ORIGINAL ARTICLE
Clinical significance of nuclear localisation of agrin in lung adenocarcinoma
1
Department of Thoracic Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, China
Submission date: 2018-11-22
Final revision date: 2019-04-14
Acceptance date: 2019-05-26
Publication date: 2019-12-08
Pol J Pathol 2019;70(3):198-204
KEYWORDS
TOPICS
ABSTRACT
Agrin has recently been identified as a novel oncogene that is overexpressed in several types of human cancers. However, its role in lung cancer has not yet been investigated. The purpose of the current study was to investigate agrin protein expression in lung cancer and evaluate its clinicopathological and prognostic significance. In this study, A total of 86 lung adenocarcinoma samples paired with adjacent non-tumour tissue samples and eight lung adenocarcinoma non-paired samples were selected for immunohistochemical staining for agrin. Strong staining of agrin in nuclei of lung adenocarcinoma tissues was observed, but not in the nuclei of normal lung tissues (p < 0.001). Consistent with staining in lung adenocarcinoma tissues, the nuclei staining of agrin was also detected in lung cancer cell lines by immunofluorescence. This is the first report demonstrating that agrin is highly expressed in nuclei of lung adenocarcinoma tissues and that it is strongly correlated with lymph node metastasis (p = 0.002), clinical stage (p = 0.024), and poor differentiation (p = 0.022). Agrin-positive nuclear staining of lung adenocarcinoma cells could be used to identify greatly increased risk of metastasis in patients after surgery, which might serve as a valuable prognostic marker.
REFERENCES (26)
1.
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67: 7-30.
2.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
3.
Yang L, Fan JH, Liu LL, et al. Comparison of gefitinib and platinum-based chemotherapy and only platinum-based chemotherapy to treat lung adenocarcinoma. J Biol Regul Homeost Agents 2018; 32: 613-618.
4.
Cooper WA, Lam DC, O’Toole SA, et al. Molecular biology of lung cancer. J Thorac Dis 2013; 5 Suppl 5: S479-S490.
5.
Zheng LJ, Yang D, Sun LJ, et al. Different molecular subtypes of breast invasive ductal carcinoma. J Biol Regul Homeost Agents 2018; 32: 553-563.
6.
Xia Y, Xiong N, Huang Y. Relationship between methylation status of RASSF2A gene promoter and endometriosis-associated ovarian cancer. J Biol Regul Homeost Agents 2018; 32: 21-28.
7.
Ettinger DS, Akerley W, Bepler G, et al. Non-small cell lung cancer. J Natl Compr Canc Netw 2010; 8: 740-801.
8.
Kim N, Stiegler AL, Cameron TO, et al. Lrp4 is a receptor for Agrin and forms a complex with MuSK. Cell 2008; 135: 334-342.
9.
Zhang B, Luo S, Wang Q, et al. Lrp4 serves as a coreceptor of Agrin. Neuron 2008; 60: 285-297.
10.
Gautam M, Noakes PG, Moscoso L, et al. Defective neuromuscular synaptogenesis in Agrin-deficient mutant mice. Cell 1996; 85: 525-535.
11.
Batmunkh E, Tátrai P, Szabó E, et al. Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 2007; 38: 1508-1515.
12.
Klein-Scory S, Kübler S, Diehl H, et al. Immunoscreening of the extracellular proteome of colorectal cancer cells. BMC Cancer 2010; 10: 70.
13.
Kawahara R, Granato DC, Carnielli CM, et al. Agrin and perlecan mediate tumorigenic processes in oral squamous cell carcinoma. PLoS One 2014; 9: e115004.
14.
Rivera C, Zandonadi FS, Sánchez-Romero C, et al. Agrin has a pathological role in the progression of oral cancer. Br J Cancer 2018; 118: 1628-1638.
15.
Chakraborty S, Lakshmanan M, Swa HL, et al. An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nature communications 2015; 6: 6184.
16.
Chakraborty S, Njah K, Pobbati AV, et al. Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway. Cell Rep 2017; 18: 2464-2479.
17.
Neill T, Schaefer L, Iozzo RV. Decoding the matrix: instructive roles of proteoglycan receptors. Biochemistry 2015; 54: 4583-4598.
18.
Scherbakov N, Knops M, Ebner N, et al. Evaluation of C-terminal Agrin fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation. J Cachex Sarcopenia Muscle 2016; 7: 60-67.
19.
Casaletto JB, McClatchey AI. Spatial regulation of receptor tyrosine kinases in development and cancer. Nat Rev Cancer 2012; 12: 387-400.
20.
Mertani HC, Garcia-Caballero T, Lambert A, et al. Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int J Cancer 1998; 79: 202-211.
21.
Lincoln DT, Kaiser HE, Raju GP, et al. Growth hormone and colorectal carcinoma: localization of receptors. In Vivo 2000; 14: 41-49.
22.
García-Caballero T, Mertani HM, Lambert A, et al. Increased expression of growth hormone and prolactin receptors in hepatocellular carcinomas. Endocrine 2000; 12: 265-271.
23.
Lincoln DT, Sinowatz F, Kolle S, et al. Up-regulation of growth hormone receptor immunoreactivity in human melanoma. Anticancer Res 1999; 19: 1919-1931.
24.
Brooks AJ, Gordon D, Brown RJ, et al. Nuclear targeting of the growth hormone receptor results in dysregulation of cell proliferation and tumorigenesis. Proc Natl Acad Sci 2007; 104: 13331-13336.
25.
Brooks AJ, Waters MJ. The growth hormone receptor: mechanism of activation and clinical implications. Nat Rev Endocrinol 2010; 6: 515-525.
26.
Krolewski JJ. Cytokine and growth factor receptors in the nucleus: what’s up with that? J Cell Biochem 2005; 95: 478-487.
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.
