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      Expression and Prognostic Value of Lgr5 in Patients with Recurrent Nasopharyngeal Carcinoma

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          Abstract

          Background

          As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous.

          Materials

          We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis.

          Results

          Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively).

          Conclusion

          Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients.

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          Most cited references35

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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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            Nasopharyngeal carcinoma

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              Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro.

              The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Wnt target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle. Here, we investigated Lgr5 expression in the stomach and assessed the stem cell potential of the Lgr5(+ve) cells by using in vivo lineage tracing. In neonatal stomach, Lgr5 was expressed at the base of prospective corpus and pyloric glands, whereas expression in the adult was predominantly restricted to the base of mature pyloric glands. Lineage tracing revealed these Lgr5(+ve) cells to be self-renewing, multipotent stem cells responsible for the long-term renewal of the gastric epithelium. With an in vitro culture system, single Lgr5(+ve) cells efficiently generated long-lived organoids resembling mature pyloric epithelium. The Lgr5 stem cell marker and culture method described here will be invaluable tools for accelerating research into gastric epithelial renewal, inflammation/infection, and cancer. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                25 May 2023
                2023
                : 16
                : 2023-2034
                Affiliations
                [1 ]Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Dehui Wang; Xicai Sun, Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University , 83 Fen Yang Road, Shanghai, People’s Republic of China, Email wangdehuient@sina.com; laryngeal@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-1423-0942
                http://orcid.org/0000-0003-0346-3193
                Article
                408991
                10.2147/IJGM.S408991
                10226542
                37256083
                8c313bd0-caf0-4a7a-a2d1-fbd50896d839
                © 2023 Xu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 03 March 2023
                : 28 April 2023
                Page count
                Figures: 5, Tables: 3, References: 35, Pages: 12
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: Shen Kang Hospital Development Center;
                Funded by: Clinical Research Plan of SHDC;
                Funded by: Science and Technology Commission of Shanghai Municipality, open-funder-registry 10.13039/501100003399;
                Funded by: Shanghai Municipal Health Commission;
                This work was financially supported by the National Natural Science Foundation of China (No. 81870703), Shanghai Shen Kang Hospital Development Center (SHDC12018118), Clinical Research Plan of SHDC (SHDC2020CR2005A), Science and Technology Commission of Shanghai Municipality (20Y11902000, 21ZR1411700, 23YF1404600), and Shanghai Municipal Health Commission (201940143).
                Categories
                Original Research

                Medicine
                recurrent nasopharyngeal carcinoma,cancer stem cell,lgr5,survival
                Medicine
                recurrent nasopharyngeal carcinoma, cancer stem cell, lgr5, survival

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