High expression of citron kinase predicts poor prognosis of prostate cancer

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.

Gene expression of cytokinesis regulators PRC1, KIF14 and CIT has no prognostic role in colorectal and pancreatic cancer

“…Prognostic significance of PRC1, KIF14 and CIT has been so far reported in lung, ovarian, breast, cervical, gastric, hepatocellular, bladder and prostate cancers ( 21 – 25 , 39 – 45 ), however, the present study demonstrated no prognostic significance of PRC1, KIF14 and CIT for CRC and PDAC.…”

“…PRC1, KIF14 and CIT transcript expression is dysregulated, mainly upregulated, in several malignancies, e.g., breast, hepatocellular, bladder, prostate and ovarian cancers ( 21 – 25 ) and therefore, the relevance of these cytokinesis regulators for tumor initiation and progression is being intensively studied currently ( 36 – 38 ). Transcript levels of all 3 genes strongly correlated together in the present study further demonstrating their importance for cancer progression and potential as potential therapeutic targets.…”

“…Besides a few rather small-scale experimental studies in various cancer types, e.g., breast ( 21 ), ovarian ( 22 , 40 ), cervical ( 41 ) and prostate ( 25 ) carcinomas, Big Data mining, from the Gene Expression Omnibus (GEO) or the Cancer Genome Atlas (TCGA) databases, using various in silico bioinformatics have demonstrated that some cytokinesis regulators may have prognostic value alone or as a part of a specific gene sets ( 50 – 52 ). For example, KIF14 is one of 10 genes whose low transcript expression in the GSE62452 microarray dataset, composed of 69 PDAC tumors predicted significantly poorer OS time of patients with PDAC and this was also observed in the TCGA RNASeq dataset ( 50 ).…”

“…In addition, patients with breast cancer with high PRC1 expression level in tumors had significantly worse disease-free survival time compared with the rest of patients (21), and low CIT level was associated with worse time to progression in patients with ovarian cancer (22). In fact, the prognostic role of these regulators of cytokinesis was recently suggested by others in hepatocellular, prostate and bladder cancer (23)(24)(25).…”

“…The present study aimed to assess the prognostic relevance of the cytokinesis regulators in PRC1, KIF14 and CIT in patients with CRC and PDAC. PRC1, KIF14 and CIT were selected based on previous functional evidence and putative prognostic roles reported in other carcinomas (21)(22)(23)(24)(25).…”