TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder

Liu,Ziru; Yang,Zhulin; Liu,Dongcai; Li,Daiqiang; Zou,Qiong; Yuan,Yuan; Li,Jinghe; Liang,Lufeng; Chen,Meigui; Chen,Senlin

doi:10.3892/ol.2014.1886

TSG101 and PEG10 are prognostic markers in squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder

Authors:
- Ziru Liu
- Zhulin Yang
- Dongcai Liu
- Daiqiang Li
- Qiong Zou
- Yuan Yuan
- Jinghe Li
- Lufeng Liang
- Meigui Chen
- Senlin Chen
View Affiliations

Affiliations: Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Pathology, Basic School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, Hunan Provincial People's Hospital, Changsha, Hunan 410007, P.R. China, Department of Pathology, Loudi Central Hospital, Loudi, Hunan 417011, P.R. China, Department of Pathology, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P.R. China
Published online on: February 14, 2014 https://doi.org/10.3892/ol.2014.1886
Pages: 1128-1138

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

The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) are currently not well documented, and as the prevalence of SC/ASC is uncommon in gallbladder cancers, a prognostic marker has not yet been found. In the present study, the expression of tumor susceptibility gene (TSG) 101 and paternally expressed gene (PEG) 10 was assessed in 46 SC/ASCs and 80 adenocarcinomas (ACs) using immunohistochemistry, and the samples were further analyzed to examine correlations with the clinicopathological characteristics. It was demonstrated that positive TSG101 and PEG10 expression were significantly associated with large tumor size, high tumor‑node‑metastasis (TNM) stage, lymph node metastasis, invasion and no resection (only biopsy) of SC/ASC and AC. The univariate Kaplan‑Meier analysis showed that positive TSG101 and PEG10 expression, and differentiation, tumor size, TNM stage, lymph node metastasis, invasion and surgical curability, is closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.001). The multivariate Cox regression analysis identified that positive TSG101 and PEG10 expression are independent factors for a poor‑prognosis in SC/ASC and AC patients. The present study indicates that positive TSG101 and PEG10 expression are closely associated with the clinical, pathological and biological behaviors, and a poor prognosis in gallbladder cancer.

