Exploration of the carcinogenetic and immune role of CHK1 in human cancer

Abstract

Background: Previous study indicated that CHK1 was important for repairing DNA damage and cell cycle regulation. Aims: To investigate the association of Checkpoint kinase 1 (CHK1) expression with clinicopathological features, prognosis, and immune infiltration in cancer. Methods: Several databases were searched for relevant publications to conduct a meta-analysis to reveal the association between CHK1 and clinicopathological features of cancer. TIMER and GEPIA datasets were utilized to explore the differential expression of CHK1 of tumors. GEPIA and Kaplan-Meier Plotter databases were adopted to detect the prognostic significance of CHK1 in tumor. TIMER and cBioPortal databases were used for the analysis regarding immune infiltration and mutation respectively. Results: We found that CHK1 expression was significantly associated with low differentiation (OR=3.94, 95% CI: 2.73-5.67, P<0.05), advanced stage (OR=3.20, 95% CI: 2.30-4.44, P<0.05), vascular infiltration (OR=3.24, 95% CI: 2.18-4.82, P<0.05) and lymph node metastasis (OR=3.55, 95% CI: 2.62-4.82, P<0.05) of various cancers. CHK1 was highly expressed in multiple cancers and was related to clinical stage, survival, immune infiltration in pan-cancers. Conclusions: Our study found that CHK1 was significantly related to prognosis and immunological status in various cancers, suggesting that CHK1 may serve as a useful biomarker for prognosis and immune infiltration in cancer.

Keywords: CHK1; Clinicopathological features; Immune infiltration.; Pan-cancer; Prognosis.

Figure 1

The flow chart of article selection.

Figure 2

Association between CHK1 and clinicopathological feature in various cancers. (A-C) Forest plot, sensitivity analysis and funnel plot for association between CHK1 and cancer differentiation. (D-F) Forest plot, sensitivity analysis and funnel plot for association between CHK1 and cancer clinical stage. (G-I) Forest plot, sensitivity analysis and funnel plot for association between CHK1 and cancer vascular infiltration. (J-L) Forest plot, sensitivity analysis and funnel plot for association between CHK1 and cancer lymph node metastasis.

Figure 3

The expression of CHK1 in human cancers and clinicopathological stages. (A) Data from ONCOMINE database. Red cells: gene overexpression. Blue cells: decreased gene expression. Numbers: evidential frequencies. (B) CHK1 expression status in multiple tumors detect using TIMER dataset. ^**P < 0.01; ^***P <0.001. (C) Differential expression of CHK1 in TCGA project. ^*P <0.05. (D) Differential expression of CHK1 protein in CPTAC dataset. ^*** P < 0.001. (E) Correlation between CHK1 and clinical stages.

Figure 4

Association between CHK1 and clinical outcome of cancers in TCGA. (A) Overall survival, (B) Disease-free survival.

Figure 5

The prognostic significance of CHK1 in cancer patients. (A) Overall survival, (B) Relapse-free survival.

Figure 6

Mutation patterns of CHK1 in different cancer of TCGA. (A) Mutation type, (B) Mutation site, (C) The 3D structure of mutation site with the highest alteration frequency, (D) Association between mutation status and overall survival, disease-specific survival, disease-free survival, and progression-free survival in UCEC.

Figure 7

Enrichment analysis of CHK1 interacted or associated genes. (A) Experimentally determined interacted genes of CHK1. (B) Top 5 CHK1 associated genes in TCGA projects. (C) The corresponding heatmap map for correlation between CHK1 and top 5 related genes in various cancers. (D) An intersection analysis of CHK1 interacted and associated genes. (E) KEGG pathway analysis of CHK1 interacted or associated genes. (F) GO analysis of CHK1 interacted or associated genes.