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

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2021 Sep 6

PMID 34485511

Citations 2

Authors

Xu Chao

Wei Zhang

Jieqiong Wu

Xuesong Feng

Hailong Shi

Luyan Zhao

Haiyu Shen

Chao Jiang

Affiliations

Soon will be listed here.

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 -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.

Citing Articles

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

International B Biomed Res Int. 2024; 2024:9808126.

PMID: 38550199 PMC: 10973223. DOI: 10.1155/2024/9808126.

The histidine phosphatase LHPP: an emerging player in cancer.

Wu F, Ma H, Wang X, Wei H, Zhang W, Zhang Y Cell Cycle. 2022; 21(11):1140-1152.

PMID: 35239447 PMC: 9103355. DOI: 10.1080/15384101.2022.2044148.

References

Tang Q, Wang Q, Zhang Q, Lin S, Zhu Y, Yang X . Gene expression, regulation of DEN and HBx induced HCC mice models and comparisons of tumor, para-tumor and normal tissues. BMC Cancer. 2017; 17(1):862. PMC: 5735680. DOI: 10.1186/s12885-017-3860-x. View

Tian Z, Yu T, Wei H, Ning N . Clinical value of LHPP-associated microRNAs combined with protein induced by vitamin K deficiency or antagonist-II in the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma. J Clin Lab Anal. 2019; 34(2):e23071. PMC: 7031545. DOI: 10.1002/jcla.23071. View

Pani G, Galeotti T, Chiarugi P . Metastasis: cancer cell's escape from oxidative stress. Cancer Metastasis Rev. 2010; 29(2):351-78. DOI: 10.1007/s10555-010-9225-4. View

Liu Y, Zhang X, Yang B, Zhuang H, Guo H, Wei W . Demethylation-Induced Overexpression of Shc3 Drives c-Raf-Independent Activation of MEK/ERK in HCC. Cancer Res. 2018; 78(9):2219-2232. DOI: 10.1158/0008-5472.CAN-17-2432. View

Hartke J, Johnson M, Ghabril M . The diagnosis and treatment of hepatocellular carcinoma. Semin Diagn Pathol. 2017; 34(2):153-159. DOI: 10.1053/j.semdp.2016.12.011. View

Zheng J, Dai X, Chen H, Fang C, Chen J, Sun L . Down-regulation of LHPP in cervical cancer influences cell proliferation, metastasis and apoptosis by modulating AKT. Biochem Biophys Res Commun. 2018; 503(2):1108-1114. DOI: 10.1016/j.bbrc.2018.06.127. View

Neff C, Abkevich V, Packer J, Chen Y, Potter J, Riley R . Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Mol Psychiatry. 2008; 14(6):621-30. DOI: 10.1038/mp.2008.8. View

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

10.

Lesseur C, Diergaarde B, Olshan A, Wunsch-Filho V, Ness A, Liu G . Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nat Genet. 2016; 48(12):1544-1550. PMC: 5131845. DOI: 10.1038/ng.3685. View

11.

Xia J, Song P, Sun Z, Sawakami T, Jia M, Wang Z . Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma. Drug Discov Ther. 2016; 10(4):181-7. DOI: 10.5582/ddt.2016.01052. View

12.

Li L, Zhao G, Shi Z, Qi L, Zhou L, Fu Z . The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol Lett. 2016; 12(5):3045-3050. PMC: 5103898. DOI: 10.3892/ol.2016.5110. View

13.

Cui L, Gong X, Tang Y, Kong L, Chang M, Geng H . Relationship between the LHPP Gene Polymorphism and Resting-State Brain Activity in Major Depressive Disorder. Neural Plast. 2016; 2016:9162590. PMC: 5097818. DOI: 10.1155/2016/9162590. View

14.

Hindupur S, Colombi M, Fuhs S, Matter M, Guri Y, Adam K . The protein histidine phosphatase LHPP is a tumour suppressor. Nature. 2018; 555(7698):678-682. PMC: 6376988. DOI: 10.1038/nature26140. View