Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development

Iwaya,Takeshi; Sawada,Genta; Amano,Suburu; Kume,Kohei; Ito,Chie; Endo,Fumitaka; Konosu,Masafumi; Shioi,Yoshihiro; Akiyama,Yuji; Takahara,Takeshi; Otsuka,Koki; Nitta,Hiroyuki; Koeda,Keisuke; Mizuno,Masaru; Nishizuka,Satoshi; Sasaki,Akira; Mimori,Koshi

doi:10.3892/ijo.2016.3817

Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development

Authors:
- Takeshi Iwaya
- Genta Sawada
- Suburu Amano
- Kohei Kume
- Chie Ito
- Fumitaka Endo
- Masafumi Konosu
- Yoshihiro Shioi
- Yuji Akiyama
- Takeshi Takahara
- Koki Otsuka
- Hiroyuki Nitta
- Keisuke Koeda
- Masaru Mizuno
- Satoshi Nishizuka
- Akira Sasaki
- Koshi Mimori
View Affiliations

Affiliations: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka, University, Suita 565-0871, Japan, Department of Surgery, Kyushu University Beppu Hospital, Beppu 874-0838, Japan
Published online on: December 22, 2016 https://doi.org/10.3892/ijo.2016.3817
Pages: 441-447

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tylosis is an inherited disorder characterized by abnormal palmoplantar skin thickening and a highly elevated risk of esophageal squamous cell carcinoma (ESCC). Analyses of tylosis in families have localized the responsible gene locus to a region of chromosome 17q25.1. Frequent loss of heterozygosity (LOH) in 17q25.1 was also observed in the sporadic form of ESCC. A putative tumor suppressor gene for ESCC may exist at this locus. We investigated the expression patterns of genes on 17q25.1 in tumor and corresponding normal tissues from patients with sporadic ESCC using RNA sequence analysis. For candidate genes, quantitative real-time reverse transcription-PCR (qRT-PCR), direct sequence, LOH and methylation analyses were performed using 93 clinical ESCC samples and 10 cell lines. A significant downregulation of ST6GALNAC1 was demonstrated in ESCC tissues compared to its expression in normal tissues by qRT-PCR (n=93, p<0.0001). Frequent LOH (17/27, 62.9%) and hyper‑methylation in ST6GALNAC1 were also observed in all cell lines. Our results indicated that ST6GALNAC1 was downregulated in sporadic ESCC via hyper-methylation and LOH, and it may be a candidate responsible gene for ESCC. Furthermore, recent studies suggest that multiple genes on chromosome 17q25 are involved in ESCC development.

