MEKK3 and Survivin Expression in Cervical Cancer: Association with Clinicopathological Factors and Prognosis

Cao, Xuequan; Lu, Hongsheng; Zhang, Ling; Chen, Lili; Gan, Meifu

doi:10.7314/apjcp.2014.15.13.5271

Cited by 27 publications

(31 citation statements)

References 26 publications

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“…High recurrence rate, chemotherapeutic resistance with reduced survival is more common with advanced cervical cancer. Early diagnosis, targeted therapy, and prediction of prognosis are of great clinical significance (13). Therefore, the use of biomarkers that can predict the progression of tumor and evaluate the therapeutic strategies is mandatory (14).…”

Section: Discussionmentioning

confidence: 99%

Ezh2, endothelin-1, and cd34 as biomarkers of aggressive cervical squamous cell carcinoma: an immunohistochemical study

Fathy

Abdelrahman²

2018

TJPATH

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Objective: Cervical cancer has an increasing incidence in developing countries with a predominance of squamous cell carcinoma. In this work, we aimed to analyze the role of EZH2, Endothelin-1, and CD34 as indicators of the aggressiveness in cervical squamous cell carcinoma. Material and Method:Immunohistochemical expression of EZH2, Endothelin-1, and CD34 was studied in 54 paraffin-embedded tissue specimens of cervical squamous cell carcinoma. Their correlation to the clinicopathologic features and the potential angiogenic role were analyzed.Results: High EZH2 expression was noted in 78% of cervical squamous cell carcinoma with a significant relation with tumor grade, FIGO stage and lymph node metastasis (p=<0.001, p=0.007, p=0.03 respectively). Endothelin-1 overexpression was detected in 63% of the studied cases with a significant association with tumor size, FIGO stage and lymph node metastasis (p=0.009, p=0.002, p=0.02 respectively). High CD34 expression (MVD) was noted in 56% of the cases and associated with the tumor size, FIGO stage and lymph node metastasis (p<0.001, p<0.001, p=0.04 respectively). The three markers were significantly associated (p<0.05).Conclusion: EZH2, ET-1, and CD34 may act as biomarkers of aggressive cervical squamous cell carcinoma. They may contribute to the signaling pathway of angiogenesis. Therefore, they could potentially be used in targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Ezh2, endothelin-1, and cd34 as biomarkers of aggressive cervical squamous cell carcinoma: an immunohistochemical study

Fathy

Abdelrahman²

2018

TJPATH

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“…With the impressive progress of the next-generation sequencing technology, various genetic alterations have been revealed, including the high-frequency mutations of genes and dysregulated signalling pathways in cancer [5]. Recently, numerous studies have shown the clinical importance of the messenger RNA expression in numerous cancers, including cervical cancer [6]. Messenger RNAs play pivotal roles in diverse physiological and pathological processes, such as differentiation, cell proliferation, development, apoptosis, and stress responses [7].…”

Section: Introductionmentioning

confidence: 99%

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

Zhao

Huang

Zou

et al. 2020

International Journal of Genomics

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Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.

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“…Studies have reported that survivin is usually overexpressed in multiple cancers, such as breast cancer, cervical cancer, bladder cancer and gliomas. Overexpression of survivin indicates poor prognosis and cancer progression [34][35][36][37]. As an anti-apoptotic protein, survivin inhibits mitochondrial cytochrome c release and activation of caspase-9 and caspase-3 [38,39].…”

Section: Figure7mentioning

confidence: 99%

miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin

et al. 2018

Cell Physiol Biochem

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Background/Aims: TNF-related apoptosis-inducing ligand (TRAIL) is a novel and low-toxic anti-tumor drug used for various cancers. However, cancer cells usually develop mechanisms to acquire the resistance against TRAIL. Among these changes, dysregulation of microRNAs (miRNAs) usually occurs in cancer cells and is responsible for induction of drug resistance. Methods: Expression of miR-494 in gastric cancer tissues and cell lines was detected by quantitative reverse transcriptase real time PCR (qRT-PCR) analysis. Effect of miR-494 on regulating the TRAIL sensitivity to gastric cancer cell lines was evaluated by MTT assays. Bioinformatics and luciferase reporter assays were used to confirm the regulation of miR-494 on survivin. Mitochondrial apoptosis pathway in gastric cancer cells was tested by western blot and flow cytometry analysis. Results: Obvious downregulation of miR-494 was observed in gastric cancer cells. Furthermore, we found that expression profile of miR-494 was associated with TRAIL-sensitivity in gastric cancer. Enforced expression of miR-494 was found to sensitize the gastric cancer cells to TRAIL-induced cytotoxicity. Mechanically, Luciferase reporter assays proved that survivin was the target of miR-494 in gastric cancer cells. Enforced expression of miR-494 decreased the expression of survivin, and thus promoted the TRAIL-induced mitochondria collapse and apoptosis pathway. Conclusion: MiR-494/survivin axis represents a potential mechanism which is responsible for TRAIL resistance in gastric cancer cells. Increasing the miR-494 expression may serve as a novel therapeutic strategy to sensitize gastric cancer cells to TRAIL treatment.

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MEKK3 and Survivin Expression in Cervical Cancer: Association with Clinicopathological Factors and Prognosis

Cited by 27 publications

References 26 publications

Ezh2, endothelin-1, and cd34 as biomarkers of aggressive cervical squamous cell carcinoma: an immunohistochemical study

Ezh2, endothelin-1, and cd34 as biomarkers of aggressive cervical squamous cell carcinoma: an immunohistochemical study

A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction

miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin

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