Fibulin-4 is associated with tumor progression and a poor prognosis in ovarian carcinomas

Chen, Jie; Liu, Zhao; Fang, Shuang; Fang, Rui; Liu, Xi; Zhao, Yong; Li, Xiangxin; Huang, Lei; Zhang, Jie

doi:10.1186/s12885-015-1100-9

Cited by 17 publications

(23 citation statements)

References 51 publications

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“…18,27 EFEMP2 expression was up-regulated in cervical carcinoma and ovarian cancer, and its overexpression was significantly associated with the patient's adverse clinical and pathological characteristics and poor prognosis. 16,17 However, there were some opposite conclusions in the study of other tumors. EFEMP2 was weakly expressed in prostate carcinoma cell lines compared to normal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] The role of EFEMP2 in tumorigenesis has not yet been fully elucidated, both carcinogenic and anti-carcinogenic effects have been reported. High expression of EFEMP2 was associated with tumor progress and poor prognosis in cervical carcinoma, 16 ovarian carcinoma, 17 glioblastoma 18 and osteosarcoma. 19 However, in human endometrial carcinoma, EFEMP2 demonstrated inhibitory effects in tumor invasion and metastasis.…”

Section: Introductionmentioning

confidence: 96%

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EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs

Song¹,

Li²,

Liu³

et al. 2020

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Background: Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer. Methods: The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up-or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo. Results: EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9. Conclusion: The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs

Song¹,

Li²,

Liu³

et al. 2020

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“…FBLN4 promoter methylation has frequently been found in lung cancers43 and melanoma cells 44. Other studies have reported that FBLN4 is overexpressed in tumors of the digestive system45–47 and in gynecological tumors;48–50 FBLN4 overexpression correlates with tumor progression and poor prognosis in these studies. In contrast, FBLN4 is downregulated in prostate cancer 51.…”

Section: Discussionmentioning

confidence: 50%

FBLN4 as candidate gene associated with long-term and short-term survival with primary glioblastoma

Li¹,

Li²,

Zhang³

et al. 2017

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BackgroundGlioblastoma multiforme (GBM) is the most common malignant and lethal type of primary central nervous system tumor in humans. In spite of its high lethality, a small percentage of patients have a relatively good prognosis, with median survival times of 36 months or longer. The identification of clinical subsets of GBM associated with distinct molecular genetic profiles has made it possible to design therapies tailored to treat individual patients.MethodsWe compared microarray data sets from long-term survivors (LTSs) and short-term survivors (STSs) to screen for prognostic biomarkers in GBM patients using the WebArrayDB platform. We focused on FBLN4, IGFBP-2, and CHI3L1, all members of a group of 10 of the most promising, differentially regulated gene candidates. Using formalin-fixed paraffin-embedded GBM samples, we corroborated the relationship between these genes and patient outcomes using methylation-specific polymerase chain reaction (PCR) for MGMT methylation status and quantitative reverse transcription PCR for expression of these genes.ResultsExpression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples (P<0.01). Furthermore, Kaplan–Meier analysis showed that the expression patterns of FBLN4 and IGFBP-2 serve as independent prognostic indicators for overall survival (P<0.01 and P<0.05, respectively).ConclusionTo our knowledge, this is the first report describing FBLN4 as a prognostic factor for GBM patient survival, demonstrating that increased GBM survival time correlates with decreased FBLN4 expression. Understanding FBLN4 expression patterns could aid in the creation of powerful tools to predict clinical prognoses of GBM patients.

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“…Comparison of human colon tumors and adjacent normal tissue showed that tumors had a 2–7 fold increase at the EFEMP2 mRNA level 10. In cervical and ovarian carcinoma,11,12 EFEMP2 was overexpressed in cancer tissues and significantly related to poor clinicopathological characteristics. EFEMP2 expression was also found to be upregulated in osteosarcoma tissues and highly invasive cell lines, where EFEMP2 acted as a promoter for the development of osteosarcoma 13.…”

Section: Discussionmentioning

confidence: 96%

EFEMP2 Inhibits Breast Cancer Invasion And Metastasis In Vitro And In Vivo

Kang¹,

Zhou²,

Xu³

et al. 2019

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BackgroundEGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) is an extracellular matrix (ECM) glycoprotein, which is regarded as potential prognostic biomarkers in some carcinoma. Little is known about the association of EFEMP2 and breast cancer.MethodsEFEMP2 expressions in normal breast tissue, benign fibroadenoma, breast cancer, the normal mammary epithelial cell line, and 4 different invasive breast cancer cell lines were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Expression and prognostic value of EFEMP2 in breast cancer were verified by the Public databases (Oncomine and Kaplan-Meier plotter database). Lentiviral vector with EFEMP2 cDNA was constructed and used to infect breast cancer cell lines to investigate the effects of EFEMP2 on the biological behavior of breast cancer cells by functional in vitro and in vivo assays.ResultsDown-regulated EFEMP2 expression was found in breast cancer tissues and cells, and low expression of EFEMP2 was associated with poor prognosis in patients with breast cancer. Analysis by the Public database leaded to the same conclusion. Up-regulated EFEMP2 expression significantly hampered the invasion and metastasis abilities of breast cancer cells and the process of epithelial interstitial transformation (EMT) via the Wnt/β-catenin pathway.ConclusionEFEMP2 expression was lower in breast cancer and closely related to the prognosis of patients, its anti-oncogenic roles indicated the underlying therapeutic target for the future treatment of breast cancer.

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Fibulin-4 is associated with tumor progression and a poor prognosis in ovarian carcinomas

Cited by 17 publications

References 51 publications

<p>EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs</p>

<p>EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs</p>

<em>FBLN4</em> as candidate gene associated with long-term and short-term survival with primary glioblastoma

<p>EFEMP2 Inhibits Breast Cancer Invasion And Metastasis In Vitro And In Vivo</p>

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