ORIGINAL ARTICLE
Clinicopathological significance of Obg-like ATPase 1 and its association with Snail in gastric cancer
1
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Submission date: 2023-01-16
Acceptance date: 2023-04-05
Publication date: 2023-04-28
Corresponding author
Juan Wang
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China
Pol J Pathol 2023;74(1):42-50
KEYWORDS
TOPICS
ABSTRACT
Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear.
In the present study, mRNA level of OLA1 in gastric cancer (GC) was detected in 2 datasets downloaded from the open Gene Expression Omnibus database and 30 cancer tissues. Immunohistochemistry was performed on GC and its association with Snail in 334 GC patients.
The results showed that OLA1 mRNA and protein were elevated in GC tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumour size, lymph-node-metastasis and tumour-nodus-metastases stage (p = 0.0146, p = 0.0037, p < 0.001, respectively).
Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (p = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and a combination of them revealed improved prognostic accuracy for GC patients. High expression of OLA1 predicts poor prognosis in GC patients and may be serviced as a novel target for GC.
In the present study, mRNA level of OLA1 in gastric cancer (GC) was detected in 2 datasets downloaded from the open Gene Expression Omnibus database and 30 cancer tissues. Immunohistochemistry was performed on GC and its association with Snail in 334 GC patients.
The results showed that OLA1 mRNA and protein were elevated in GC tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumour size, lymph-node-metastasis and tumour-nodus-metastases stage (p = 0.0146, p = 0.0037, p < 0.001, respectively).
Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (p = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and a combination of them revealed improved prognostic accuracy for GC patients. High expression of OLA1 predicts poor prognosis in GC patients and may be serviced as a novel target for GC.
REFERENCES (20)
1.
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66: 115-132.
2.
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67: 7-30.
3.
Fong ZV, Tanabe KK. The clinical management of gastric cancer in the United States, Europe, and Asia. A comprehensive and evidence-based comparison and review. Cancer Am Cancer Soc 2014; 120: 2824-2838.
4.
Leipe DD, Wolf YI, Koonin EV, Aravind L. Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol 2002; 317: 41-72.
5.
Verstraeten N, Fauvart M, Versees W, Michiels J. The universally conserved prokaryotic GTPases. Microbiol Mol Biol Rev 2011; 75: 507-542.
6.
Zhang J, Rubio V, Lieberman MW, Shi ZZ. OLA1, an Obg-like ATPase, suppresses antioxidant response via nontranscriptional mechanisms. Proc Natl Acad Sci U S A 2009; 106: 15356-15361.
7.
Sun H, Luo X, Montalbano J, et al. DOC45, a novel DNA damage-regulated nucleocytoplasmic ATPase that is overexpressed in multiple human malignancies. Mol Cancer Res 2010; 8: 57-66.
8.
Zhang JW, Rubio V, Zheng S, Shi ZZ. Knockdown of OLA1, a regulator of oxidative stress response, inhibits motility and invasion of breast cancer cells. J Zhejiang Univ Sci B 2009; 10: 796-804.
9.
Bai L, Yu Z, Zhang J, et al. OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3beta/snail/E-cadherin signaling. Oncotarget 2016; 7: 10402-10413.
10.
Liu J, Yang Q, Xiao KC, Dobleman T, Hu S, Xiao GG. Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro. BMC Mol Cell Biol 2020; 21: 65.
11.
Wang J, Zheng Z, Cao Q, Liu X, Wang Z. The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer. Res Sq 2021; 3: 362393.
12.
Liu F, He Y, Cao Q, Liu N, Zhang W. TBL1XR1 is highly expressed in gastric cancer and predicts poor prognosis. Dis Markers 2016; 2436518.
13.
Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol 2008; 14: 3792-3797.
14.
Ding Z, Liu Y, Rubio V, He J, Minze LJ, Shi Z. OLA1, a Translational regulator of p21, maintains optimal cell proliferation necessary for developmental progression. Mol Cell Biol 2016; 36: 2568-2582.
15.
Koller-Eichhorn R, Marquardt T, Gail R, et al. Human OLA1 defines an ATPase subfamily in the Obg family of GTP-binding proteins. J Biol Chem 2007; 282: 19928-19937.
16.
Huang S, Zhang C, Sun C, et al. Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma. Aging (Albany NY) 2020; 12: 3025-3041.
17.
Chen H, Song R, Wang G, et al. OLA1 regulates protein synthesis and integrated stress response by inhibiting eIF2 ternary complex formation. Sci Rep 2015; 5: 13241.
18.
Xu D, Song R, Wang G, et al. Obg-like ATPase 1 regulates global protein serine/threonine phosphorylation in cancer cells by suppressing the GSK3β-inhibitor 2-PP1 positive feedback loop. Oncotarget 2016; 7: 3427-3439.
19.
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420-1428.
20.
Liu J, Miao X, Xiao B, et al. Obg-Like ATPase 1 enhances chemoresistance of breast cancer via activation of TGF-beta/Smad axis cascades. Front Pharmacol 2020; 11: 666.
Share
RELATED ARTICLE
| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
