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. 2020 Mar;19(3):1815-1823.
doi: 10.3892/ol.2020.11254. Epub 2020 Jan 7.

High Expression of Citron Kinase Predicts Poor Prognosis of Prostate Cancer

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Free PMC article

High Expression of Citron Kinase Predicts Poor Prognosis of Prostate Cancer

Junnan Liu et al. Oncol Lett. .
Free PMC article

Abstract

Citron kinase (CIT) is a Rho-effector protein kinase that is associated with several types of cancer. However, the role of CIT in prostate cancer (PCa) is unclear. The current study utilized microarray data obtained from The Cancer Genome Atlas, which was analyzed via Biometric Research Program array tools. Additionally, reverse transcription-quantitative (RT-q)PCR was performed to compare the mRNA expression of CIT in PCa tissue and in benign prostatic hyperplasia. The protein expression of CIT was detected in a consecutive cohort via immunochemistry and CIT was screened as a potential oncogene in PCa. The results of RT-qPCR demonstrated that the mRNA expression of CIT was increased in PCa tissues. Furthermore, immunochemistry revealed that CIT protein expression was positively associated with age at diagnosis, Gleason grade, serum PSA, clinical T stage, risk group, lymph node invasion and metastasis. When compared with the low expression group, patients with a high CIT expression exhibited shorter survival rates, cancer specific mortalities (CSM) and biochemical recurrence (BCR). In addition, multivariate analysis revealed that CIT was a potential predictor of CSM and BCR. The results revealed that CIT is overexpressed during the malignant progression of PCa and may be a predictor of a poor patient prognosis.

Keywords: citron kinase; prognosis; prostate cancer.

Figures

Figure 1.
Figure 1.
CIT is screened as a PCa-associated gene from the TCGA database. The fold-changes (log2 scale) of gene expression between different parameters were plotted on the y-axis and the P-values (log2 scale) of the FDR-corrected t-test were plotted on the x-axis. The screening of DEGs was based on the TCGA cohort (PRAD_2015_02_24) and is indicated by blue dots (P<0.01). CIT is indicated by red dots (P<0.01). CIT, citron kinase; PCa, prostate cancer; TCGA, The Cancer Genome Atlas; DEGs, differentially expressed genes; FDR, false discovery rate; PSA, prostate specific antigen.
Figure 2.
Figure 2.
CIT expression is increased in PCa. (A) CIT mRNA was extracted from 35 cases of fresh PCa and 20 cases of BPH. The results of reverse transcription-quantitative PCR revealed that the mRNA expression of CIT was increased in PCa samples. Data are presented as the SEM. The overall comparison between PCa and BPH is presented in the box plot with the median result, in which the bottom and top of the boxes represent the maximum and minimum value, respectively. (B) The slides for IHC were cut from formalin fixed paraffin embedded tissue obtained from 39 cases of BPH and 271 cases of PCa. Representative images of IHC indicate CIT staining. No staining was present in BPH tissue; light staining was exhibited in low-grade PCa, moderate staining was revealed in middle-grade PCa and strong staining was indicated in high-grade PCa. Each image was captured at a respective magnification of ×200 and ×400, respectively. Compared with BPH, there was a significant increase in primary and aggressive PCa, whereas no statistically significant difference was observed between primary and aggressive PCa (C) The expression of CIT in HR-group was also higher than nonHR-group (D). Error bars represent the SEM. The data in A and D were analyzed using an unpaired t-test, and the data in C were analyzed using Kruskal-Wallis test ***P<0.001. CIT, citron kinase; PCa, prostate cancer; BPH, benign prostatic hyperplasia; IHC, immunohistochemistry; SEM, standard error of the mean; HR, high risk.
Figure 3.
Figure 3.
Prognostic value of CIT in PCa. (A and C) As revealed by the results of immunohistochemistry, the protein level of CIT was increased in BCR and CSM patients. Error bars represent the standard error of the mean. ***P<0.001. (B and D) Kaplan-Meier survival analysis revealed the survival time of BCR and CSM patients, with a high or low CIT expression. Data were analyzed using a log-rank test. CIT, citron kinase; PCa, prostate cancer; BCR, biochemical recurrence; CSM, cancer specific mortality.

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