Clinical significance and biological roles of cyclins in gastric cancer

Abstract

Background and aim: Cyclins have been reported to be overexpressed with poor prognosis in several human cancers. However, limited numbers of studies evaluated the expressions and prognostic roles of cyclins in gastric cancer (GC). We aim to evaluate the expressions and prognostic roles of cyclins. Also, further efforts were made to explore biological function of the differentially expressed cyclins.

Methods: Cyclins expressions were analyzed by Oncomine and The Cancer Genome Atlas datasets, and the prognostic roles of cyclins in GC patients were investigated by the Kaplan-Meier Plotter database. Then, a comprehensive PubMed literature search was performed to identify expression and prognosis of cyclins in GC. Biological functions of the differentially expressed cyclins were explored through Enrich R platform, and KEGG and transcription factor were analyzed.

Results: The expression levels of CCNA2 (cyclin A2), CCNB1 (cyclin B1), CCNB2 (cyclin B2), and CCNE1 (cyclin E1) mRNAs were identified to be significantly higher in GC tissues than in normal tissues in both Oncomine and The Cancer Genome Atlas datasets. High expressions of CCNA2, CCNB1, and CCNB2 mRNAs were identified to be related with poor overall survival in Kaplan-Meier Plotter dataset. Evidence from clinical studies showed that CCNB1 was related with overall survival in GC patients. Cyclins were associated with several biological pathways, including cell cycle, p53 signaling pathway, FoxO signaling pathway, viral carcinogenesis, and AMPK signaling pathway. Enrichment analysis also showed that cyclins interacted with some certain transcription factors, such as FOXM1, SIN3A, NFYA, and E2F4.

Conclusion: Based on our results, high expressions of cyclins were related with poor prognosis in GC patients. The above information might be useful for better understanding the clinical and biological roles of cyclins mRNA and guiding individualized treatments for GC patients.

Keywords: biological function; cyclins; expression; gastric cancer; prognosis.

Figure 1

Cyclins expression in gastric cancer in Oncomine datasets. Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, (D) CCND2, and (E) CCNE1. Data were analyzed in Oncomine datasets by comparative meta-analysis. Abbreviations: GC, gastric cancer; std, standard.

Figure 2

Cyclins expression in GC in TCGA dataset. Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, (D) CCND2, and (E) CCNE1. Data were analyzed in TCGA dataset. ^***P<0.001. Abbreviations: GC, gastric cancer; TCGA, The Cancer Genome Atlas.

Figure 3

CCNB1 and CCNE1 expressions in GC Lauren subtype. Notes: (A) CCNB1 expression in diffuse gastric adenocarcinoma. (B) CCNB1 expression in gastric intestinal type adenocarcinoma. (C) CCNE1 expression in diffuse gastric adenocarcinoma. (D) CCNE1 expression in gastric intestinal type adenocarcinoma. Data were analyzed in TCGA dataset. ^***P<0.001. Abbreviations: GC, gastric cancer; TCGA, The Cancer Genome Atlas.

Figure 4

Prognosis roles of differentially expressed cyclins in GC patients in KM Plotter datasets. Notes: (A) CCNA2, (B) CCNB1, (C) CCNB2, and (D) CCNE1. Data were analyzed in KM Plotter datasets. Abbreviations: GC, gastric cancer; KM Plotter, Kaplan–Meier Plotter.

Figure 5

Prognosis roles of CCNB1 in different GC patients. Notes: (A) Prognostic role of CCNE1 in GC patients who received 5-FU-based chemotherapy treatment. (B) Prognostic role of CCNE1 in GC HER2-negative patients. Data were analyzed in KM Plotter datasets. Abbreviations: GC, gastric cancer; KM Plotter, Kaplan–Meier Plotter.

Figure 6

Protein–protein interaction network of differentially expressed cyclins.