View Figures

View References

1	Azad MB, Chen Y and Gibson SB: Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid Redox Signal. 11:777–790. 2009. View Article : Google Scholar : PubMed/NCBI
2	Pelicano H, Carney D and Huang P: ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 7:97–110. 2004. View Article : Google Scholar : PubMed/NCBI
3	Storz P: Reactive oxygen species in tumor progression. Front Biosci. 10:1881–1896. 2005. View Article : Google Scholar : PubMed/NCBI
4	Brigelius-Flohé R and Kipp A: Glutathione peroxidases in different stages of carcinogenesis. Biochim Biophys Acta. 1790:1555–1568. 2009.PubMed/NCBI
5	Wiseman H and Halliwell B: Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 313:17–29. 1996.PubMed/NCBI
6	Leto TL and Geiszt M: Role of Nox family NADPH oxidases in host defense. Antioxid Redox Signal. 8:1549–1561. 2006. View Article : Google Scholar : PubMed/NCBI
7	Cullen JJ, Mitros FA and Oberley LW: Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer. Pancreas. 26:23–27. 2003. View Article : Google Scholar
8	Ono R, Kobayashi S, Wagatsuma H, et al: A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics. 73:232–237. 2001. View Article : Google Scholar : PubMed/NCBI
9	Okabe H, Satoh S, Furukawa Y, et al: Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 63:3043–3048. 2003.PubMed/NCBI
10	Kainz B, Shehata M, Bilban M, et al: Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia. Int J Cancer. 121:1984–1993. 2007. View Article : Google Scholar : PubMed/NCBI
11	Tsuji K, Yasui K, Gen Y, et al: PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma. Cancer Genet Cytogenet. 198:118–125. 2010. View Article : Google Scholar : PubMed/NCBI
12	Chunsong H, Yuling H, Li W, et al: CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+CD5+ B cells. J Immunol. 177:6713–6722. 2006.PubMed/NCBI
13	Li CM, Margolin AA, Salas M, et al: PEG10 is a c-MYC target gene in cancer cells. Cancer Res. 66:665–672. 2006. View Article : Google Scholar : PubMed/NCBI
14	Ip WK, Lai PB, Wong NL, et al: Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma. Cancer Lett. 250:284–291. 2007. View Article : Google Scholar : PubMed/NCBI
15	Jie X, Lang C, Jian Q, et al: Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells. Oncogene. 26:5741–5751. 2007. View Article : Google Scholar : PubMed/NCBI
16	Lux A, Beil C, Majety M, et al: Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1. J Biol Chem. 280:8482–8493. 2005. View Article : Google Scholar : PubMed/NCBI
17	Ono R, Nakamura K, Inoue K, et al: Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality. Nat Genet. 38:101–106. 2006. View Article : Google Scholar : PubMed/NCBI
18	Li L and Cohen SN: Tsg101: a novel tumor susceptibility gene isolated by controlled homozygous functional knockout of allelic loci in mammalian cells. Cell. 85:319–329. 1996. View Article : Google Scholar
19	Young TW, Rosen DG, Mei FC, et al: Up-regulation of tumor susceptibility gene 101 conveys poor prognosis through suppression of p21 expression in ovarian cancer. Clin Cancer Res. 13:3848–3854. 2007. View Article : Google Scholar
20	Bashirova AA, Bleiber G, Qi Y, et al: Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1. J Virol. 80:6757–6763. 2006. View Article : Google Scholar
21	Liu RT, Huang CC, You HL, et al: Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas. Oncogene. 21:4830–4837. 2002. View Article : Google Scholar : PubMed/NCBI
22	Koon N, Schneider-Stock R, Sarlomo-Rikala M, et al: Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut. 53:235–240. 2004. View Article : Google Scholar : PubMed/NCBI
23	Ma XR, Edmund Sim UH, Pauline B, et al: Overexpression of WNT2 and TSG101 genes in colorectal carcinoma. Trop Biomed. 25:46–57. 2008.PubMed/NCBI
24	Zhu G, Gilchrist R, Borley N, et al: Reduction of TSG101 protein has a negative impact on tumor cell growth. Int J Cancer. 109:541–547. 2004. View Article : Google Scholar
25	Li L, Liao J, Ruland J, et al: A TSG101/MDM2 regulatory loop modulates MDM2 degradation and MDM2/p53 feedback control. Proc Natl Acad Sci USA. 98:1619–1624. 2001. View Article : Google Scholar : PubMed/NCBI
26	Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH and Fong Y: Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 11:310–315. 2004. View Article : Google Scholar : PubMed/NCBI
27	Roa JC, Tapia O, Cakir A, Basturk O, Dursun N, Akdemir D, Saka B, Losada H, Bagci P and Adsay NV: Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas. Mod Pathol. 24:1069–1078. 2011. View Article : Google Scholar : PubMed/NCBI
28	Kondo M, Dono K, Sakon M, et al: Adenosquamous carcinoma of the gallbladder. Hepatogastroenterology. 49:1230–1234. 2002.PubMed/NCBI
29	Muzio G, Maggiora M, Paiuzzi E, Oraldi M and Canuto RA: Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med. 52:735–746. 2012. View Article : Google Scholar : PubMed/NCBI
30	Zhao Y, You H, Liu F, et al: Differentially expressed gene profiles between multidrug resistant gastric adenocarcinoma cells and their parental cells. Cancer Lett. 185:211–218. 2002. View Article : Google Scholar
31	Shen H, Pan Y, Han Z, et al: Reversal of multidrug resistance of gastric cancer cells by downregulation of TSG101 with TSG101siRNA. Cancer Biol Ther. 3:561–565. 2004. View Article : Google Scholar