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      Downregulation of LHPP Expression Associated with AFP Acts as a Good Prognostic Factor in Human Hepatocellular Carcinoma

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          Abstract

          Background

          Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters.

          Methods

          Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test.

          Results

          Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue.

          Conclusions

          LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

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

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          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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            Global cancer statistics, 2012.

            Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)
            Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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              The diagnosis and treatment of hepatocellular carcinoma.

              Justin Hartke, Matthew W. Johnson, Marwan Ghabril (2017)
              Hepatocellular carcinoma is a leading cancer worldwide. Its incidence is increasing, and is closely related to advanced liver disease. Cirrhosis represents the greatest risk factor for this malignancy, and is the main indication for screening and surveillance. The diagnosis of hepatocellular carcinoma can frequently, and uniquely, be made on characteristic multiphase contrast based cross-sectional imaging rather than strict need for tissue sampling. Despite advances in medical, locoregional and surgical therapies, hepatocellular carcinoma remains one of the most common causes of cancer-related death globally. In this review, current approaches to management of hepatocellular carcinoma are discussed, which incorporate both tumor and patient factors. The salient considerations in surgical (resection, liver transplantation), locoregional (ablation and embolic therapies) and medical therapies are highlighted.
              Article 0 comments Cited 296 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chao Jiang:
                ORCID: https://orcid.org/0000-0001-8345-1840
                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date Collection: 2021
                Publication date (Electronic): 25 August 2021
                Volume: 2021
                Electronic Location Identifier: 1971048
                Affiliations
                1The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, China
                2The College of Basic Medicine Sciences, Shaanxi University of Chinese Medicine, Xianyang 712046, China
                3The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710038, China
                Author notes

                Academic Editor: Qian Wang

                Author information
                https://orcid.org/0000-0001-5520-4834
                https://orcid.org/0000-0001-8345-1840
                Article
                DOI: 10.1155/2021/1971048
                PMC ID: 8416364
                PubMed ID: 34485511
                SO-VID: 49234595-18ab-4263-a195-936017466e32
                Copyright © Copyright © 2021 Xu Chao et al.
                License:

                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
                Date received : 13 May 2021
                Date accepted : 12 August 2021
                Funding
                Funded by: Subject Innovation Team of the Second Affiliated Hospital of Shaanxi University of Chinese Medicine
                Award ID: 2020XKTD-A01
                Funded by: Subject Innovation Team of Shaanxi University of Chinese Medicine
                Award ID: 2019-YS05
                Funded by: Science and Technology Program of Shaanxi Province
                Award ID: 2020SF-324
                Funded by: National Natural Science Foundation of China
                Award ID: 81774132
                Categories
                Subject: Research Article

                Data availability:

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