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International Ophthalmology
Erschienen in: International Ophthalmology 2/2020

30.09.2019 | Original Paper

CDKN2A, CDK1, and CCNE1 overexpression in sebaceous gland carcinoma of eyelid

verfasst von: Tatsuya Yunoki, Tetsushi Hirano, Yoshiaki Tabuchi, Yukihiro Furusawa, Misako Torigoe, Takahiko Nakajima, Johji Imura, Atsushi Hayashi

Erschienen in: International Ophthalmology | Ausgabe 2/2020

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Abstract

Purpose

To investigate the overexpression of genes in sebaceous gland carcinoma (SGC) of the eyelid compared to sebaceous adenoma of the eyelid in order to elucidate the molecular mechanism underlying pathogenesis.

Methods

We performed histopathological examination of eyelid tissues surgically removed from four patients diagnosed with SGC (cases 1–3) and sebaceous adenoma (case 4) of the eyelid. Next, we performed global gene expression analysis of surgical tissue samples using a GeneChip® system and the Ingenuity Pathways Knowledge Base. The results of the GeneChip® analysis were explored with quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

Results

In the SGC samples, we found that 211, 199, and 199 genes, respectively, showed ≥ 2.0-fold higher expression than those in the sebaceous adenoma sample (case 4); 194 genes were common to all three SGC samples. For the 194 genes with upregulated expression, functional category analysis showed that SGC of the eyelid employed a unique gene network, including cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 1 (CDK1), and cyclin E1 (CCNE1), which are related to cell cycle progression, incidence of tumor, and cell viability. Furthermore, qRT-PCR analysis showed that the expression levels of CDKN2A, CDK1, and CCNE1 were significantly upregulated in all SGC cases compared to those in the sebaceous adenoma case. These data were similar to the results of microarray analysis.

