Abstract
Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan–Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan–Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013–7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients.
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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107
Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316. doi:10.1016/j.oraloncology.2008.06.002
Neville BW, Day TA (2002) Oral cancer and precancerous lesions. CA Cancer J Clin 52(4):195–215
Silverman S Jr (2001) Demographics and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc 132(Suppl):7S–11S
Mahfouz ME, Rodrigo JP, Takes RP, Elsheikh MN, Rinaldo A, Brakenhoff RH, Ferlito A (2010) Current potential and limitations of molecular diagnostic methods in head and neck cancer. Eur Arch Otorhinolaryngol 267(6):851–860. doi:10.1007/s00405-009-1177-3
Grimminger CM, Danenberg PV (2011) Update of prognostic and predictive biomarkers in oropharyngeal squamous cell carcinoma: a review. Eur Arch Otorhinolaryngol 268(1):5–16. doi:10.1007/s00405-010-1369-x
Hunt JL, Barnes L, Lewis JS Jr, Mahfouz ME, Slootweg PJ, Thompson LD, Cardesa A, Devaney KO, Gnepp DR, Westra WH, Rodrigo JP, Woolgar JA, Rinaldo A, Triantafyllou A, Takes RP, Ferlito A (2014) Molecular diagnostic alterations in squamous cell carcinoma of the head and neck and potential diagnostic applications. Eur Arch Otorhinolaryngol 271(2):211–223. doi:10.1007/s00405-013-2400-9
Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, Pathmanathan R, Prime SS, Teo SH, Patel V, Gutkind JS (2009) Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure. Oral Oncol 45(8):712–719. doi:10.1016/j.oraloncology.2008.11.002
Routray S (2014) Caveolin-1 in oral squamous cell carcinoma microenvironment: an overview. Tumour biol J Int Soc Oncodevelop Biol Med. doi:10.1007/s13277-014-2482-z
Kumagai K, Nimura Y, Mizota A, Miyahara N, Aoki M, Furusawa Y, Takiguchi M, Yamamoto S, Seki N (2006) Arpc1b gene is a candidate prediction marker for choroidal malignant melanomas sensitive to radiotherapy. Invest Ophthalmol Vis Sci 47(6):2300–2304. doi:10.1167/iovs.05-0810
Kaneda A, Kaminishi M, Nakanishi Y, Sugimura T, Ushijima T (2002) Reduced expression of the insulin-induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers. Int J Cancer J Int du Cancer 100(1):57–62. doi:10.1002/ijc.10464
Staubach S, Hanisch FG (2011) Lipid rafts: signaling and sorting platforms of cells and their roles in cancer. Expert Rev Prot 8(2):263–277. doi:10.1586/epr.11.2
Williams TM, Lisanti MP (2005) Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 288(3):C494–C506. doi:10.1152/ajpcell.00458.2004
Hung KF, Lin SC, Liu CJ, Chang CS, Chang KW, Kao SY (2003) The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis. J Oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol 32(8):461–467
Nohata N, Hanazawa T, Kikkawa N, Mutallip M, Fujimura L, Yoshino H, Kawakami K, Chiyomaru T, Enokida H, Nakagawa M, Okamoto Y, Seki N (2011) Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma. Int J Oncol 38(1):209–217
Zhang H, Su L, Muller S, Tighiouart M, Xu Z, Zhang X, Shin HJ, Hunt J, Sun SY, Shin DM, Chen ZG (2008) Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma. Br J Cancer 99(10):1684–1694. doi:10.1038/sj.bjc.6604735
Welch MD, DePace AH, Verma S, Iwamatsu A, Mitchison TJ (1997) The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J Cell Biol 138(2):375–384
Molli PR, Li DQ, Bagheri-Yarmand R, Pakala SB, Katayama H, Sen S, Iyer J, Chernoff J, Tsai MY, Nair SS, Kumar R (2010) Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A. J Cell Biol 190(1):101–114. doi:10.1083/jcb.200908050
