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      Expression of Dickkopf-1 and Twist2 in Cervical Squamous Cell Carcinoma and Their Correlation with Vasculogenic Mimicry

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      Journal of Healthcare Engineering
      Hindawi

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          Abstract

          Wnt/ β-catenin signaling, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry (VM) all exert important effects in tumors. Dickkopf-1 (DKK1) is an antagonist of the Wnt/ β-catenin, Twist homolog 2 (Twist2) is a key EMT transcription factor involved in cancer cell migration and invasion, and VM participates in the progression and metastasis of a variety of cancers. However, the correlation of DKK1, Twist2, and VM in cervical squamous cell carcinoma(CSC) is still unclear. This study focuses on correlations among these factors as well as their correlation with clinicopathologic data and survival in CSC. DKK1, Twist2, and VM expressions were immunohistochemically examined in 116 CSC tissues and 37 normal cervical tissues. Furthermore, clinical data were processed. The expression levels of these three factors differed between CSC and normal tissues. VM was observed in CSC, but not in normal cervical tissues. Twist2 expression was high in CSC but low in normal cervical tissues, whereas DKK1 expression had the opposite pattern. Tumor cells with VM had a high expression of Twist2 and low expression of DKK1. In addition, DKK1 expression was negatively correlated with Twist2 expression. Analyzing the relationships of DKK1, Twist2, and VM with the data of patients with CSC revealed that DKK1 expression was negatively correlated with the clinical stage, degree of differentiation, depth of infiltration, and lymph node metastasis of tumors. VM and Twist2 expression were positively correlated with the degree of differentiation, the depth of infiltration, and lymph node metastasis. The positive rate of VM was greater in stage II than in stage I. The patients who expressed VM and Twist2 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, the patients who expressed DKK1 had an increased OS when compared with patients who did not show any DKK1 expression. Multivariate analysis indicated that the expressions of DKK1, Twist2, and VM were prognostic factors for CSC. VM and the expression of DKK1 and Twist2 can be the potential prognostic biomarkers and therapeutic targets for CSC.

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          Most cited references20

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry.

            Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.
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              Function and biological roles of the Dickkopf family of Wnt modulators.

              C Niehrs (2006)
              Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy). They encode secreted proteins that typically antagonize Wnt/beta-catenin signaling, by inhibiting the Wnt coreceptors Lrp5 and 6. Additionally, Dkks are high affinity ligands for the transmembrane proteins Kremen1 and 2, which also modulate Wnt signaling. Dkks play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer's disease.
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                Author and article information

                Contributors
                Journal
                J Healthc Eng
                J Healthc Eng
                JHE
                Journal of Healthcare Engineering
                Hindawi
                2040-2295
                2040-2309
                2022
                16 March 2022
                : 2022
                : 9288476
                Affiliations
                Department of Gynecological Oncology, The 1st Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
                Author notes

                Academic Editor: Bhagyaveni M.A

                Author information
                https://orcid.org/0000-0002-1404-2426
                https://orcid.org/0000-0001-5902-7003
                https://orcid.org/0000-0003-4991-0550
                https://orcid.org/0000-0002-5662-4723
                Article
                10.1155/2022/9288476
                8942658
                35340228
                a84d9c25-c06c-43ae-8e07-eb9402b06386
                Copyright © 2022 Beibei Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 January 2022
                : 13 February 2022
                : 15 February 2022
                Funding
                Funded by: Bengbu Medical College
                Award ID: BYKY1851ZD
                Categories
                Research Article

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