Authors: Zhang, Jun | Yu, Xiao-Ling | Zheng, Guo-Feng | Zhao, Fei
Article Type: Research Article
Abstract: OBJECTIVE: This meta-analysis investigated the correlation between the promoter methylation of death-associated protein kinase (DAPK ) and the clinicopathological features in patients with non-small cell lung cancer (NSCLC). METHOD: Scientific literature databases were exhaustively searched to retrieve published studies relevant to DAPK methylation and NSCLC. Retrieved studies published in English and Chinese languages were screened according to the stringent predefined inclusion and exclusion criteria, and high quality studies were selected for meta-analysis. All statistical analyses were performed utilizing STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). RESULTS: A total of 14 published studies (5 in English and 9 …in Chinese) were enrolled in the present meta-analysis, and contained 1238 patients with NSCLC. The results indicated that NSCLC patients with metastatic phenotype were strongly associated with significantly higher methylation rate of DAPK compared to NSCLC patients without metastasis. Additionally, in NSCLC patients carrying tumors with DAPK methylation, the 5-year survival rate was remarkedly lower than NSCLC patients without DAPK methylation. However, we did not find significant correlation between DAPK methylation and histological stage or tumor node metastasis (TNM) stage in NSCLC patients. CONCLUSION: Our meta-analysis results reveal that DAPK promoter methylation might be associated with tumor metastasis and poor prognosis in NSCLC patients, although no correlation with histological types and TNM stage in NSCLC patients were found. Show more
Keywords: Death-associated protein kinase (DAPK), non-small cell lung cancer, clinicopathological features, prognosis, meta-analysis
DOI: 10.3233/CBM-150501
Citation: Cancer Biomarkers, vol. 15, no. 5, pp. 609-617, 2015
Authors: Yang, Liu | Wang, Tiejun | Zhang, Jun | Liu, Zhonghao | Wang, Xuxia
Article Type: Research Article
Abstract: BACKGROUND: BTB/POZ domain-containing protein 7 (BTBD7) is recognized as a regulatory gene that regulates epithelial cell dynamics and branching morphogenesis. It is also reported for regulating epithelial-mesenchymal transition (EMT) molecules and involved in the process of invasion and metastasis of lung cancer and hepatocellular carcinoma. Slug is a transcriptional factor of EMT which plays a crucial role in the process of primary salivary adenoid cystic carcinoma (SACC). However, the role of BTBD7 in SACC and the correlation with Slug have not been identified. This study investigated the expression of BTBD7 and correlation with Slug, as well as the prognostic significance …of BTBD7 in SACC. METHODS: The expression of BTBD7 and Slug were examined in ACC-LM and ACC-83 cell lines and immunohistochemically in paraffin embedded tissue specimens from 66 primary SACC patients. Statistical analyses were performed to evaluate the correlation between BTBD7 expression and Slug expression and the prognostic significance of BTBD7 expression. RESULTS: BTBD7 protein expression was initially verified in ACC-LM and ACC-83 cell lines. The positive rate of BTBD7 expression was 62.1% in SACC to 20% in normal salivary tissues comparatively. BTBD7 expression was significantly correlated with Slug expression in SACC (P< 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients' poor clinical outcome. CONCLUSIONS: Positive expression of BTBD7 in SACC could play an important role in the development of cancer and may serve as a favorable predictor for diagnosis and poor prognosis of patients. Show more
Keywords: BTBD7, Slug, salivary adenoid cystic carcinoma, prognosis
DOI: 10.3233/CBM-160629
Citation: Cancer Biomarkers, vol. 17, no. 2, pp. 179-185, 2016
Authors: Yang, Liu | Wang, Tiejun | Zhang, Jun | Wang, Xuxia
Article Type: Research Article
Abstract: BACKGROUND: Epithelial-mesenchymal transition (EMT) is a complicated process that has been implicated in cancer progression and metastasis as well as the formation of many tissues and organs. BTB/POZ domain-containing protein 7 (BTBD7) is reported to regulate transcriptional factors and involved in the process of invasion and metastasis of some malignant tumors. Additionally, our preliminary studies have confirmed that BTBD7 expression was significantly correlated with Slug expression and poor prognosis of primary salivary adenoid cystic carcinoma (SACC). On this basis, this study further investigated function of BTBD7 in the invasion and metastasis of SACC in vitro , which may be a …possible target of gene therapy in the future. METHODS: The expression of BTBD7 and Slug were both examined in SACC-LM and SACC-83 cell lines by immunofluorescence staining. High invasive SACC-LM cells were transfected with BTBD7 siRNA and the expression levels of BTBD7 and Slug were detected in both gene and protein levels by qRT-PCR and western blot analysis. Assays were performed to survey cell migration, invasion and proliferation capabilities with BTBD7 silencing. RESULTS: BTBD7 and Slug proteins were detected in SACC-LM and SACC-83 cell lines. BTBD7 silencing down-regulated the expression of Slug and MMP9 meanwhile up-regulated the expression of E-cadherin in SACC-LM cells, the migration and invasion abilities of cells were obviously suppressed but with no influence on cell proliferation. CONCLUSIONS: BTBD7 silencing inhibited EMT through regulation of Slug expression in SACC-LM cells and might act as a potential molecular target for gene therapy of SACC. Show more