View Figures

View References

1	Ellis A, Field JK, Field EA, Friedmann PS, Fryer A, Howard P, Leigh IM, Risk J, Shaw JM and Whittaker J: Tylosis associated with carcinoma of the oesophagus and oral leukoplakia in a large Liverpool family - a review of six generations. Eur J Cancer B Oral Oncol. 30B:102–112. 1994. View Article : Google Scholar
2	Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK, Weissenbach J, Marger D, Marger RS and Leigh IM: Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas. Arch Dermatol. 132:640–651. 1996. View Article : Google Scholar : PubMed/NCBI
3	Hennies HC, Hagedorn M and Reis A: Palmoplantar keratoderma in association with carcinoma of the esophagus maps to chromosome 17q distal to the keratin gene cluster. Genomics. 29:537–540. 1995. View Article : Google Scholar : PubMed/NCBI
4	Kelsell DP, Risk JM, Leigh IM, Stevens HP, Ellis A, Hennies HC, Reis A, Weissenbach J, Bishop DT, Spurr NK, et al: Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC). Hum Mol Genet. 5:857–860. 1996. View Article : Google Scholar : PubMed/NCBI
5	Risk JM, Field EA, Field JK, Whittaker J, Fryer A, Ellis A, Shaw JM, Friedmann PS, Bishop DT, Bodmer J, et al: Tylosis oesophageal cancer mapped. Nat Genet. 8:319–321. 1994. View Article : Google Scholar : PubMed/NCBI
6	Varela AB, Blanco Rodríguez MM, Boullosa PE and Silva JG: Tylosis A with squamous cell carcinoma of the oesophagus in a Spanish family. Eur J Gastroenterol Hepatol. 23:286–288. 2011. View Article : Google Scholar : PubMed/NCBI
7	Saarinen S, Vahteristo P, Lehtonen R, Aittomäki K, Launonen V, Kiviluoto T and Aaltonen LA: Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer. Fam Cancer. 11:525–528. 2012. View Article : Google Scholar : PubMed/NCBI
8	Risk JM, Evans KE, Jones J, Langan JE, Rowbottom L, McRonald FE, Mills HS, Ellis A, Shaw JM, Leigh IM, et al: Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial tylosis oesophageal cancer (TOC) locus. Oncogene. 21:6395–6402. 2002. View Article : Google Scholar : PubMed/NCBI
9	Langan JE, Cole CG, Huckle EJ, Byrne S, McRonald FE, Rowbottom L, Ellis A, Shaw JM, Leigh IM, Kelsell DP, et al: Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb: Sequencing does not identify the causative gene. Hum Genet. 114:534–540. 2004. View Article : Google Scholar : PubMed/NCBI
10	Iwaya T, Maesawa C, Ogasawara S and Tamura G: Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer. Gastroenterology. 114:1206–1210. 1998. View Article : Google Scholar : PubMed/NCBI
11	von Brevern M, Hollstein MC, Risk JM, Garde J, Bennett WP, Harris CC, Muehlbauer KR and Field JK: Loss of heterozygosity in sporadic oesophageal tumors in the tylosis oesophageal cancer (TOC) gene region of chromosome 17q. Oncogene. 17:2101–2105. 1998. View Article : Google Scholar : PubMed/NCBI
12	McRonald FE, Liloglou T, Xinarianos G, Hill L, Rowbottom L, Langan JE, Ellis A, Shaw JM, Field JK and Risk JM: Downregulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): Evidence for trans-allele repression. Hum Mol Genet. 15:1271–1277. 2006. View Article : Google Scholar : PubMed/NCBI
13	Blaydon DC, Etheridge SL, Risk JM, Hennies HC, Gay LJ, Carroll R, Plagnol V, McRonald FE, Stevens HP, Spurr NK, et al: RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet. 90:340–346. 2012. View Article : Google Scholar : PubMed/NCBI
14	Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, Suzuki Y, Shiraishi Y, Chiba K, Imoto S, Takahashi Y, et al: Genomic landscape of esophageal squamous cell carcinoma in a Japanese population. Gastroenterology. 150:1171–1182. 2016. View Article : Google Scholar : PubMed/NCBI
15	Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X, Sato Y, Okuno Y, Varela AM, Ding LW, et al: Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet. 46:467–473. 2014. View Article : Google Scholar : PubMed/NCBI
16	Song Y, Li L, Ou Y, Gao Z, Li E, Li X, Zhang W, Wang J, Xu L, Zhou Y, et al: Identification of genomic alterations in oesophageal squamous cell cancer. Nature. 509:91–95. 2014. View Article : Google Scholar : PubMed/NCBI
17	Gao YB, Chen ZL, Li JG, Hu XD, Shi XJ, Sun ZM, Zhang F, Zhao ZR, Li ZT, Liu ZY, et al: Genetic landscape of esophageal squamous cell carcinoma. Nat Genet. 46:1097–1102. 2014. View Article : Google Scholar : PubMed/NCBI
18	Iwaya T, Fukagawa T, Suzuki Y, Takahashi Y, Sawada G, Ishibashi M, Kurashige J, Sudo T, Tanaka F, Shibata K, et al: Contrasting expression patterns of histone mRNA and microRNA 760 in patients with gastric cancer. Clin Cancer Res. 19:6438–6449. 2013. View Article : Google Scholar : PubMed/NCBI
19	Yokobori T, Mimori K, Iwatsuki M, Ishii H, Onoyama I, Fukagawa T, Kuwano H, Nakayama KI and Mori M: p53-altered FBXW7 expression determines poor prognosis in gastric cancer cases. Cancer Res. 69:3788–3794. 2009. View Article : Google Scholar : PubMed/NCBI
20	Munkley J: The role of Sialyl-Tn in cancer. Int J Mol Sci. 17:2752016. View Article : Google Scholar : PubMed/NCBI
21	Li L, Lee KM, Han W, Choi JY, Lee JY, Kang GH, Park SK, Noh DY, Yoo KY and Kang D: Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer. Hum Mol Genet. 19:4273–4277. 2010. View Article : Google Scholar : PubMed/NCBI
22	Iwaya T, Maesawa C, Kimura T, Ogasawara S, Ikeda K, Kimura Y, Noda Y, Ishida K, Sato N, Saito K, et al: Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas. Oncol Rep. 13:703–707. 2005.PubMed/NCBI
23	Shivapurkar N, Stastny V, Okumura N, Girard L, Xie Y, Prinsen C, Thunnissen FB, Wistuba II, Czerniak B, Frenkel E, et al: Cytoglobin, the newest member of the globin family, functions as a tumor suppressor gene. Cancer Res. 68:7448–7456. 2008. View Article : Google Scholar : PubMed/NCBI