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. 2022 Jun 21:2022:1893351.
doi: 10.1155/2022/1893351. eCollection 2022.

Identification of Hub Genes for Early Diagnosis and Predicting Prognosis in Colon Adenocarcinoma

Shuo Xu  1 , Dingsheng Liu  1 , Mingming Cui  1 , Yao Zhang  1 , Yu Zhang  1 , Shiqi Guo  1 , Hong Zhang  1
Affiliations

Identification of Hub Genes for Early Diagnosis and Predicting Prognosis in Colon Adenocarcinoma

Shuo Xu et al. Biomed Res Int. .

Retraction in

Abstract

Colon adenocarcinoma (COAD) is among the most common digestive system malignancies worldwide, and its pathogenesis and gene signatures remain unclear. This study explored the genetic characteristics and molecular mechanisms underlying colon cancer development. Three gene expression data sets were obtained from the Gene Expression Omnibus (GEO) database. GEO2R was used to determine differentially expressed genes (DEGs) between COAD and normal tissues. Then, the intersection of the data sets was obtained. Metascape was used to perform the functional enrichment analyses. Next, STRING was used to build protein-protein interaction (PPI) networks. Hub genes were identified and analysed using Cytoscape. Next, survival analysis and expression analysis of the hub genes were performed. ROC curve analysis was performed for further test of the diagnostic efficacy. Finally, alterations in the hub genes were predicted and analysed by cBioPortal. Altogether, 436 DEGs were detected. The DEGs were mainly enriched in cell cycle phase transition, nuclear division, meiotic nuclear division, and cytokinesis. Based on PPI networks, 20 hub genes were selected. Among them, 6 hub genes (CCNB1, CCNA2, AURKA, NCAPG, DLGAP5, and CENPE) showed significant prognostic value in colon cancer (P < 0.05), while 5 hub genes (CDK1, CCNB1, CCNA2, MAD2L1, and DLGAP5) were associated with early colon cancer diagnosis and ROC curve analysis showed good diagnostic accuracy. In conclusion, integrated bioinformatics analysis was used to identify hub genes that reveal the potential mechanism of carcinogenesis and progression of colon cancer. The hub genes might be novel biomarkers for early diagnosis, treatment, and prognosis of colon cancer.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Venn diagram of DEGs from three datasets. (a) 267 downregulated DEGs. (b) 169 upregulated DEGs. Abbreviations: DEGs: differentially expressed genes.
Figure 2
Figure 2
DEG and neighbouring gene enrichment analysis in COAD using Metascape. (a) Heatmap of GO enriched terms coloured by P value. (b) Network of GO enriched terms coloured by P value. Each node represents an enriched term. Dark colours indicate increased statistical significance. (c) Heatmap of KEGG and Reactome enriched terms coloured by P value. (d) Network of KEGG and Reactome enriched terms coloured by P value. Each node represents an enriched term. Darker colour indicates more statistical significance. Abbreviations: DEGs: differentially expressed genes; COAD: colon adenocarcinoma; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 3
Figure 3
PPI network of DEGs, containing 369 nodes and 2708 edges. Red represents upregulated genes. Blue represents downregulated genes. Abbreviations: PPI: protein-protein interaction; DEGs: differentially expressed genes.
Figure 4
Figure 4
The most significant module gene network and hub genes analysis. (a) The most significant module in the PPI network contains 62 nodes and 1708 edges. (b) Network of 20 hub genes. Darker colours represent higher scores. (c) Biological process annotation of hub genes using ClueGO and CluePedia. P < 0.01 was considered statistically significant. (d) KEGG annotation of hub genes using ClueGO and CluePedia. P < 0.01 was considered statistically significant. (e) Heatmap of the top 20 hub genes was constructed using the UALCAN database. Abbreviations: PPI: protein-protein interaction; KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 5
Figure 5
Overall survival of the hub genes in COAD patients. (a)–(f) CCNB1, CCNA2, AURKA, NCAPG, DLGAP5, and CENPE showed a significant difference in overall survival (OS). High expression of the 6 genes indicated favourable OS in COAD (P < 0.05). (g, h) AURKA and CENPE showed statistically significant association with disease-free survival (DFS) and indicated favourable disease-free survival in COAD (P < 0.05). Abbreviations: COAD: colon adenocarcinoma.
Figure 6
Figure 6
Differential expression analysis of the 5 hub genes was performed by UALCAN. (a, d, g, j, and m) mRNA expression of the five genes was overexpressed in colon cancer compared to normal colon tissues. (b, e, h, k, and n) mRNA expression of the five genes was significantly related to individual cancer stage, with the highest expressions tending to appear at stage 1. (c, f, i, l, and o) mRNA expression of the five genes was significantly related to nodal metastasis status, and the highest mRNA expression tended to appear at the N0 phase. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
Figure 7
Figure 7
Protein expression analysis of the 5 hub genes was performed using the HPA database. Except for MAD2L1, the other 4 proteins showed a higher degree of staining in tumour tissue compared to normal tissues.
Figure 8
Figure 8
ROC curves analysis of the five hub genes, CDK1, CCNB1, CCNA2, MAD2L1, and DLGAP5. AUCs were used to assess the five hub genes, and the results showed high diagnostic accuracy.
Figure 9
Figure 9
Alterations of the eight hub genes analysed by cBioPortal. (a) OncoPrint of genetic alterations in 378 COAD cases. (b) Alteration frequency of eight hub genes. Gene expression was altered in 42.86% of 378 cases. Abbreviations: COAD: colon adenocarcinoma.
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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R. L., Torre L. A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians . 2018;68(6):394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Arnold M., Sierra M. S., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut . 2017;66(4):683–691. doi: 10.1136/gutjnl-2015-310912. - DOI - PubMed
    1. Miller K. D., Nogueira L., Mariotto A. B., et al. Cancer treatment and survivorship statistics, 2019. CA: a Cancer Journal for Clinicians . 2019;69(5):363–385. doi: 10.3322/caac.21565. - DOI - PubMed
    1. Issa I. A., Noureddine M. Colorectal cancer screening: an updated review of the available options. World Journal of Gastroenterology . 2017;23(28):5086–5096. doi: 10.3748/wjg.v23.i28.5086. - DOI - PMC - PubMed
    1. Kim Y. S., Kim N., Kim S. H., et al. The efficacy of intravenous contrast-enhanced 16-raw multidetector CT colonography for detecting patients with colorectal polyps in an asymptomatic population in Korea. Journal of Clinical Gastroenterology . 2008;42(7):791–798. doi: 10.1097/MCG.0b013e31811edcb7. - DOI - PubMed

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