Diagnosis Accuracy and Prognostic Significance of the Dickkopf-1 Protein in Gastrointestinal Carcinomas: Systematic Review and Network Meta-analysis

Jiang, Xiaowen; Hui, Fuhai; Qin, Xiaochun; Wu, Yuting; Liu, Haihan; Gao, Jing; Li, Xiang; Xu, Yali; Zhang, Yingshi

doi:10.7150/jca.49970

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…The glycoprotein Dickkopf-1 (DKK-1), expressed mainly in the placenta and embryonic tissues, is an antagonist of the Wnt/β-catenin signaling pathway and is elevated in several cancer types. DKK-1 shows higher efficacy for detecting HCC than AFP in phase 4 trials ( 206 – 208 ), but midkine is more precise than DKK-1 in cirrhotic HCV patients ( 209 ). A combination of Golgi protein 73, AFP, and Dickkopf-1 increases the sensitivity and specificity of HCC detection ( 210 ).…”

Section: Promising New Biomarkers For Clinical Applicationmentioning

confidence: 99%

HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice

et al. 2022

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Hepatocellular carcinoma (HCC) is one of the most common and deadly tumors worldwide. Management of HCC depends on reliable biomarkers for screening, diagnosis, and monitoring of the disease, as well as predicting response towards therapy and safety. To date, imaging has been the established standard technique in the diagnosis and follow-up of HCC. However, imaging techniques have their limitations, especially in the early detection of HCC. Therefore, there is an urgent need for reliable, non/minimal invasive biomarkers. To date, alpha-fetoprotein (AFP) is the only serum biomarker used in clinical practice for the management of HCC. However, AFP is of relatively rather low quality in terms of specificity and sensitivity. Liquid biopsies as a source for biomarkers have become the focus of clinical research. Our review highlights alternative biomarkers derived from liquid biopsies, including circulating tumor cells, proteins, circulating nucleic acids, and exosomes, and their potential for clinical application. Using defined combinations of different biomarkers will open new perspectives for diagnosing, treating, and monitoring HCC.

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Section: Promising New Biomarkers For Clinical Applicationmentioning

confidence: 99%

HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice

et al. 2022

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“…( 115 , 116 ) However, the clinical utility of GP73 is limited by the lack of an FDA‐approved immunoassay that detects the specific glycosylated isoform associated with HCC. Other promising circulating biomarkers for the early diagnosis of HCC include osteopontin, ( 101 , 117 , 118 , 119 ) midkine, ( 120 , 121 , 122 , 123 , 124 ) Dickkopf‐1, ( 125 , 126 ) squamous cell carcinoma antigen, ( 127 , 128 ) and fibronectin. ( 129 , 130 ) These biomarkers need further validation in large, multicenter studies that include patients with HCCs arising from different etiologies.…”

Section: What Are the Current And Emerging Circulating Biomarkers For Hcc Surveillance?mentioning

confidence: 99%

Current and Emerging Tools for Hepatocellular Carcinoma Surveillance

Adeniji

Dhanasekaran

2021

Hepatol Commun

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Early detection of HCC enables patients to avail curative therapies that can improve patient survival. Current international guidelines advocate for the enrollment of patients at high risk for HCC, like those with cirrhosis, in surveillance programs that perform ultrasound every 6 months. In recent years, many studies have further characterized the utility of established screening strategies and have introduced new promising tools for HCC surveillance. In this review, we provide an overview of the most promising new imaging modalities and biomarkers for the detection of HCC. We discuss the role of imaging tools like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) in the early detection of HCC, and describe recent innovations which can potentially enhance their applicability, including contrast enhanced ultrasound, low-dose CT scans, and abbreviated MRI. Next, we outline the data supporting the use of three circulating biomarkers (i.e., alpha-fetoprotein [AFP], AFP lens culinaris agglutinin-reactive fraction, and des-gamma-carboxy prothrombin) in HCC surveillance, and expand on multiple emerging liquid biopsy biomarkers, including methylated cell-free DNA (cfDNA), cfDNA mutations, extracellular vesicles, and circulating tumor cells. These promising new imaging modalities and biomarkers have the potential to improve early detection, and thus improve survival, in patients with HCC. (Hepatology Communications 2021;5:1972-1986).L iver cancer is the sixth most common cancer worldwide and is now the third-leading cause of cancer-related death, behind lung cancer and colorectal cancer. (1) In 2020, more than 900,000 cases of liver cancer were diagnosed globally, with more than 830,000 liver cancer-related deaths, underscoring the high mortality index of this cancer. (1) Hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancers. The global incidence of HCC has increased by more than 75% in the last 30 years, especially in Western countries, (2)(3)(4) and is expected to continue to grow in the near future. Unfortunately, survival rates for patients with HCC in the United States remain dismally low and essentially unchanged over the past 30 years, (5) with only 3%-34% of patients with HCC surviving 5 years after diagnosis. (6) The high HCC mortality rates can be attributed to several factors, with delayed diagnosis of cancer at more advanced stages of disease being an important reason. (2,7,8) HCC typically arises in the background of the cirrhotic liver, where chronic inflammation and fibrosis induce genomic alterations that render the hepatocytes vulnerable to malignant transformation. (9)(10)(11) The presence of cirrhosis is the strongest risk factor for HCC, with 90% of HCCs arising in cirrhotic livers. The

