The Role of ZFX in Non-Small Cell Lung Cancer Development

Jiang, Mei; Xu, Shaofa; Yue, Wentao; Zhao, Xiaoting; Zhang, Lina; Wang, Yue

doi:10.3727/096504012x13548165987493

Cited by 13 publications

(6 citation statements)

References 7 publications

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“…ZFX is the X-linked version of a protein that plays a role in molecular sex determination [ 61 ], so it may not be surprising that we found sex-specific differences in its regulatory patterns. However, it has also been implicated in lung cancer [ 62 , 63 ]. Similarly CREB is over-expressed in many cancers, including lung cancer [ 64 ], and, interestingly, has been shown to interact with the estrogen receptor and to have age and sex- dependent expression patterns in the human brain [ 65 ].…”

Section: Resultsmentioning

confidence: 99%

Sexually-dimorphic targeting of functionally-related genes in COPD

et al. 2014

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BackgroundThere is growing evidence that many diseases develop, progress, and respond to therapy differently in men and women. This variability may manifest as a result of sex-specific structures in gene regulatory networks that influence how those networks operate. However, there are few methods to identify and characterize differences in network structure, slowing progress in understanding mechanisms driving sexual dimorphism.ResultsHere we apply an integrative network inference method, PANDA (Passing Attributes between Networks for Data Assimilation), to model sex-specific networks in blood and sputum samples from subjects with Chronic Obstructive Pulmonary Disease (COPD). We used a jack-knifing approach to build an ensemble of likely networks for each sex. By adapting statistical methods to compare these network ensembles, we were able to identify strong differential-targeting patterns associated with functionally-related sets of genes, including those involved in mitochondrial function and energy metabolism. Network analysis also identified several potential sex- and disease-specific transcriptional regulators of these pathways.ConclusionsNetwork analysis yielded insight into potential mechanisms driving sexual dimorphism in COPD that were not evident from gene expression analysis alone. We believe our ensemble approach to network analysis provides a principled way to capture sex-specific regulatory relationships and could be applied to identify differences in gene regulatory patterns in a wide variety of diseases and contexts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-014-0118-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Sexually-dimorphic targeting of functionally-related genes in COPD

et al. 2014

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“…Intriguingly, ZFX was recently revealed to be a transcriptional target of cyclin D1 [27], linking ZFX to an established oncogene product and oncogenic pathway in parathyroid and other cell types. Further, knockdown of ZFX has been reported to inhibit cellular proliferation in human laryngeal squamous cell carcinoma, gastric cancer, malignant glioma, non-small cell lung carcinoma and prostate cancer [28][29][30][31][32]. Finally, a solitary ZFX R786Q somatic mutation in endometrial carcinoma has been registered in the COSMIC database (endometrial cancer; mutation ID: COSM1119462).…”

Section: Discussionmentioning

confidence: 99%

Recurrent ZFX mutations in human sporadic parathyroid adenomas

Soong

Arnold

2014

Oncoscience

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ABSTRACT:The molecular abnormalities leading to sporadic parathyroid adenomas, a common type of human endocrine neoplasm, are heterogeneous and incompletely understood. Using whole exome and direct sequencing of parathyroid adenoma DNA samples, we identified recurrent somatic mutations in the ZFX gene. ZFX is a member of Krueppel C2H2 type zinc finger protein family, was initially described as a homolog of ZFY, and has been implicated as a transcription factor regulating embryonic stem cell renewal. The ZFX mutations we identified were strikingly specific, focused in each tumor on one encoded residue in a hotspot of two consecutive highly conserved arginine residues (R786/787; arginine to glutamine, threonine or leucine) in a zinc finger domain near the C-terminus of the protein. The intragenic specificity of these recurrently selected mutations, their confirmed expression within the tumors, the absence of loss of heterozygosity, and the absence of these mutations among over 4000 ZFX alleles in the dbSNP137 database, strongly suggest a novel role for ZFX as a human proto-oncogene. Further, these observations highlight the mutated zincfinger domain as a new focal point for understanding ZFX's normal and tumorigenic functions, and for development of molecularly-targeted therapeutics.

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“…Similar to these proteins, ZFX is a member of the zinc finger protein family. Previous studies have demonstrated that ZFX can function as an oncoprotein in various types of cancers, including gastric cancer [ 16 ], prostate cancer [ 24 , 25 ], glioma [ 26 ], hepatocellular cancer [ 30 ], gallbladder cancer [ 31 ], tongue squamous cell carcinoma [ 32 ], non-small cell lung cancer [ 33 ], and laryngeal squamous cell carcinoma [ 34 ]. However, few studies have focused on the prognostic significance of ZFX in RCC.…”

Section: Discussionmentioning

confidence: 99%

ZFX is a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma

Zhang

et al. 2015

Med Sci Monit

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BackgroundThis study was designed to assay the expression of zinc finger protein X-linked (ZFX) in renal cell carcinoma (RCC) tissues and evaluate the correlation between ZFX expression and prognosis of RCC patients.Material/MethodsThe expressions of ZFX mRNA in 53 RCC tissues and 51 normal tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) technology was used to measure the expression of ZFX protein. Then chi-square test was conducted to verify the association between ZFX expression and clinical parameters. Next, we explored the overall survival rate of RCC patients with Kaplan-Meier analysis. Finally, the correlation between ZFX expression and the prognosis of RCC patients was evaluated by Cox regression analysis.ResultsThe qRT-PCR result showed that the ZFX was significantly up-regulated in RCC tissues. As for the IHC consequence, the positive rate of ZFX expression in RCC specimens was 79.2%, while that in the normal control tissues was only 17.6%. Chi-square test showed that ZFX expression shared no close relationship with age, sex, or smoking (P>0.05), but was tightly associated with TNM stage, tumor size, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with ZFX positive expression had higher mortality than those with negative expression (P<0.05). Cox regression analysis revealed that ZFX expression had tight correlation with prognosis of RCC patients (HR=4.997, P=0.045, 95%CI=1.033–24.180).ConclusionsOur findings show that ZFX could be considered as a predictor for prognosis of RCC patients.

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The Role of ZFX in Non-Small Cell Lung Cancer Development

Cited by 13 publications

References 7 publications

Sexually-dimorphic targeting of functionally-related genes in COPD

Sexually-dimorphic targeting of functionally-related genes in COPD

Recurrent ZFX mutations in human sporadic parathyroid adenomas

ZFX is a Strong Predictor of Poor Prognosis in Renal Cell Carcinoma

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