Keywords: BTBD7, Slug, salivary adenoid cystic carcinoma, RNA interference
DOI: 10.3233/CBM-170262
Citation: Cancer Biomarkers, vol. 20, no. 4, pp. 461-468, 2017
Authors: Chen, Zheng-Lin | Ma, Ying-Yu | Mou, Xiao-Zhou | Zhang, Jun-Gang
Article Type: Research Article
Abstract: OBJECTIVE: MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC. METHODS: In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored. RESULTS: High mRNA level of …MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels. CONCLUSION: MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment. Show more
Keywords: MED7, hepatocellular carcinoma, tumorigenesis, progression
DOI: 10.3233/CBM-220439
Citation: Cancer Biomarkers, vol. 38, no. 4, pp. 603-611, 2023
Authors: Zhong, Hong | Feng, Yi | Zheng, Gui-Xiong | Liang, Yan | Zhang, Jun-Yuan | Zheng, Bao-Shi | Feng, Xu
Article Type: Research Article
Abstract: Background: Results of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the adenocarcinomas of lung cancer are still debated. Objective: This meta-analysis was performed to evaluate the association between GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. Methods: The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Results: 16 reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and the risk of adenocarcinomas of lung cancer. The G allele and GG genotype were not …associated with the susceptibility of risk of adenocarcinomas. Furthermore, in the sensitivity analysis, the results were similar with those from the non-sensitivity analysis. Conclusions: GSTP1 G allele or GG genotype is not a biomarker to be associated with the susceptibility of adenocarcinomas of lung cancer. Show more
Keywords: Lung cancer, adenocarcinomas, glutathione S-transferase P1, A/G gene polymorphism, meta-analysis
DOI: 10.3233/CBM-130322
Citation: Cancer Biomarkers, vol. 13, no. 1, pp. 29-35, 2013
Authors: Abou-Fadel, Johnathan | Grajeda, Brian | Jiang, Xiaoting | Cailing-De La O, Alyssa-Marie D. | Flores, Esmeralda | Padarti, Akhil | Bhalli, Muaz | Le, Alexander | Zhang, Jun
Article Type: Research Article
Abstract: Breast cancer is the most diagnosed cancer worldwide and remains the second leading cause of cancer death. While breast cancer mortality has steadily declined over the past decades through medical advances, an alarming disparity in breast cancer mortality has emerged between African American women (AAW) and Caucasian American women (CAW). New evidence suggests more aggressive behavior of triple-negative breast cancer (TNBC) in AAW may contribute to racial differences in tumor biology and mortality. Progesterone (PRG) can exert its cellular effects through either its classic, non-classic, or combined responses through binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane …PRG receptors (mPRs), warranting both pathways equally important in PRG-mediated signaling. In our previous report, we demonstrated that the CCM signaling complex (CSC) consisting of CCM1, CCM2, and CCM3 can couple both nPRs and mPRs signaling cascades to form a CSC-mPRs-PRG-nPRs (CmPn) signaling network in nPR positive(+ ) breast cancer cells. In this report, we furthered our research by establishing the CSC-mPRs-PRG (CmP) signaling network in nPR(- ) breast cancer cells, demonstrating that a common core mechanism exists, regardless of nPR(+ / - ) status. This is the first report stating that inducible expression patterns exist between CCMs and major mPRs in TNBC cells. Furthermore, we firstly show mPRs in TNBC cells are localized in the nucleus and participate in nucleocytoplasmic shuttling in a coordinately synchronized fashion with CCMs under steroid actions, following the same cellular distribution as other well-defined steroid hormone receptors. Finally, for the first time, we deconvoluted the CmP signalosome by using systems biology and TNBC clinical data, which helped us understand key factors within the CmP network and identify 6 specific biomarkers with potential clinical applications associated with AAW-TNBC tumorigenesis. These novel biomarkers could have immediate clinical implications to dramatically improve health disparities among AAW-TNBCs. Show more
Keywords: Triple negative breast cancers, African American women, classic nuclear progesterone receptors, non-classic membrane progesterone receptors, cytoplasmic-nuclear trafficking, biomarkers, cancer therapy, CCM signaling complex, tumorigenesis, progesterone, mifepristone
DOI: 10.3233/CBM-210351
Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 607-636, 2022