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      Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression

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          Abstract

          Background

          Ovarian cancer is the most fatal gynecologic malignancy worldwide due to its vagueness, delay in diagnosis, recurrence, and drug resistance. Therefore, a new type of ovarian cancer treatment prediction biomarker is urgently needed to supplement existing tools. A total of 230 people participated in this study. Out of this figure, 100 participants were patients who underwent an ovarian tumor operation, another 100 participants were ovarian benign patients, and the remaining 30 participants were healthy women. Cancer (experimental) group were 100 patients who underwent ovarian tumor operation, while the control groups were 130 participants consisting of 100 ovarian benign patients and 30 healthy women. Levels of SAA, carbohydrate antigen-125 (CA-125), and human epididymis protein 4 (HE4) were assessed using standard laboratory protocols. A total of 5 ovarian cancer tissues and paracancerous tissues were collected and then stored at − 80 °C until the qRT-PCR assay was conducted.

          Results

          The ROC curve of SAA concentration in ovarian cancer was plotted to obtain the area under the curve AUC = 0.889, the cut-off value 17.05 mg/L, the sensitivity 78.4% and specificity 86.5%. Compared with pretreatment, the level of serum SAA decreased significantly after treatment. The results revealed that there was a significant correlation between the level of serum SAA and advanced FIGO stage, histology subtype, lymphatic invasion, and distant metastasis ( p = 0.003,0.002,0.000 and 0.001). The quantitative Reverse transcription polymerase chain reaction (qRT-PCR) assay revealed that the Messenger RNA (mRNA) of SAA-1 and SAA-4 was much higher in cancer tissues than in adjacent tissues, and MMPs was up-regulation including MMP-1, MMP-9 and MMP- 12 in OVCAR-3 cell stimulated by SAA. The transwell assay revealed that SAA could promote OVCAR-3 cell migration. Moreover, SAA can regulate EMT markers and promote AKT pathway activation.

          Conclusions

          In summary, our results demonstrated that SAA may be a potential diagnosis and treatment prediction biomarker. The SAA promotes OVCAR-3 cell migration by regulating MMPs and EMT which may correlate with AKT pathway activation.

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          Most cited references35

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          Moving targets: Emerging roles for MMPs in cancer progression and metastasis.

          Matrix metalloproteinases have long been associated with cancer. Clinical trials of small molecule inhibitors for this family of enzymes however, were spectacularly unsuccessful in a variety of tumor types. Here, we discuss some of the newer roles that have been uncovered for MMPs in cancer that would not have been targeted with those initial inhibitors or in the patient populations analyzed. We also consider novel ways of using cancer-associated MMP activity for clinical benefit.
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            Hepatocytes direct the formation of a pro-metastatic niche in the liver.

            The liver is the most common site of metastatic disease 1 . While this metastatic tropism may reflect mechanical trapping of circulating tumor cells, liver metastasis is also dependent, at least in part, on formation of a “pro-metastatic” niche that supports tumor cell spread to the liver 2,3 . Mechanisms that direct formation of this niche, though, are poorly understood. Here, we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver, and in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. Early during pancreatic tumorigenesis, hepatocytes demonstrate activation of Signal Transducer and Activator of Transcription 3 (STAT3) signaling and increased production of serum amyloid A1 and A2 (SAA). Overexpression of SAA by hepatocytes also occurs in pancreatic and colorectal cancer patients with liver metastases, and many patients with locally advanced and metastatic disease display elevated levels of circulating SAA. STAT3 activation in hepatocytes and the subsequent production of SAA are dependent on interleukin 6 (IL-6) that is released into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6/STAT3/SAA signaling prevents establishment of a pro-metastatic niche and inhibits liver metastasis. Our data reveal an intercellular network underpinned by hepatocytes that forms the basis for a pro-metastatic niche in the liver and identify new therapeutic targets.
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              Can advanced-stage ovarian cancer be cured?

              Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer.
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                Author and article information

                Contributors
                renlitianjin@126.com
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                9 June 2020
                9 June 2020
                2020
                : 13
                : 67
                Affiliations
                [1 ]GRID grid.411918.4, ISNI 0000 0004 1798 6427, Department of Laboratory, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Human Genetic Resources Sharing Service Platform, , Tianjin Medical University Cancer Institute and Hospital, ; Tianjin, China
                [2 ]Department of Laboratory, the First Affiliated Hospital of Hebei North University, Hebei, China
                [3 ]GRID grid.265021.2, ISNI 0000 0000 9792 1228, School of Medical Laboratory, Tianjin Medical University, ; Tianjin, China
                Author information
                http://orcid.org/0000-0003-3689-3843
                Article
                669
                10.1186/s13048-020-00669-w
                7285470
                32517794
                f847470d-6dd8-4319-92c8-384f4aff1ace
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 21 December 2019
                : 27 May 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006606, Natural Science Foundation of Tianjin City;
                Award ID: 18JCZDJC32600
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81602026
                Award Recipient :
                Funded by: 863 plans sub-topics
                Award ID: 2015AA021107
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Obstetrics & Gynecology
                serum amyloid a,ovarian cancer,matrix metalloproteinases, epithelial–mesenchymal transition

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