Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study

Shen, Qiujin; Fan, Jia; Yang, Xun; Tan, Ye-Xiong; Zhao, Weifeng; Xu, Yang; Wang, Ning; Niu, Yongdong; Wu, Zheng; Zhou, Ji; Qiu, Shuang–Jian; Shi, Ying‐Hong; Yu, Bin; Tang, Ning; Chu, Wei; Wang, Min; Wu, Jiangxue; Zhang, Z.; Yang, Shengli; Gu, Jianren; Wang, Hongyang; Qin, Wenxin

doi:10.1016/s1470-2045(12)70233-4

Cited by 357 publications

(331 citation statements)

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“…For example, circulating DKK1 levels have previously been evaluated as biomarkers for cancer as well as coronary atherosclerosis. 71 In addition, the knowledge gained from these studies may also lead to the identification of potential routes for intervention in PVD, before the development of PAH and PH associated with chronic lung diseases, including IPF and COPD. …”

Section: Discussionmentioning

confidence: 99%

Shared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease

et al. 2016

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Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant-derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction. By analyzing the genetic signatures and pathways associated with abnormal ABCG2 lung MPC phenotypes during PAH and evaluating them in lung-and skinderived MCs, we have identified potential predictor genes for detection of PAH as well as a targetable mechanism to restore MPCs and microvascular function. These studies are the first to explore the utility of expanding the study of ABCG2 MPC regulation of the pulmonary microvasculature to the epidermis, in order to identify potential markers for adult lung vascular disease, such as PAH.Keywords: mesenchymal progenitor cells, skin, lung, microvascular, pulmonary hypertension, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, BMPR2, Wnt signaling, LRP6, DKK1. Pulmonary vascular dysfunction or disease (PVD) is characterized by altered lung vascular structure and function. A significant loss of vascular-bed function, as seen in PVD, is thought to precede the clinical presentation of pulmonary hypertension (PH). 1 PH is associated with a wide array of comorbid conditions, such as systemic sclerosis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, and also occurs as a primary PVD known as either idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH). 2-4 PH is characterized by elevated pulmonary artery pressures and widespread vascular remodeling, including endothelial cell dysfunction and occlusion or rarefaction of the peripheral pulmonary microvasculature. 5-7 All forms of PH have a high mortality rate despite current therapeutic options. The current limited understanding of PVD as a predecessor to PH and lack of diagnostic approaches or criteria specific to preclinical PVD have hampered the study of the early stages of PVD in both rodent models and the clinical setting.Approximately 80% of HPAH patients have a known mutation in the gene bone morphogenetic protein receptor type 2 (BMPR2). BMPR2 mutation-associated PAH is an autosomal dominant disease with low penetrance (approx. 20%); hence, not all mutation carriers develop PAH. In addition, approximately 20% of patients initially labeled as having IPAH also have a mutation in BMPR2 and thus heritable disease. 8 In addition to ge...

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Section: Discussionmentioning

confidence: 99%

Shared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease

et al. 2016

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“…It is the fifth and seventh cause of death from cancer in men and women, respectively (Shen et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Incidence and mortality of liver cancer and their relationship with the human development index in the world

Arabsalmani¹,

Mirzaei²,

Ghoncheh³

et al. 2016

Biomed Res Ther

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Abstract-Background: Information on the incidence and mortality of liver cancer can be useful for health programs and research activities, and with regard to the possible role of the HDI and liver cancer, this study aimed to investigate incidence and mortality from the cancer and their relationship with the indicator and its components in 2012 in world. Methods: In this ecologic study, data were extracted from GLOBOCAN in 2012. Data on HDI and its components were extracted from the World Bank. The number and standardized incidence and mortality rates of liver cancer were reported by regions in the world. Data were analyzed by SPSS software and Correlation coefficient test. Results: There was a total of 782,451 incidence cases. Of these patients, 228, 082 cases (29.15 %) were women and 554, 369 cases (70.85 %) men, and there were 745,533 deaths. Of the deaths, 224, 492 cases (30.11 %) occurred in women and 521, 041 cases (69.89 %) men were recorded in the world in 2012. Results showed that there was a significant inverse correlation between age-specific incidence rate (ASIR) and HDI (r=-0.345, p≤0.001), as well significant inverse correlation was seen between age-specific mortality rate (ASMR), and HDI and its components. Conclusion: Liver cancer incidence and mortality are higher in the medium HDI countries. The relationship between the standardized incidence and mortality of liver cancer with HDI and its components, including life expectancy at birth, mean years of schooling and income level per person was significantly negative.

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“…In lung cancer, DKK1 was found to be a novel serologic and histochemical biomarker, as well as a therapeutic target (Yamabuki et al, 2007). Shen et al found DKK1 to be elevated in hepatocellular carcinoma, where it complemented measurement of AFP in the diagnosis of HCC (Shen et al, 2012). Kaba et al found that serum DKK-1 may represent a novel marker for bladder cancer determination and poor clinical outcome in Turkish patients (Kaba et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Next, the 35 remaining full manuscripts were retrieved for detailed evaluation. Finally, 10 manuscripts in total (Yamabuki et al, 2007;Jiang et al, 2009;Sheng et al, 2009;Sato et al, 2010;Shen et al, 2010;Soydinc et al, 2011;Tung et al, 2011;Lee et al, 2012;Shen et al, 2012;Shi et al, 2013), which consisted of 11 studies, were included for evaluation according to the inclusion and exclusion criteria. The remaining 25 studies were excluded because of: a) lack of sufficient data (n=5); b) duplicate publications (n=12); c) lack of a control group (n=3); d) being a review article (n=2); or e) printed in Chinese (n=3).…”

Section: Eligible Articles For Meta-analysismentioning

confidence: 99%

“…Along these lines, several groups have devoted time and energy to examining the utility of serum DKK1 as a cancer biomarker. Shen et al described a large-scale, multicenter validation study to assess the diagnostic accuracy of DKK1; they found that serum DKK1 could serve as a biomarker for the diagnosis of hepatocellular carcinoma (Shen et al, 2012). It may also be useful as a diagnostic marker in a number of cancers, including gastric, cervical, and endometrial cancers (Jiang et al, 2009;Lee et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Assessing the Diagnostic Value of Serum Dickkopf-related Protein 1 Levels in Cancer Detection: a Case-control Study and Meta-analysis

Jiang

Ma²,

Guo³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: This study aimed to summarize the potential diagnostic value of serum DKK1 levels in cancer detection. Materials and Methods: Serum DKK1 was measured using enzyme-linked immunosorbent assay in a case-control study. Then we performed a meta-analysis and the pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic (sROC) curves were used to evaluate the overall test performance. Results: Serum DKK1 levels were found to be significantly upregulated in gastric cancer as compared to controls. ROC curve analysis revealed an AUC of 0.636, indicating the test has the potential to diagnose cancer with poor accuracy. The summary estimates of the pooled sensitivity, specificity and diagnostic odds ratio in meta-analysis were 0.55 with a 95% confidence interval (

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Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study

Cited by 357 publications

References 33 publications

Shared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease

Shared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease

Incidence and mortality of liver cancer and their relationship with the human development index in the world

Assessing the Diagnostic Value of Serum Dickkopf-related Protein 1 Levels in Cancer Detection: a Case-control Study and Meta-analysis

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