune infiltration. AUNIP expression was positively correlated with the infiltration degree of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in HCC. However, AUNIP expression was negatively correlated with the infiltration degree of B cells, CD4+ T cells, and macrophages in LUAD. In addition, AUNIP expression was correlated with immune infiltration in various other tumors. In conclusion, AUNIP, which is associated with tumor immune infiltration, is a candidate diagnostic and prognostic biomarker for HCC and LUAD.

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“…Ninety-six, out of 554 genes with bimodal gene expression in all tumor types analyzed here, were identified as having differential prognosis when patients belonging to the two different modes were compared. Expression of several genes identified by us are known predictors of clinical outcome in different tumor types including ANXA1 [28], FOXJ3 [29,30] and CDC25 [31,32], among many others. However, the great majority of these reports only associate expression with prognosis.…”

Section: Discussionmentioning

confidence: 99%

A new genome-wide method to identify genes with bimodal gene expression

Justino

Reis²,

Fonseca³

et al. 2020

Preprint

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A new method is presented to detect bimodality in gene expression data using the Gaussian Mixture Models to cluster samples in each mode. We have used the method to search for bimodal genes in data from 25 tumor types available from The Cancer Genome Atlas. The method identified 554 genes with bimodal gene expression, of which 46 were identified in more than one cancer type. To further illustrate the impact of the method, we show that 96 out of the 554 genes with bimodal expression patterns presented different prognosis when patients belonging to the two expression peaks are compared. The software to execute the method and the corresponding documentation are available at https://github.com/LabBiosystemUFRN/Bimodality_Genes.

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The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review

Cited by 189 publications

References 169 publications

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma

A new genome-wide method to identify genes with bimodal gene expression

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