Browse > Article
http://dx.doi.org/10.5230/jgc.2017.17.e41

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer  

Son, Myoung Won (Department of Surgery, Soonchunhyang University Cheonan Hospita)
Song, Geum Jong (Department of Surgery, Soonchunhyang University Cheonan Hospita)
Jang, Si-Hyong (Department of Pathology, Soonchunhyang University Cheonan Hospital)
Hong, Soon Auck (Department of Pathology, Soonchunhyang University Cheonan Hospital)
Oh, Mee-Hye (Department of Pathology, Soonchunhyang University Cheonan Hospital)
Lee, Ji-Hye (Department of Pathology, Soonchunhyang University Cheonan Hospital)
Baek, Moo Jun (Department of Surgery, Soonchunhyang University Cheonan Hospita)
Lee, Moon Soo (Department of Surgery, Soonchunhyang University Cheonan Hospita)
Publication Information
Journal of Gastric Cancer / v.17, no.4, 2017 , pp. 363-373 More about this Journal
Abstract
Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (${\geq}65$, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.
Keywords
Stomach neoplasms; Tumor suppressor genes; LATS1 protein, human; LATS2 protein, human;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Zhao B, Li L, Lei Q, Guan KL. The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Genes Dev 2010;24:862-874.   DOI
2 Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 2007;21:2747-2761.   DOI
3 Zhou D, Conrad C, Xia F, Park JS, Payer B, Yin Y, et al. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 2009;16:425-438.   DOI
4 Xia H, Qi H, Li Y, Pei J, Barton J, Blackstad M, et al. LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene 2002;21:1233-1241.   DOI
5 Zeng Q, Hong W. The emerging role of the hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals. Cancer Cell 2008;13:188-192.   DOI
6 Zhou Y, Tao F, Cheng Y, Xu F, Yao F, Feng D, et al. Up-regulation of ITCH is associated with down-regulation of LATS1 during tumorigenesis and progression of cervical squamous cell carcinoma. Clin Invest Med 2014;37:E384-E394.   DOI
7 Morinaga N, Shitara Y, Yanagita Y, Koida T, Kimura M, Asao T, et al. Molecular analysis of the h-warts/LATS1 gene in human breast cancer. Int J Oncol 2000;17:1125-1129.
8 Li H, Wolfe A, Septer S, Edwards G, Zhong X, Abdulkarim AB, et al. Deregulation of Hippo kinase signalling in human hepatic malignancies. Liver Int 2012;32:38-47.   DOI
9 Xu ZP, Zhu JS, Zhang Q, Wang XY. A breakdown of the Hippo pathway in gastric cancer. Hepatogastroenterology 2011;58:1611-1617.
10 Kim KJ, Jung HY, Oh MH, Cho H, Lee JH, Lee HJ, et al. Loss of ARID1A expression in gastric cancer: correlation with mismatch repair deficiency and clinicopathologic features. J Gastric Cancer 2015;15:201-208.   DOI
11 Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MA, Chen W, et al. Human homologue of the Drosophila melanogaster lats tumour suppressor modulates CDC2 activity. Nat Genet 1999;21:177-181.   DOI
12 Yabuta N, Fujii T, Copeland NG, Gilbert DJ, Jenkins NA, Nishiguchi H, et al. Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics 2000;63:263-270.   DOI
13 Furth N, Ben-Moshe NB, Pozniak Y, Porat Z, Geiger T, Domany E, et al. Down-regulation of LATS kinases alters p53 to promote cell migration. Genes Dev 2015;29:2325-2330.   DOI
14 Powzaniuk M, McElwee-Witmer S, Vogel RL, Hayami T, Rutledge SJ, Chen F, et al. The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor. Mol Endocrinol 2004;18:2011-2023.   DOI
15 Yu T, Bachman J, Lai ZC. Evidence for a tumor suppressor role for the large tumor suppressor genes LATS1 and LATS2 in human cancer. Genetics 2013;195:1193-1196.   DOI
16 Lin XY, Zhang XP, Wu JH, Qiu XS, Wang EH. Expression of LATS1 contributes to good prognosis and can negatively regulate YAP oncoprotein in non-small-cell lung cancer. Tumour Biol 2014;35:6435-6443.   DOI
17 Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer 2009;125:666-673.   DOI
18 Bosetti C, Bertuccio P, Malvezzi M, Levi F, Chatenoud L, Negri E, et al. Cancer mortality in Europe, 2005-2009, and an overview of trends since 1980. Ann Oncol 2013;24:2657-2671.   DOI
19 Oh CM, Won YJ, Jung KW, Kong HJ, Cho H, Lee JK, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013. Cancer Res Treat 2016;48:436-450.   DOI
20 Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev 1995;9:534-546.   DOI
21 Xu T, Wang W, Zhang S, Stewart RA, Yu W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 1995;121:1053-1063.
22 Visser S, Yang X. LATS tumor suppressor: a new governor of cellular homeostasis. Cell Cycle 2010;9:3892-3903.   DOI
23 Oh HJ, Lee KK, Song SJ, Jin MS, Song MS, Lee JH, et al. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer Res 2006;66:2562-2569.   DOI