Zain RB, Athirajan V, Ghani WM, Razak IA, Raja Latifah RJ, Ismail SM, Sallam AA, Bustam AZ, Rahman ZA, Hussien A, Talib N, Cheong SC, Jallaludin A (2013) An oral cancer biobank initiative: a platform for multidisciplinary research in a developing country. Cell Tissue Banking 14(1):45–52. doi:10.1007/s10561-012-9298-0
Sobin LH, Gospodarowicz MK, Wittekind C (2011) TNM classification of malignant tumours. Wiley
Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, Siow MY, Kallarakkal TG, Ramanathan A, Yang Y-H, Khor GH, Rahman ZAA, Ismail SM, Prepageran N, Wan Mustafa WM, Abraham MT, Tay KK, Cheong SC, Zain RB (2014) Overexpression of MMP13 Is Associated with Clinical Outcomes and Poor Prognosis in Oral Squamous Cell Carcinoma. Sci World J 2014:12. doi:10.1155/2014/897523
Kunzel J, Psychogios G, Mantsopoulos K, Grundtner P, Waldfahrer F, Iro H (2014) Lymph node ratio as a predictor of outcome in patients with oropharyngeal cancer. Eur Arch Otorhinolaryngol 271(5):1171–1180. doi:10.1007/s00405-013-2513-1
Mesquita JA, Queiroz LM, Silveira EJ, Gordon-Nunez MA, Godoy GP, Nonaka CF, Alves PM (2015) Association of immunoexpression of the galectins-3 and -7 with histopathological and clinical parameters in oral squamous cell carcinoma in young patients. Eur Arch Otorhinolaryngol. doi:10.1007/s00405-014-3439-y
Anicin A, Gale N, Smid L, Kos J, Strojan P (2013) Expression of stefin A is of prognostic significance in squamous cell carcinoma of the head and neck. Eur Arch Otorhinolaryngol 270(12):3143–3151. doi:10.1007/s00405-013-2465-5
Choi HG, Kim JS, Kim KH, Sung MW, Choe JY, Kim JE, Jung YH (2015) Expression of hypoxic signaling markers in head and neck squamous cell carcinoma and its clinical significance. Eur Arch Otorhinolaryngol 272(1):219–228. doi:10.1007/s00405-014-2954-1
Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, Zain RB, Lau SH, Cheong SC (2013) Four-protein signature accurately predicts lymph node metastasis and survival in oral squamous cell carcinoma. Hum Pathol 44(3):417–426. doi:10.1016/j.humpath.2012.06.007
Xue J, Chen H, Diao L, Chen X, Xia D (2010) Expression of caveolin-1 in tongue squamous cell carcinoma by quantum dots. Euro J Histochem EJH 54(2):e20
Han SE, Park KH, Lee G, Huh YJ, Min BM (2004) Mutation and aberrant expression of Caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines. Int J Oncol 24(2):435–440
Goetz JG, Lajoie P, Wiseman SM, Nabi IR (2008) Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metast Rev 27(4):715–735. doi:10.1007/s10555-008-9160-9
Chorev DS, Moscovitz O, Geiger B, Sharon M (2014) Regulation of focal adhesion formation by a vinculin-Arp2/3 hybrid complex. Nature Comm 5:3758. doi:10.1038/ncomms4758
Zucchini C, Rocchi A, Manara MC, De Sanctis P, Capanni C, Bianchini M, Carinci P, Scotlandi K, Valvassori L (2008) Apoptotic genes as potential markers of metastatic phenotype in human osteosarcoma cell lines. Int J Oncol 32(1):17–31
Acknowledgement
This study was supported by University of Malaya Research Grant (RP002E-13HTM) and University of Malaya Postgraduate Research Fund (PPPC/C1-2012/DEGC/24). The authors acknowledged the Oral Cancer Research and Coordinating Centre (OCRCC), University of Malaya (UM) for providing tissue and data from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). The authors also thanked the clinicians and pathologists from Ministry of Health Malaysia for their clinical and pathologic expertise.
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Auzair, L.B.M., Vincent-Chong, V.K., Ghani, W.M.N. et al. Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC). Eur Arch Otorhinolaryngol 273, 1885–1893 (2016). https://doi.org/10.1007/s00405-015-3703-9
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DOI: https://doi.org/10.1007/s00405-015-3703-9