Differential proteome profiling of pleural effusions from lung cancer and benign inflammatory disease patients

Wang, Zhengyang; Wang, Cheng; Huang, Xiaobin; Shen, Ying; Shen, Jing; Ying, Kejing

doi:10.1016/j.bbapap.2012.01.016

Cited by 49 publications

(57 citation statements)

References 28 publications

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“…Previously, we created a comprehensive MPE proteome data set with 482 proteins and established the clinical relevance of potential biomarkers in NSCLC (9). Wang et al recently also identified 16 differentially expressed proteins between lung adenocarcinoma and benign inflammatory PEs by two-dimensional difference gel electrophoresis combined with MALDI-TOF (39). We identified/quantified 15 of 16 (93.75%) differently expressed proteins reported by Wang et al, and only one protein, Jumonji domain containing five, has not been identified in our PE proteome (supplemental Table S18).…”

Section: Discussionmentioning

confidence: 65%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 65%

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Liu

Chen

Wang³

et al. 2015

Molecular & Cellular Proteomics

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“…Consistent with these findings, biochemical assays of JMJD5 were unable to detect demethylation of H3K36me or other methyllysines in the N-terminal tails of histones H3 and H4. Based on these results and those recently published by other groups (38,49,53), it appears that JMJD5 does not possess intrinsic demethylase activity in vitro but may function as a protein hydroxylase.…”

mentioning

confidence: 74%

“…In a JMJD5 knockout mouse, loss of JMJD5 upregulated expression of the tumor suppressor p53, resulting in the activation of the p53-target genes encoding p21 and the proapoptotic protein Noxa without an appreciable change in the global H3K36me2 level (38). Similarly, a proteomic analysis of pleural effusions from patients with lung cancer and benign inflammatory disease identified decreased levels of JMJD5 but found that its overexpression in lung adenocarcinoma cells did not alter the global status of H3K36me1, H3K36me2, or H3K36me3 in vivo (49). In a separate study, JMJD5 overexpression failed to yield discernible alterations in mono-, di-, and trimethylation of H3K4, H3K9, H3K27, H3K36, and H3K79, as determined by immunoblotting and immunofluorescence analysis (53).…”

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confidence: 99%

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Crystal Structure and Functional Analysis of JMJD5 Indicate an Alternate Specificity and Function

Rizzo

Krishnan

Trievel

2012

Molecular and Cellular Biology

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JMJD5 is a Jumonji C (JmjC) protein that has been implicated in breast cancer tumorigenesis, circadian rhythm regulation, embryological development, and osteoclastogenesis. Recently, JMJD5 (also called KDM8) has been reported to demethylate dimethylated Lys-36 in histone H3 (H3K36me2), regulating genes that control cell cycle progression. Here, we report high-resolution crystal structures of the human JMJD5 catalytic domain in complex with the substrate 2-oxoglutarate (2-OG) and the inhibitor N-oxalylglycine (NOG). The structures reveal a ␤-barrel fold that is conserved in the JmjC family and a long shallow cleft that opens into the enzyme's active site. A comparison with other JmjC enzymes illustrates that JMJD5 shares sequence and structural homology with the asparaginyl and histidinyl hydroxylase FIH-1 (factor inhibiting hypoxia-inducible factor 1 [HIF-1]), the lysyl hydroxylase JMJD6, and the RNA hydroxylase TYW5 but displays limited homology to JmjC lysine demethylases (KDMs). Contrary to previous findings, biochemical assays indicate that JMJD5 does not display demethylase activity toward methylated H3K36 nor toward the other methyllysines in the N-terminal tails of histones H3 and H4. Together, these results imply that JMJD5 participates in roles independent of histone demethylation and may function as a protein hydroxylase given its structural homology with FIH-1 and JMJD6.T he Jumonji C (JmjC) enzymes represent a family of nonheme Fe(II)-and 2-oxoglutarate (2-OG)-dependent dioxygenases (5, 12). These enzymes belong to the Cupin protein superfamily whose members share a conserved ␤-barrel fold and possess a His-X-Glu/Asp-X n -His triad responsible for Fe(II) coordination (11,20,33,40). Metazoan JmjC proteins comprise several subfamilies that possess distinct substrate specificities and participate in different biological processes, including transcriptional regulation, cell cycle control, chromatin modification, mRNA splicing, and RNA modification (13,35,37,43,50). Enzymes from several of the JmjC subfamilies have been shown to function as lysine demethylases (KDMs) by hydroxylating the methyl groups of methyllysines in histones and nonhistone proteins. These subfamilies include JHDM1 (KDM2), JHDM2 (KDM3), JMJD2 (KDM4), JARID1, (KDM5), UTX/JMJD3 (KDM6), and PHF8/ KIAA1718 (KDM7) (2,22,35,45). In contrast, other JmjC enzymes catalyze stereo-and site-specific hydroxylation of residues in nonhistone proteins. Examples of these enzymes include JMJD6, a lysyl-5S-hydroxylase that oxidizes the splicing factor U2AF65 (32, 50), and FIH-1 (factor inhibiting hypoxia-inducible factor 1 [HIF-1]), an asparaginyl, aspartyl, and histidinyl hydroxylase whose substrates include the HIF and ankyrin repeat-containing proteins (13, 43, 51, 52). Moreover, recent studies have highlighted that JmjC substrates are not restricted to proteins. The tRNA wybutosine-synthesizing enzyme 5 (TYW5) hydroxylates wybutosine to hydroxywybutosine at position 37 in phenylalanine tRNA, illustrating that certain JmjC enzymes can oxidize nucleic...

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“…The results were consistent with the study by Liu et al (15), which showed decreased levels of TTR in the sera of lung cancer and benign lung disease patients compared to normal sera, and in addition, the decreased level of TTR in benign lung diseases was more evident compared to the patients with lung cancer. Recently, Wang et al (29) found a relatively increased level of TTR in the effusions and sera of lung cancer patients compared to the benign inflammatory disease samples. Collectively, the accumulated data indicated a potential value of TTR in lung cancer diagnosis.…”

Section: Serum Pleural Effusion -------------------------------------mentioning

confidence: 99%

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

et al. 2014

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Abstract. Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. IntroductionLung cancer is one of the most common malignant tumors worldwide, with a 5-year survival rate of 14% (1). Thus far, the statistics for cancer occurrence and outcome show that lung cancer remains a primary cause of mortality from cancer (2,3). Since the incidence and mortality of lung cancer increases significantly every year, it represents a major economic burden to society. Currently, the screening and early diagnosis of lung cancer in clinics relies mainly on magnetic resonance imaging (MRI) and computed tomography (CT) imaging, whereas the final diagnosis is established on the basis of histopathological examination results. The early clinical manifestations of lung cancer patients are relatively mild and not typical, easily overlooked or confused with benign inflammatory disease, such as lung infection. Therefore, early identification and diagnosis of lung cancer is significant since lung cancer may be curable in its early stages (1).Thus far, increasing attention has focused on searching for improved biomarkers that function not only to detect lung cancer at an early stage but also to explore the molecular mechanisms that underlie cancer development. Tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragments (Cyfra21-1), are clinically applied for the early detection of lung cancer (4,5). However, the sensitivity and specificity of these biomarkers are not adequate (6-8). Combined detection usi...

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Differential proteome profiling of pleural effusions from lung cancer and benign inflammatory disease patients

Cited by 49 publications

References 28 publications

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

In-depth Proteomic Analysis of Six Types of Exudative Pleural Effusions for Nonsmall Cell Lung Cancer Biomarker Discovery

Crystal Structure and Functional Analysis of JMJD5 Indicate an Alternate Specificity and Function

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

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