High nuclear/cytoplasmic ratio of Cdk1 expression predicts poor prognosis in colorectal cancer patients

Sung, Wen‐Wei; Lin, Yueh‐Min; Wu, Pei‐Wen; Yen, Hsu‐Heng; Lai, Hung-Wen; Su, Tzu-Cheng; Huang, Ren-Hung; Wen, Chun-Kai; Chen, Chia-Yu; Chen, Chih‐Jung; Yeh, Kun‐Tu

doi:10.1186/1471-2407-14-951

Cited by 113 publications

(101 citation statements)

References 22 publications

(39 reference statements)

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“…Also, no differences were shown within the LSCC samples group when the N0 group was compared to N+ group. This is in contrast to findings from colorectal tumor when it has been shown that high nuclear/cytoplasmic ratio of CDK1 expression is connected with poor prognosis in this type of cancer [48]. …”

Section: Discussioncontrasting

confidence: 90%

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

et al. 2016

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In this study, we analyzed the expression profile of four genes (CCNA2, CCNB1, CCNB2, and CDK1) in laryngeal squamous cell carcinoma (LSCC) cell lines and tumor samples. With the application of microarray platform, we have shown the overexpression of these genes in all analyzed LSCC samples in comparison to non-cancer controls from head and neck region. We have selected CDK1 for further analysis, due to its leading role in cell cycle regulation. It is a member of the Ser/Thr protein kinase family of proven oncogenic properties. The results obtained for CDK1 were further confirmed with the application of reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique, Western blot, and immunohistochemistry (IHC). The observed upregulation of CDK1 in laryngeal squamous cell carcinoma has encouraged us to analyze for genetic mechanisms that can be responsible this phenomenon. Therefore, with the application of array-CGH, sequencing analysis and two methods for epigenetic regulation analysis (DNA methylation and miRNA expression), we tried to identify such potential mechanisms. Our attempts to identify the molecular mechanisms responsible for observed changes failed as we did not observe significant alterations neither in the DNA sequence nor in the gene copy number that could underline CDK1 upregulation. Similarly, the pyrosequencing and miRNA expression analyses did not reveal any differences in methylation level and miRNA expression, respectively; thus, these mechanisms probably do not contribute to elevation of CDK1 expression in LSCC. However, our results suggest that alteration of CDK1 expression on both mRNA and protein level probably appears on the very early step of carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-4991-4) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 90%

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

et al. 2016

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“…It has been reported that Cdk1 expression or activity is elevated in Hodgkin's lymphomas [5], human colorectal cancer [6], prostate cancer [7], gastric lymphoma [8], childhood acute lymphoblastic leukemia [9] Therefore, Cdk1 is closely related with cancer progression. In particular, it has been reported that prognosis is poor in colorectal cancer patients with a high nuclear/cytoplasmic ratio of Cdk1 [6]. When activity of CDK1 and CDK2 was high in renal cell carcinoma patients, recurrence prediction rate was also high, while progression-free survival rate was low [10].…”

Section: Introductionmentioning

confidence: 99%

Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer

et al. 2016

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Cyclin dependent kinase 1 (Cdk1) have previously reported correlation with cancer growth and a key regulator for cell cycle. Mostly, Cdk1′s function of nucleus for cell cycle is well known to be associated with cancer, but cytoplasmic Cdk1′s traits are not clearly identified, yet. We revealed that tissue microarray blocks of epithelial ovarian cancer (n = 249) showed increased level of cytoplasmic Cdk1 (p < 0.001), but not in nucleus (p = 0.192) of histologic cell type independently. On survival analysis, Cdk1 overexpression conferred a significantly worse prognosis in 5-year overall survival (Log-rank p = 0.028, Hazard ratio = 2.016, 95% CI = 1.097 to 4.635). Also, the expression of Cdk1 was increased in ovarian cancer cell lines and Gene Expression Omnibus datasets. When the expression and activity of Cdk1 were inhibited by si-Cdk1 or RO-3306 which is a potent Cdk1 inhibitor, the growth of ovarian cancer was diminished. Moreover, combined treatment with RO-3306 and cisplatin in ovarian cancer significantly elevated anti-cancer effects than single-agent treatment. In conclusion, cytoplasmic Cdk1 expression which was elevated in ovarian cancer predicts a poor overall survival. The inhibition of Cdk1 expression and activity reduced ovarian cancer growth.

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“…4 ( SIRT1, TGFBR1, CDK1 , and SMAD1 ) of the 15 genes were not present in any of the multi-tumor type cancer studies. All of the latter 4 genes contain cancer-related evidence232425262728293031, with SIRT1 and TGFBR1 also having documented genomic alterations293031 (Supplementary Note). …”

Section: Resultsmentioning

confidence: 99%

Driver gene classification reveals a substantial overrepresentation of tumor suppressors among very large chromatin-regulating proteins

Waks

Weissbrod

Carmeli

et al. 2016

Sci Rep

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Compiling a comprehensive list of cancer driver genes is imperative for oncology diagnostics and drug development. While driver genes are typically discovered by analysis of tumor genomes, infrequently mutated driver genes often evade detection due to limited sample sizes. Here, we address sample size limitations by integrating tumor genomics data with a wide spectrum of gene-specific properties to search for rare drivers, functionally classify them, and detect features characteristic of driver genes. We show that our approach, CAnceR geNe similarity-based Annotator and Finder (CARNAF), enables detection of potentially novel drivers that eluded over a dozen pan-cancer/multi-tumor type studies. In particular, feature analysis reveals a highly concentrated pool of known and putative tumor suppressors among the <1% of genes that encode very large, chromatin-regulating proteins. Thus, our study highlights the need for deeper characterization of very large, epigenetic regulators in the context of cancer causality.

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High nuclear/cytoplasmic ratio of Cdk1 expression predicts poor prognosis in colorectal cancer patients

Cited by 113 publications

References 22 publications

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma

Accumulation of cytoplasmic Cdk1 is associated with cancer growth and survival rate in epithelial ovarian cancer

Driver gene classification reveals a substantial overrepresentation of tumor suppressors among very large chromatin-regulating proteins

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