Conclusion

Overexpression of cell cycle-related genes CDKN2A, CDK1, CCNE1, and their gene network may help elucidate the pathogenic pathway of SGC of the eyelid at the molecular level.
Literatur
1.
Takamura H, Yamashita H (2005) Clinicopathological analysis of malignant eyelid tumor cases at Yamagata university hospital: statistical comparison of tumor incidence in Japan and in other countries. Jpn J Ophthalmol 49:349–354PubMed
2.
Shields JA, Demirci H, Marr BP, Eagle RC Jr, Shields CL (2004) Sebaceous carcinoma of the eyelids: personal experience with 60 cases. Ophthalmology 111:2151–2157PubMed
3.
Leibovitch I, Selva D, Huilgol S, Davis G, Dodd T, James CL (2006) Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen’s disease. J Cutan Pathol 33:303–308PubMed
4.
Buitrago W, Joseph AK (2008) Sebaceous carcinoma: the great masquerader: emerging concepts in diagnosis and treatment. Dermatol Ther 21:459–466PubMed
5.
Choi YJ, Jin HC, Lee MJ, Kim N, Choung HK, Khwarg SI (2014) Prognostic value of clinical and pathologic T stages defined by the American Joint Committee on Cancer for eyelid sebaceous carcinoma in Korea. Jpn J Ophthalmol 58:327–333PubMed
6.
Watanabe A, Sun MT, Pirbhai A, Ueda K, Katori N, Selva D (2013) Sebaceous carcinoma in Japanese patients: clinical presentation, staging and outcomes. Br J Ophthalmol 97:1459–1463PubMed
7.
Kaliki S, Gupta A, Ali MH, Ayyar A, Naik MN (2016) Prognosis of eyelid sebaceous gland carcinoma based on the tumor (T) category of the American Joint Committee on Cancer (AJCC) classification. Int Ophthalmol 36:681–690PubMed
8.
Esmaeli B, Nasser QJ, Cruz H, Fellman M, Warneke CL, Ivan D (2012) American Joint Committee on Cancer T category for eyelid sebaceous carcinoma correlates with nodal metastasis and survival. Ophthalmology 119:1078–1082PubMed
9.
Kaliki S, Ayyar A, Dave TV, Ali MJ, Mishra DK, Naik MN (2015) Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians. Eye (Lond) 29:958–963
10.
Mulay K, Aggarwal E, White VA (2013) Periocular sebaceous gland carcinoma: a comprehensive review. Saudi J Ophthalmol 27:159–165PubMedPubMedCentral
11.
Chao AN, Shields CL, Krema H, Shields JA (2001) Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology 108:1877–1883PubMed
12.
Bell WR, Singh K, Rajan KdA, Eberhart CG (2015) Expression of p16 and p53 in intraepithelial periocular sebaceous carcinoma. Ocul Oncol Pathol 2:71–75PubMedPubMedCentral
13.
Kiyosaki K, Nakada C, Hijiya N, Tsukamoto Y, Matsuura K, Nakatsuka K, Daa T, Yokoyama S, Imaizumi M, Moriyama M (2010) Analysis of p53 mutations and the expression of p53 and p21WAF1/CIP1 protein in 15 cases of sebaceous carcinoma of the eyelid. Invest Ophthalmol Vis Sci 51:7–11PubMed
14.
Liau JY, Liao SL, Hsiao CH, Lin MC, Chang HC, Kuo KT (2014) Hypermethylation of the CDKN2A gene promoter is a frequent epigenetic change in periocular sebaceous carcinoma and is associated with younger patient age. Hum Pathol 45:533–539PubMed
15.
Bhardwaj M, Sen S, Sharma A, Kashyap S, Chosdol K, Pushker N, Bajaj MS, Bakhshi S (2015) ZEB2/SIP1 as novel prognostic indicator in eyelid sebaceous gland carcinoma. Hum Pathol 46:1437–1442PubMed
16.
Lee MJ, Kim N, Choung HK, Choe JY, Khwarg SI, Kim JE (2016) Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target. J Cancer Res Clin Oncol 142:125–133PubMed
17.
Kim N, Choung HK, Lee MJ, Khwarg SI, Kim JE (2015) Cancer stem cell markers in eyelid sebaceous gland carcinoma: high expression of ALDH1, CD133, and ABCG2 correlates with poor prognosis. Invest Ophthalmol Vis Sci 56:1813–1819PubMed
18.
Yunoki T, Tabuchi Y, Hayashi A (2017) Expression of anti-apoptotic protein BAG3 in human sebaceous gland carcinoma of the eyelid. Anticancer Res 37:1931–1934PubMed
19.
Gil da Costa RM, Rema A, Payo-Puente P, Gärtner F (2007) Immunohistochemical characterization of a sebaceous gland carcinoma in a gerbil (Meriones unguiculatus). J Comp Pathol 137:130–132PubMed
20.
Jayaraj P, Sen S, Dhanaraj PS, Jhajhria R, Singh S, Singh VK (2017) Immunohistochemical expression of X-linked inhibitor of apoptosis in eyelid sebaceous gland carcinoma predicts a worse prognosis. Indian J Ophthalmol 65:1109–1113PubMedPubMedCentral
21.
Erovic BM, Al Habeeb A, Harris L, Goldstein DP, Kim D, Ghazarian D, Irish JC (2013) Identification of novel target proteins in sebaceous gland carcinoma. Head Neck 35:642–648PubMed
22.
Husain A, Blumenschein G, Esmaeli B (2008) Treatment and outcomes for metastatic sebaceous cell carcinoma of the eyelid. Int J Dermatol 47:276–279PubMed
23.
Joshi P, Joshi A, Norohna V, Prabhash K, Kane S, D’cruz AK (2012) Sebaceous carcinoma and systemic chemotherapy. Indian J Med Paediatr Oncol 33:239–241PubMedPubMedCentral
24.
Orcurto A, Gay BE, Sozzi WJ, Gilliet M, Leyvraz S (2014) Long-term remission of an aggressive sebaceous carcinoma following chemotherapy. Case Rep Dermatol 6:80–84PubMedPubMedCentral
25.
Tabuchi Y, Yunoki T, Hoshi N, Suzuki N, Kondo T (2014) Genes and gene networks involved in sodium fluoride-elicited cell death accompanying endoplasmic reticulum stress in oral epithelial cells. Int J Mol Sci 15:8959–8978PubMedPubMedCentral
26.
Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell cycle control causing specific inhibition of cyclin D-CDK4. Nature 366:704–707PubMed
27.
Hara E, Smith R, Parry D, Tahara H, Stone S, Peters G (1996) Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol Cell Biol 16:859–867PubMedPubMedCentral
28.
