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. 2021 Dec 14;13(23):25466-25483.
doi: 10.18632/aging.203767. Epub 2021 Dec 14.

Prognostic value of CDCA3 in kidney renal papillary cell carcinoma

Hao Li  1 , Mi Li  1 , Caihong Yang  1 , Fengjing Guo  1 , Sisi Deng  2 , Lixi Li  3 , Tian Ma  1 , Jiyuan Yan  1 , Hua Wu  1 , Xiaojuan Li  3
Affiliations

Prognostic value of CDCA3 in kidney renal papillary cell carcinoma

Hao Li et al. Aging (Albany NY). .

Abstract

Kidney renal papillary cell carcinoma (KIRP) is a type of low-grade malignant renal cell carcinoma. Huge challenges remain in the treatment of KIRP. Cell division cycle associated 3 (CDCA3) participates in human physiological and pathological processes. However, its role in KIRP has not been established. Here, we evaluated the prognostic value of CDCA3 in KIRP using a comprehensive bioinformatics approach. Data for CDCA3 expression in KIRP were obtained from online database. Different expression genes between high and low CDCA3 expression groups were identified and evaluated by performing Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A gene set enrichment analysis was performed to elucidate the function and pathway differences between the different. Differences in immune cell infiltration between low and high CDCA3 expression groups were analyzed by a single-sample GSEA method for immune cells. A protein-protein interaction network was generated and hub genes were identified. UALCAN was used to analyze associations between the mRNA expression levels of CDCA3 in KIRP tissues with clinicopathologic parameters. The diagnostic efficacy of CDCA3 for KIRP was analyzed by ROC analysis. Logistic regression was used to analyze relationships between the clinicopathological characteristics and CDCA3 expression. Our results indicated that high CDCA3 mRNA expression is significantly associated with some clinicopathologic parameters in KIRP patients High CDCA3 mRNA expression associated with a shorter overall survival, progression-free interval, and disease-special survival. Taken together, CDCA3 is a potential target for the development of anti-KIRP therapeutics and is an efficient prognostic marker.

Keywords: cell division cycle associated 3; differential expression; immune cell infiltration; kidney renal papillary cell carcinoma; prognostic values.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overexpression of CDCA3 in patients with KIRP. (A) CDCA3 expression in normal samples from the GTEx database and the TCGA and 33 tumor samples in TCGA. ns, p ≥ 0.05; *, p < 0.05; **, p< 0.01; ***, p < 0.001. (B) CDCA3 expression in 33 tumor samples in TCGA and paired paracancerous tissues in TCGA. ns, p ≥ 0.05; *, p < 0.05; **, p < 0.01; ***, p < 0.001. (C) CDCA3 mRNA expression level in 288 KIRP samples and 32 normal samples. *** p < 0.001. (D) CDCA3 mRNA expression in KIRP tissues and in paired paracancerous normal samples. *** p < 0.001. (E) CDCA3 mRNA expression in normal samples and KIRP from the GTEx database and TCGA. *** p < 0.001.
Figure 2
Figure 2
DEGs associated with CDCA3 in KIRP. (A) The results of the DEGs analysis with a volcano graph. |logFC| > 1.5 and padj < 0.05. (B) The results of the most distinctly DEGs with a heat map.
Figure 3
Figure 3
GO and KEGG pathway enrichment analyses. (A–C) GO enrichment analyses of DEGs associated with CDCA3. (A) Cellular component; (B) Biological processes; (C) Molecular functions (D) KEGG enrichment analyses of DEGs associated with CDCA3.
Figure 4
Figure 4
CDCA3-related signaling pathways based on GSEA. (A–D) Typical results of the GSEA for a single gene set. NES, normalized ES; p.adj, adjust p value; FDR, false discovery rate.
Figure 5
Figure 5
Immune cell infiltration. (A–Y) Spearman correlation analyses of the associations between the CDCA3 expression and the infiltration of 24 types of immune cells.
Figure 6
Figure 6
PPI network construction. (A) A PPI network was constructed using Cytoscape. (B) The most significant module was using MCODE of Cytoscape.
Figure 7
Figure 7
Clinicopathological factors associated with CDCA3 in KIRP. (A–L) CDCA3 mRNA expression with clinicopathological parameters of patients with KIRP, including clinical stage, gender, race, age, smoking status, serum calcium, hemoglobin, laterality and MET status. ns, p ≥ 0.05; *, p < 0.05; **, p < 0.01; ***, p < 0.001.
Figure 8
Figure 8
ROC analysis. (A, B) the diagnostic efficacy of CDCA3 for KIRP both the TCGA database and the TCGA combined with the GTEX database.
Figure 9
Figure 9
Survival analyses. (A–C)The prognostic value of CDCA3 with OS, PFI, DSS. (D–F) The nomogram of CDCA3 with OS, PFI, DSS. (G–I) The calibration curve of N stage (green), M stage (blue) and CDCA3 (red) with OS, PFI, DSS.
Figure 10
Figure 10
Survival analysis of subgroups. (A–C) Prognostic value of CDCA3 with OS, PFI, DSS of KIRP subgroup.
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