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“…In vitro and in vivo studies showed that activator protein-1 (AP-1) controlled tumor growth, progression and drug resistance[ 10 , 11 ]. DKK1 is a potent antagonist that suppresses oncogenic Wnt/β-catenin signaling and tumors by binding to the Wnt coreceptor: low-density lipoprotein receptor-related protein (LRP) 5/6[ 12 , 13 ]. However, recent studies demonstrated that DKK1 behaved like an oncogene in a variety of cancers[ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway

Luo

Chen

Xie

et al. 2022

World J Gastroenterol

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BACKGROUND Gastric cancer (GC) is a common malignant tumor with high incidence and mortality rates globally, especially in East Asian countries. Helicobacter pylori ( H. pylori ) infection is a significant and independent risk factor for GC. However, its underlying mechanism of action is not fully understood. Dickkopf-related protein (DKK) 1 is a Wnt signaling antagonist, and cytoskeleton-associated protein (CKAP) 4 is a newly identified DKK1 receptor. Recent studies found that the binding of DKK1 to CAKP4 mediated the procancer signaling of DKK1 inde-pendent of Wnt signaling. We hypothesize that H. pylori -induced activation of DKK1/CKAP4 signaling contributes to the initiation and progression of GC. AIM To investigate the interaction of H. pylori infection, DKK1 and CAKP4 in GC, as well as the underlying molecular mechanisms. METHODS RNA sequencing was used to identify differentially expressed genes (DEGs) between H. pylori -infected and uninfected primary GC cells. Gain- and loss-of-function experiments were performed to verify the H. pylori -induced upregulation of activator protein-1 (AP-1) in GC cells. A dual-luciferase reporter assay and co-immunoprecipitation were used to determine the binding of AP-1 to the DKK1 promoter and DKK1 to CKAP4. Western blotting and immunohistochemistry detected the expression of DKK1, CKAP4, and phos-phatidylinositol 3-kinase (PI3K) pathway-related proteins in GC cells and tissues. Functional experiments and tumorigenicity in nude mice detected malignant behavior of GC cells in vitro and in vivo . RESULTS We identified 32 DEGs between primary GC cells with and without H. pylori infection, including JUN, fos-like antigen-1 (FOSL1), and DKK1, and confirmed that the three proteins and CKAP4 were highly expressed in H. pylori -infected GC cells, H. pylori -infected gerbil gastric tissues, and human GC tissues. JUN and FOSL1 form AP-1 to transcriptionally activate DKK1 expression by binding to the DKK1 promoter. Activated DKK1 bound to CKAP4, but not the most common Wnt coreceptor low-density lipoprotein receptor-related protein 5/6, to promote GC cell growth, colony formation, migration, invasion, and xenograft tumor growth in nude mice. All these effects were driven by activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. Targeting the PI3K signaling pathway by LY294002 inhibited DKK1-mediated CKAP4/PI3K signaling activity and the malignant behavior of GC cells. CONCLUSION H. pylori induces JUN and FOSL1 expression to form AP-1, which transcriptionally activates DKK1. Binding of DKK1 to KAKP4 contributes to gastric tumorige...

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Diagnosis Accuracy and Prognostic Significance of the Dickkopf-1 Protein in Gastrointestinal Carcinomas: Systematic Review and Network Meta-analysis

Cited by 10 publications

References 51 publications

HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice

HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice

Current and Emerging Tools for Hepatocellular Carcinoma Surveillance

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway

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