Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma

Karavias, Dimitrios; Maroulis, Ioannis; Papadaki, Helen; Gogos, Charalambos; Kakkos, Stavros K.; Karavias, Dionissios; Bravou, Vasiliki

doi:10.1007/s11605-015-2960-7

Cited by 37 publications

(37 citation statements)

References 34 publications

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“…Further studies are needed to fully elucidate the relationships between clinical behaviors and CDT1 or geminin expression. Although there were no apparent associations between γ‐H2A.X and prognostic factors, as described by Karavias et al, γ‐H2A.X expression tended to decrease in patients with advanced T and M stages in our study. These findings suggested that γ‐H2A.X may play a key role in OSCC progression.…”

Section: Discussioncontrasting

confidence: 52%

“…Additionally, slightly high CDT1 expression was correlated with OSCC recurrence and postoperative metastasis, although high CDT1 expression also tended to be associated with patient survival. In a previous study, overexpression of CDT1 was shown to be a predictor of poor survival in patients with hepatocellular carcinoma . Thus, the expression of CDT1 may depend on the tumor type and grade.…”

Section: Discussionmentioning

confidence: 88%

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Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

Siril

Kouketsu

Oikawa

et al. 2019

J Oral Pathology Medicine

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Background Carcinogenesis occurs when the cell cycle is compromised. Chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A histone family member X are expressed in cells in G1 phase, S/G2/M phases, and apoptosis, respectively, and these three markers may be useful for histological evaluation of malignant lesions. Here, we aimed to identify cell cycle phases and apoptosis using immunohistochemistry in oral epithelial precursor lesions and oral squamous cell carcinoma. Methods Chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A histone family member X expression levels were immunohistochemically examined in tissue specimens from 55 patients with oral epithelial precursor lesions and 50 patients with oral squamous cell carcinoma. Associations of clinicopathological variables with marker expression were assessed. Results Chromatin licensing and DNA replication factor 1 was expressed in the prickle cell layer of oral epithelial precursor lesions and many carcinoma cells of oral squamous cell carcinoma. Geminin reactivity was widely distributed in high‐grade dysplasia and oral squamous cell carcinoma rather than low‐grade or no dysplastic cases. γ‐H2A histone family member X was expressed in the superficial layer of oral epithelial precursor lesions and scattered carcinoma cells of oral squamous cell carcinoma. In oral squamous cell carcinoma, lower geminin expression was observed in recurrent cases. Geminin and γ‐H2A histone family member X were associated with the degree of differentiation and mode of invasion. Conclusion Chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A histone family member X expression levels were correlated with oral carcinogenesis; these markers were associated with clinicopathological behaviors in oral squamous cell carcinoma.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 88%

Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

Siril

Kouketsu

Oikawa

et al. 2019

J Oral Pathology Medicine

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“…1,2 The pathogenesis of HCC is very complicated with lots of genes and proteins to participate in. [3][4][5] The advanced clinical stage system is the only accepted method for predicting the prognosis of clinical HCC patients with progressive disease, with surgery being the only major therapeutic option. Diagnosis of HCC is usually dependant on image techniques, blood indicators, and histopathology.…”

Section: Introductionmentioning

confidence: 99%

miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker

Li¹,

Wang²,

Zhu³

et al. 2018

IJN

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BackgroundMicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC).MethodsIn this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo.ResultsWe found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC.ConclusionThese findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.

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“…Overexpression of Cdc6 and Cdt1 has been shown to contribute to oncogenesis 6, 7 and their upregulations are linked to cancer progression in various types of cancer 8–13 . Cdc6 has been shown to be regulated by estrogen 14 , and is downregulated in methionine-mediated inhibition of cell proliferation 15 .…”

Section: Introductionmentioning

confidence: 99%

The prognostic significance of Cdc6 and Cdt1 in breast cancer

Mahadevappa

Neves

Yuen

et al. 2017

Sci Rep

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DNA replication is a critical step in cell proliferation. Overexpression of MCM2-7 genes correlated with poor prognosis in breast cancer patients. However, the roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in breast cancers are largely unknown. In the present study, we have shown that the expression levels of Cdc6 and Cdt1 were both significantly correlated with an increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort (n = 1441). In line with this finding, the expression of Cdc6 and Cdt1 was upregulated in breast cancer cells compared to normal breast epithelial cells. Expression of Cdc6 and Cdt1 was significantly higher in ER negative breast cancer, and was suppressed when ER signalling was inhibited either by tamoxifen in vitro or letrozole in human subjects. Importantly, breast cancer patients who responded to letrozole expressed significantly lower Cdc6 than those patients who did not respond. Our results suggest that Cdc6 is a potential prognostic marker and therapeutic target in breast cancer patients.

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Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma

Abstract: Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma.

Cited by 37 publications

References 34 publications

Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ‐H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker

The prognostic significance of Cdc6 and Cdt1 in breast cancer

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