Fig 1: CENPM modulates a biological network including nine genes associated with the cell cycle in breast cancer. Genes determined to be associated with CENPM by Spearman's rank correlation coefficient analysis (Spearman>0.4, P<0.001) of data from the cBioPortal database were selected to (A) draw a network, and (B) nine genes strongly correlated with CENPM were included in the network on the basis of their degrees of connectivity. Data on (C) CKS2 and (D) SHCBP1 mRNA expression in BRCA at different stages were downloaded from the Gene Expression Profiling Interactive Analysis database. CENPM, centromere protein M; BRCA, invasive breast carcinoma.
Fig 2: Working model for E2F1/CKS2/PTEN signaling axis in regulating malignant phenotypes of RB.CKS2 exhibits aberrant higher expression in retinoblastoma compared with normal controls. Upregulated transcription factor E2F1 bound to upstream of CKS2 transcription start site and promoted CKS2 protein production, leading to cancer-associated phenotypes, possibly by regulating PI3K–AKT signaling pathway.
Fig 3: Elevated CKS2 levels are associated with poor survival in patients with ccRCC. (A) Kaplan-Meier curves of the survival probability showing an improved overall survival for patients with low CKS2 expression levels compared with high CKS2 levels. Significance was assessed with log-rank test. Number at risk indicates the number of patients which are still alive at given time point; n=247. (B) Kaplan-Meier curves followed by log-rank test showing no significant difference in overall survival for patients with high PARK2 expression levels compared with low PARK2 levels; n=250. (C) Cox proportional hazard ratio showing an association between survival and different parameters, such as CKS2 expression, PARK2 expression, tumor grade and pT. *P<0.05, ***P<0.001 (D) Pearson's correlation analysis depicts a relationship between PARK2 and pT. In addition, CKS2 and pT were also analyzed. Bold values indicate significant p-values. (E) Spearman's correlation of CKS2 and grading as well as PARK2 and grading are depicted. (F) Pearson's correlation between CKS2 and PARK2 including Pearson's r, P-value, 95% CI, t-stat and df. ccRCC, clear cell renal cell carcinoma; CI, confidence interval; CKS2, CDC28 protein kinase regulatory subunit 2; df, degrees of freedom; PARK2, parkin; pT, pathologic tumor stage; t-stat, t-statistic.
Fig 4: Elevated expression of CKS2 predicts poor prognosis in patients with ULMS. Representative images of CKS2 staining by immunohistochemistry, demonstrating (A) low expression and (B) high expression of CKS2 in ULM tissues; and (C) low expression and (D) high expression of CKS2 in ULMS tissues. Magnification, ×400; scale bar, 20 µm. (E) Kaplan-Meier survival curves of patients with ULMS according to the levels of CKS2 expression. CKS2, cyclin-dependent kinase subunit 2; ULMS, uterine leiomyosarcoma; ULM, uterine leiomyoma.
Fig 5: Representative images of the grading system used in the tissue microarray analysis. (A-E) Different staining intensities of PARK2 in (A) non-malignant and (B-E) ccRCC tissue are shown; (B) negative, (C) weakly positive, (D) moderately positive, (E) strongly positive. (F-I) Different staining intensities of CKS2 in (F) non-malignant (G-I) and ccRCC tissue (G) weakly positive, (H) moderately positive, (I) strongly positive.
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