Evaluation of LRIG1 Expression in Larynx Pathologies

Year 2022, Volume: 32 Issue: 2, 31 - 36, 11.05.2022

Yavuz Gündoğdu , Orhan Asya Ayşegül Gönen Tajaddin Muradov Selim Yiğit Erçetin Zeliha Leyla Cinel Ali Cemal Yumuşakhuylu

https://doi.org/10.26650/Tr-ENT.2022.1077135

Abstract

Objective: Studies have been performed on many biomolecules to determine the prognosis of LSCC and predict the course of the disease. However, a molecular marker that can be used clinically has not yet been found. Therefore, in this study, we aimed to investigate the expression levels of LRIG 1 in laryngeal cancer.

Materials and Methods: In our study, 219 cases who underwent surgery due to LSCC and 88 randomly selected patients whose pathologic result were benign and premalignant lesions in Marmara University Pendik Education and Research Hospital between 2003 and 2018 were analyzed. Patients’ data were obtained from the medical records. The tissue microarray method was used to evaluate specimens.

Results: There was a statistically significant difference between the tumor differentiation, diagnosis, and the expression of LRIG1 (respectively p=0.045, p<0.001). Also, an increase in the degree of dysplasia in premalignant lesions correlates with a decrease in LRIG1 expression (p=0.015).

Conclusion: Our findings suggest that LRIG1 plays a role in the early tumorigenesis of LSCC. Therefore, LRIG1 can be a target molecule for treatment approaches. However, LRIG1 was not correlated with overall survival of the LSCC.

Keywords

LRIG1, Laryngeal carcinoma, tumorigenesis

Supporting Institution

Marmara University BAPKO

Project Number

SAG -C- TUP -120417-0157

References

• 1. Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975-2018, National Cancer Institute. Bethesda, MD. 2018. https://seer.cancer.gov/statfacts/ html/laryn.html (Accession date: 25.04.2022 ) google scholar
• 2. Nocini R, Molteni G, Mattiuzzi C, Lippi G. Updates on larynx cancer epidemiology. Chin J Cancer Res 2020;32(1):18. google scholar
• 3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71(3):209-49. google scholar
• 4. Pruess M, Fleischmann W, Kanapin A, Karavidopoulou Y, Kersey P, Kriventseva E, et al. The Proteome Analysis database: a tool for the in silico analysis of whole proteomes. Nucleic Acids Research 2003;31(1):414-7. google scholar
• 5. Kobe B, Kajava AV. The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 2001;11(6):725-32. google scholar
• 6. Nilsson J, Vallbo C, Guo D, Golovleva I, Hallberg B, Henriksson R, et al. Cloning, characterization, and expression of human LIG1. Biochem Biophys Res Commun 2001;284(5):1155-61. google scholar
• 7. Hedman Hk, Nilsson J, Guo D, Henriksson R. Is LRIG1 a tumour suppressor gene at chromosome 3p14.3? Acta Oncol 2002;41(4):352-4. google scholar
• 8. Jensen KB, Watt FM. Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. PNAS 2006;103(32):11958-63. google scholar
• 9. Tanemura A, Nagasawa T, Inui S, Itami S. LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases. Dermatol Surg 2005;31(4):423-30. google scholar
• 10. Thomasson M, Wang B, Hammarsten P, Dahlman A, Persson JL, Josefsson A, et al. LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer. Int J Cancer 2011;128(12):2843-52. google scholar
• 11. Guo D, Nilsson J, Haapasalo H, Raheem O, Bergenheim T, Hedman H, et al. Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. Acta Neuropathol 2006;111(3):238-46. google scholar
• 12. Lindquist D, Kvarnbrink S, Henriksson R, Hedman H. LRIG and cancer prognosis. Acta Oncol 2014;53(9):1135-42. google scholar
• 13. Suzuki Y, Sato N, Tohyama M, Wanaka A, Takagi T. cDNA cloning of a novel membrane glycoprotein that is expressed specifically in glial cells in the mouse brain: LIG-1, a protein with leucine-rich repeats and immunoglobulin-like domains. J Biol Chem 1996;271(37):22522-7. google scholar
• 14. Yi W, Holmlund C, Nilsson J, Inui S, Lei T, Itami S, et al. Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. Exp Cell Res 2011;317(4):504-12. google scholar
• 15. Shattuck DL, Miller JK, Laederich M, Funes M, Petersen H, Carraway III KL, et al. LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2 synergy. Mol Cell Biol 2007;27(5):1934-46. google scholar
• 16. Ledda F, Bieraugel O, Fard SS, Vilar M, Paratcha G. Lrig1 is an endogenous inhibitor of Ret receptor tyrosine kinase activation, downstream signaling, and biological responses to GDNF. J Neurosci 2008;28(1):39-49. google scholar
• 17. Jensen KB, Collins CA, Nascimento E, Tan DW, Frye M, Itami S, et al. Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell 2009;4(5):427-39. google scholar
• 18. Lu L, Teixeira VH, Yuan Z, Graham TA, Endesfelder D, Kolluri K, et al. LRIG1 regulates cadherin-dependent contact inhibition directing epithelial homeostasis and pre-invasive squamous cell carcinoma development. J Pathol 2013;229(4):608-20. google scholar
• 19. Jensen KB, Jones J, Watt FM. A stem cell gene expression profile of human squamous cell carcinomas. Cancer Letters 2008;272(1):23-31. google scholar
• 20. Muller S, Lindquist D, Kanter L, Flores-Staino C, Henriksson R, Hedman H, et al. Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma. Int J Oncol 2013;42(1):247-52. google scholar
• 21. Krig SR, Frietze S, Simion C, Miller JK, Fry WH, Rafidi H, et al. Lrig1 is an estrogen-regulated growth suppressor and correlates with longer relapse-free survival in ERa-positive breast cancer. Mol Cancer Res 2011;9(10):1406-17. google scholar
• 22. Lindquist D, Nasman A, Tarjan M, Henriksson R, Tot T, Dalianis T, et al. Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer. Br J Cancer 2014;110(7):1793-800. google scholar
• 23. Ranhem C, Lillsunde Larsson G, Hedman H, Lindquist D, Karlsson MG, Hellström A-C, et al. Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma. PLoS One 2017;12(8):e0183816. doi: 10.1371/journal.pone.0183816 google scholar
• 24. Li F, Ye Z-Q, Guo D-S, Yang W-M. Suppression of bladder cancer cell tumorigenicity in an athymic mouse model by adenoviral vector-mediated transfer of LRIG1. Oncol Rep 2011;26(2):439-46. google scholar
• 25. Johansson M, Oudin A, Tiemann K, Bernard A, Golebiewska A, Keunen O, et al. The soluble form of the tumor suppressor Lrig1 potently inhibits in vivo glioma growth irrespective of EGF receptor status. Neuro Oncol 2013;15(9):1200-11. google scholar
• 26. Stutz MA, Shattuck D, Laederich M, Carraway KL, Sweeney C. LRIG1 negatively regulates the oncogenic EGF receptor mutant EGFRvIII. Oncogene 2008;27(43):5741-52. google scholar
• 27. Li F, Yang W, Guo D, Hu Z, Xu H, Ye Z. LRIG1 combined with cisplatin enhances bladder cancer lesions via a novel pathway. Oncol Rep 2011;25(6):1629-37. google scholar