EPLIN Expression in Gastric Cancer and Impact on Prognosis and Chemoresistance

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2021 Apr 30

PMID 33917939

Citations 13

Authors

Wenjing Gong

Jianyuan Zeng

Jiafu Ji

Yongning Jia

Shuqin Jia

Andrew J Sanders

Wen G Jiang

Affiliations

Soon will be listed here.

Abstract

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC.

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References

Song Y, Maul R, Sachi Gerbin C, Chang D . Inhibition of anchorage-independent growth of transformed NIH3T3 cells by epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to actin cytoskeleton. Mol Biol Cell. 2002; 13(4):1408-16. PMC: 102278. DOI: 10.1091/mbc.01-08-0414. View

Liu R, Martin T, Jordan N, Ruge F, Ye L, Jiang W . Epithelial protein lost in neoplasm-α (EPLIN-α) is a potential prognostic marker for the progression of epithelial ovarian cancer. Int J Oncol. 2016; 48(6):2488-96. DOI: 10.3892/ijo.2016.3462. View

Szasz A, Lanczky A, Nagy A, Forster S, Hark K, Green J . Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget. 2016; 7(31):49322-49333. PMC: 5226511. DOI: 10.18632/oncotarget.10337. View

Collins R, Jiang W, Hargest R, Mason M, Sanders A . EPLIN: a fundamental actin regulator in cancer metastasis?. Cancer Metastasis Rev. 2015; 34(4):753-64. PMC: 4661189. DOI: 10.1007/s10555-015-9595-8. View

Tsurumi H, Harita Y, Kurihara H, Kosako H, Hayashi K, Matsunaga A . Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells. Kidney Int. 2014; 86(3):548-57. DOI: 10.1038/ki.2014.85. View

Jia Y, Ye L, Ji K, Zhang L, Hargest R, Ji J . Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy. Br J Cancer. 2013; 110(2):421-9. PMC: 3899757. DOI: 10.1038/bjc.2013.712. View

Ohashi T, Idogawa M, Sasaki Y, Tokino T . p53 mediates the suppression of cancer cell invasion by inducing LIMA1/EPLIN. Cancer Lett. 2017; 390:58-66. DOI: 10.1016/j.canlet.2016.12.034. View

Zhang S, Wang X, Osunkoya A, Iqbal S, Wang Y, Muller S . EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene. 2011; 30(50):4941-52. PMC: 3165108. DOI: 10.1038/onc.2011.199. View

Wu D . Epithelial protein lost in neoplasm (EPLIN): Beyond a tumor suppressor. Genes Dis. 2018; 4(2):100-107. PMC: 6136588. DOI: 10.1016/j.gendis.2017.03.002. View

10.

Coccolini F, Nardi M, Montori G, Ceresoli M, Celotti A, Cascinu S . Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg. 2018; 51:120-127. DOI: 10.1016/j.ijsu.2018.01.008. View

11.

Maul R, Song Y, Amann K, Gerbin S, Pollard T, Chang D . EPLIN regulates actin dynamics by cross-linking and stabilizing filaments. J Cell Biol. 2003; 160(3):399-407. PMC: 2172667. DOI: 10.1083/jcb.200212057. View

12.

Abe K, Takeichi M . EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt. Proc Natl Acad Sci U S A. 2007; 105(1):13-9. PMC: 2224173. DOI: 10.1073/pnas.0710504105. View

13.

Chen S, Maul R, Kim H, Chang D . Characterization of the human EPLIN (Epithelial Protein Lost in Neoplasm) gene reveals distinct promoters for the two EPLIN isoforms. Gene. 2000; 248(1-2):69-76. DOI: 10.1016/s0378-1119(00)00144-x. View

14.

Rizzo A, Mollica V, Ricci A, Maggio I, Massucci M, Rojas Limpe F . Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis. Future Oncol. 2019; 16(2):4409-4418. DOI: 10.2217/fon-2019-0429. View

15.

Jiang L, Yang K, Guan Q, Chen Y, Zhao P, Tian J . Survival benefit of neoadjuvant chemotherapy for resectable cancer of the gastric and gastroesophageal junction: a meta-analysis. J Clin Gastroenterol. 2014; 49(5):387-94. DOI: 10.1097/MCG.0000000000000212. View

16.

Zhang S, Wang X, Iqbal S, Wang Y, Osunkoya A, Chen Z . Epidermal growth factor promotes protein degradation of epithelial protein lost in neoplasm (EPLIN), a putative metastasis suppressor, during epithelial-mesenchymal transition. J Biol Chem. 2012; 288(3):1469-79. PMC: 3548460. DOI: 10.1074/jbc.M112.438341. View

17.

Zhitnyak I, Rubtsova S, Litovka N, Gloushankova N . Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition. Cells. 2020; 9(3). PMC: 7140442. DOI: 10.3390/cells9030578. View

18.

Chang D, Park N, Denny C, Nelson S, Pe M . Characterization of transformation related genes in oral cancer cells. Oncogene. 1998; 16(15):1921-30. DOI: 10.1038/sj.onc.1201715. View

19.

Hagen S, Ang L, Zheng Y, Karahan S, Wu J, Wang Y . Loss of Tight Junction Protein Claudin 18 Promotes Progressive Neoplasia Development in Mouse Stomach. Gastroenterology. 2018; 155(6):1852-1867. PMC: 6613545. DOI: 10.1053/j.gastro.2018.08.041. View

20.

Taha M, Aldirawi M, Marz S, Seebach J, Odenthal-Schnittler M, Bondareva O . EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin. Cell Rep. 2019; 29(4):1010-1026.e6. DOI: 10.1016/j.celrep.2019.09.043. View