Kataoka M, Wiehle S, Spitz F, Schumacher G, Roth JA, Cristiano RJ (2000) Down-regulation of bcl-2 is associated with p16INK4-mediated apoptosis in non-small cell lung cancer cells. Oncogene 19:1589–1595PubMed
29.
Urashima M, DeCaprio JA, Chauhan D, Teoh G, Ogata A, Treon SP, Hoshi Y, Anderson KC (1997) p16INK4A promotes differentiation and inhibits apoptosis of JKB acute lymphoblastic leukemia cells. Blood 90:4106–4115PubMed
30.
Shapiro GI, Edwards CD, Ewen ME, Rollins BJ (1998) p16INK4A participates in a G1 arrest checkpoint in response to DNA damage. Mol Cell Biol 18:378–387PubMedPubMedCentral
31.
32.
Ohtani N, Yamakoshi K, Takahashi A, Hara E (2004) The p16INK4a-RB pathway: molecular link between cellular senescence and tumor suppression. J Med Invest 51:146–153PubMed
33.
Stagner AM, Afrogheh AH, Jakobiec FA, Iacob CE, Grossniklaus HE, Deshpande V, Maske C, Hiss DC, Faquin WC (2016) p16 expression is not a surrogate marker for high-risk human papillomavirus infection in periocular sebaceous carcinoma. Am J Ophthalmol 170:168–175PubMed
34.
Kwon MJ, Shin HS, Nam ES, Cho SJ, Lee MJ, Lee S, Park HR (2015) Comparison of HER2 gene amplification and KRAS alteration in eyelid sebaceous carcinomas with that in other eyelid tumors. Pathol Res Pract 211:349–355PubMed
35.
Huang WW, Ko SW, Tsai HY, Chung JG, Chiang JH, Chen KT, Chen YC, Chen HY, Chen YF, Yang JS (2011) Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways. Int J Oncol 38:1067–1073PubMed
36.
Xi Q, Huang M, Wang Y, Zhong J, Liu R, Xu G, Jiang L, Wang J, Fang Z, Yang S (2015) The expression of CDK1 is associated with proliferation and can be a prognostic factor in epithelial ovarian cancer. Tumour Biol 36:4939–4948PubMed
37.
Hongo F, Takaha N, Oishi M, Ueda T, Nakamura T, Naitoh Y, Naya Y, Kamoi K, Okihara K, Matsushima T, Nakayama S, Ishihara H, Sakai T, Miki T (2014) CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence. Urol Oncol 32:1240–1246PubMed
38.
Gan W, Zhao H, Li T, Liu K, Huang J (2017) CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget 8:71618–71629PubMedPubMedCentral
39.
Kim SJ, Masuda N, Tsukamoto F, Inaji H, Akiyama F, Sonoo H, Kurebayashi J, Yoshidome K, Tsujimoto M, Takei H, Masuda S, Nakamura S, Noguchi S (2014) The cell cycle profiling-risk score based on CDK1 and 2 predicts early recurrence in node-negative, hormone receptor-positive breast cancer treated with endocrine therapy. Cancer Lett 355:217–223PubMed
40.
Zhang X, Hu S, Zhang X, Wang L, Zhang X, Yan B, Zhao J, Yang A, Zhang R (2014) MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 443:1078–1084PubMed
41.
Coverley D, Laman H, Laskey RA (2002) Distinct roles for cyclins E and A during DNA replication complex assembly and activation. Nat Cell Biol 4:523–528PubMed
42.
Nakayama N, Nakayama K, Shamima Y, Ishikawa M, Katagiri A, Iida K, Miyazaki K (2010) Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer 116:2621–2634PubMed
43.
Jung YJ, Lee KH, Choi DW, Han CJ, Jeong SH, Kim KC, Oh JW, Park TK, Kim CM (2001) Reciprocal expressions of cyclin E and cyclin D1 in hepatocellular carcinoma. Cancer Lett 168:57–63PubMed
44.
Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhsng CZ, Wala J, Mermel CH, Sougnez C, Gabriel SB, Hernandez B, Shen H, Laird PW, Getz G, Meyerson M, Beroukhim R (2013) Pan-cancer patterns of somatic copy number alteration. Nat Genet 45:1134–1140PubMedPubMedCentral
45.
Sung WK, Zheng H, Li S, Chen R, Liu X, Li Y, Lee NP, Lee WH, Ariyaratne PN, Tennakoon C, Mulawadi FH, Wong KF, Liu AM, Poon RT, Fan ST, Chan KL, Gong Z, Hu Y, Lin Z, Wang G, Zhang Q, Barber TD, Chou WC, Aggarwal A, Hao K, Zhou W, Zhang C, Hardwick J, Buser C, Xu J, Kan Z, Dai H, Mao M, Reinhard C, Wang J, Luk JM (2012) Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet 44:765–769PubMed
46.
Bagheri-Yarmand R, Nanos-Webb A, Biernacka A, Bui T, Keyomarsi K (2010) Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. Cancer Res 70:5085–5095PubMedPubMedCentral
47.
Normand G, Hemmati PG, Verdoodt B, von Haefen C, Wendt J, Güner D, May E, Dörken B, Daniel PT (2005) p14ARF induces G2 cell cycle arrest in p53- and p21-deficient cells by down-regulating p34cdc2 kinase activity. J Biol Chem 280:7118–7130PubMed
48.
Eymin B, Leduc C, Coll JL, Brambilla E, Gazzeri S (2003) p14ARF induces G2 arrest and apoptosis independently of p53 leading to regression of tumours established in nude mice. Oncogene 22:1822–1835PubMed
49.
Chien WW, Domenech C, Catallo R, Kaddar T, Magaud JP, Salles G, Ffrench M (2011) Cyclin-dependent kinase 1 expression is inhibited by p16(INK4a) at the post-transcriptional level through the microRNA pathway. Oncogene 30:1880–1891PubMed
50.
Vernell R, Helin K, Müller H (2003) Identification of target genes of the p16INK4A-pRB-E2F pathway. J Biol Chem 278:46124–46137PubMed
51.
Okajima E, Fukuda T, Okita S, Tsutsumi M, Hirao Y, Okajima E, Konishi Y (1996) Infrequent somatic alteration of p16/MTS1 in human primary superficial bladder cancers. Cancer Lett 103:227–231PubMed
Metadaten
Titel
CDKN2A, CDK1, and CCNE1 overexpression in sebaceous gland carcinoma of eyelid
verfasst von
Tatsuya Yunoki
Tetsushi Hirano
Yoshiaki Tabuchi
Yukihiro Furusawa
Misako Torigoe
Takahiko Nakajima
Johji Imura
Atsushi Hayashi
Publikationsdatum
30.09.2019
Verlag
Springer Netherlands
Erschienen in
International Ophthalmology / Ausgabe 2/2020
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-019-01185-7

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