Relationship of the expression levels of XIAP and p53 genes in hepatocellular carcinoma and the prognosis of patients

Li,Zhiqin; Han,Chunfang; Feng,Jing

doi:10.3892/ol.2017.6681

Relationship of the expression levels of XIAP and p53 genes in hepatocellular carcinoma and the prognosis of patients

Authors:
- Zhiqin Li
- Chunfang Han
- Jing Feng
View Affiliations

Affiliations: Department of Infectious Diseases, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: July 27, 2017 https://doi.org/10.3892/ol.2017.6681
Pages: 4037-4042
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

In this study, we measured mRNA and protein expression levels of X‑linked inhibitor of apoptosis protein (XIAP) and p53 in hepatocellular carcinoma (HCC) and analyzed their relationships to clinicopathological parameters and the prognosis of the patients. Samples were obtained from tumors and tumor-adjacent normal tissues from 70 patients with HCC who were hospitalized in Weifang People's Hospital from January 2009 to December 2011. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to detect the mRNA and protein expression levels, respectively. The clinical data of patients who were followed for 5 years from the day of the tumor-resection surgery were collected in detailed clinical histories. Statistical analyses were used to find relationships between the XIAP and p53 levels and the clinical variables and 5-year survival of patients. Our qPCR results showed that the mRNA expression levels of XIAP and p53 in HCC tumors were significantly higher than those in tumor-adjacent normal tissues. At the same time, IHC results showed that the positive expression rates of XIAP and p53 in HCC in tumors were 81.4% (57/70) and 72.9% (51/70), respectively and their high expression was related to invasion, metastasis and tumor staging. The overall 5-year survival rate of the patients was 15.7% (11/70). Single factor survival analysis showed that both XIAP and p53 were influencing factors of the overall survival rate of patients with HCC (P<0.01). In conclusion, high expression levels of XIAP and p53 are closely related to clinicopathological parameters of patients with HCC, especially related to invasion, metastasis and tumor staging. XIAP and p53 levels can be used as reference values to guide the treatment of HCC and estimate the prognosis.

View Figures

View References

1	Yang JD and Roberts LR: Epidemiology and management of hepatocellular carcinoma. Infect Dis Clin North Am. 24:899–919. 2010. View Article : Google Scholar : PubMed/NCBI
2	Duan XY, Zhang L, Fan JG and Qiao L: NAFLD leads to liver cancer: Do we have sufficient evidence? Cancer Lett. 345:230–234. 2014. View Article : Google Scholar : PubMed/NCBI
3	Karagozian R, Derdák Z and Baffy G: Obesity-associated mechanisms of hepatocarcinogenesis. Metabolism. 63:607–617. 2014. View Article : Google Scholar : PubMed/NCBI
4	Nakagawa H, Umemura A, Taniguchi K, Font-Burgada J, Dhar D, Ogata H, Zhong Z, Valasek MA, Seki E, Hidalgo J, et al: ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 26:331–343. 2014. View Article : Google Scholar : PubMed/NCBI
5	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
6	Han XJ, Dong BW, Liang P, Yu XL and Yu DJ: Local cellular immune response induced by ultrasound-guided tumor bed superantigen injection after percutaneous microwave coagulation therapy for liver cancer. Zhonghua Zhong Liu Za Zhi. 31:602–606. 2009.(In Chinese). PubMed/NCBI
7	Deveraux QL and Reed JC: IAP family proteins - suppressors of apoptosis. Genes Dev. 13:239–252. 1999. View Article : Google Scholar : PubMed/NCBI
8	Holcik M, Gibson H and Korneluk RG: XIAP: Apoptotic brake and promising therapeutic target. Apoptosis. 6:253–261. 2001. View Article : Google Scholar : PubMed/NCBI
9	Liston P, Fong WG and Korneluk RG: The inhibitors of apoptosis: There is more to life than Bcl2. Oncogene. 22:8568–8580. 2003. View Article : Google Scholar : PubMed/NCBI
10	Maniwa Y, Yoshimura M, Obayashi C, Inaba M, Kiyooka K, Kanki M and Okita Y: Association of p53 gene mutation and telomerase activity in resectable non-small cell lung cancer. Chest. 120:589–594. 2001. View Article : Google Scholar : PubMed/NCBI
11	Graziano SL, Tatum A, Herndon JE II, Box J, Memoli V, Green MR and Kern JA: Use of neuroendocrine markers, p53 and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: A cancer and leukemia group B study. Lung Cancer. 33:115–123. 2001. View Article : Google Scholar : PubMed/NCBI
12	Green DR and Kroemer G: Cytoplasmic functions of the tumour suppressor p53. Nature. 458:1127–1130. 2009. View Article : Google Scholar : PubMed/NCBI
13	Song LP, Li YP, Wang N, Li WW, Ren J, Qiu SD, Wang QY and Yang GX: NT4(Si)-p53(N15)-antennapedia induces cell death in a human hepatocellular carcinoma cell line. World J Gastroenterol. 15:5813–5820. 2009. View Article : Google Scholar : PubMed/NCBI
14	Hu W, Wang F, Tang J, Liu X, Yuan Z, Nie C and Wei Y: Proapoptotic protein Smac mediates apoptosis in cisplatin-resistant ovarian cancer cells when treated with the antitumor agent AT101. J Biol Chem. 287:68–80. 2012. View Article : Google Scholar : PubMed/NCBI
15	Hussain AR, Uddin S, Ahmed M, Bu R, Ahmed SO, Abubaker J, Sultana M, Ajarim D, Al-Dayel F, Bavi PP, et al: Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling. J Pathol. 222:180–190. 2010. View Article : Google Scholar : PubMed/NCBI
16	Shangary S and Wang S: Targeting the MDM2-p53 interaction for cancer therapy. Clin Cancer Res. 14:5318–5324. 2008. View Article : Google Scholar : PubMed/NCBI
17	Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, et al: Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA. 105:3933–3938. 2008. View Article : Google Scholar : PubMed/NCBI
18	Scoumanne A and Chen X: Protein methylation: A new mechanism of p53 tumor suppressor regulation. Histol Histopathol. 23:1143–1149. 2008.PubMed/NCBI
19	Lu C and El-Deiry WS: Targeting p53 for enhanced radio- and chemo-sensitivity. Apoptosis. 14:597–606. 2009. View Article : Google Scholar : PubMed/NCBI
20	Hall PA, Ray A, Lemoine NR, Midgley CA, Krausz T and Lane DP: p53 immunostaining as a marker of malignant disease in diagnostic cytopathology. Lancet. 338:5131991. View Article : Google Scholar : PubMed/NCBI
21	Martinazzi M, Crivelli F, Zampatti C and Martinazzi S: Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study. Am J Clin Pathol. 100:213–217. 1993. View Article : Google Scholar : PubMed/NCBI
22	Chen W, Li J, Liu C, Chen X, Zhu Y, Yang Y, Gong Y, Wang T, Miao X and Nie X: A functional p53 responsive polymorphism in KITLG, rs4590952, does not affect the risk of breast cancer. Sci Rep. 4:63712014. View Article : Google Scholar : PubMed/NCBI
23	Ramp U, Krieg T, Caliskan E, Mahotka C, Ebert T, Willers R, Gabbert HE and Gerharz CD: XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. Hum Pathol. 35:1022–1028. 2004. View Article : Google Scholar : PubMed/NCBI
24	Hong Y, Zhong R and Hang Z: The association study and its clinical significance of the expression of P53, AR and ER in the primary hepatocelluar carcinoma (liver cancer) and surrounding tissue. Int Med Health Guid News. 12:12–14. 2006.