Prognostic value of ATAD3 gene cluster expression in hepatocellular carcinoma

Liu,Xiaoling; Li,Gang; Ai,Liang; Ye,Qiuwen; Yu,Tingdong; Yang,Burong

doi:10.3892/ol.2019.10454

Prognostic value of ATAD3 gene cluster expression in hepatocellular carcinoma

Authors:
- Xiaoling Liu
- Gang Li
- Liang Ai
- Qiuwen Ye
- Tingdong Yu
- Burong Yang
View Affiliations

Affiliations: Department of Geriatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Abdominal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: June 7, 2019 https://doi.org/10.3892/ol.2019.10454
Pages: 1304-1310
Copyright: © Liu 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

ATPase family AAA domain‑containing protein 3 (ATAD3) is a mitochondrial membrane‑bound ATPase that is involved in a number of cellular processes and is linked with the progression of various types of malignancies. In primates, the ATAD3 gene cluster contains ATAD3A, ATAD3B and ATAD3C. The association between ATAD3 gene cluster expression and hepatocellular carcinoma (HCC) remains unknown. Therefore, the present study examined the prognostic significance of ATAD3 gene cluster expression in patients with HCC. Box plots of expression differences between HCC and normal liver tissues for the ATAD3 family genes were obtained from the online tool Gene Expression Profiling Interactive Analysis. Data from 360 patients with HCC in The Cancer Genome Atlas database were analyzed. Kaplan‑Meier analysis and a Cox regression model were used to calculate median survival time (MST) and overall survival (OS). ATAD3A and ATAD3B expression levels were higher in HCC compared with normal liver tissues (P<0.05). However, ATAD3C expression was significantly decreased in HCC tissues compared with normal liver tissues (P<0.05). ATAD3A [P=0.017, hazard ratio (HR)=1.54, 95% confidence interval (CI)=1.08‑2.20; adjusted P=0.032; adjusted HR=1.52; 95% CI=1.04‑2.22] and ATAD3B (P=0.026, HR=1.49, 95% CI=1.05‑2.13; adjusted P=0.031, adjusted HR=1.52, 95% CI=1.04‑2.21) expression levels were significantly associated with OS. A joint‑effects analysis revealed that patients with high ATAD3A and ATAD3B expression had reduced OS rates compared with patients with low ATAD3A and ATAD3B expression (P=0.007, HR=1.77, 95% CI=1.16‑2.69; adjusted P=0.013, adjusted HR=1.76, 95% CI=1.13‑2.75). In conclusion, ATAD3A and ATAD3B may serve as potential prognostic biomarkers for patients with HCC.

View Figures

View References

1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Aravalli RN, Cressman EN and Steer CJ: Cellular and molecular mechanisms of hepatocellular carcinoma: An update. Arch Toxicol. 87:227–247. 2013. View Article : Google Scholar : PubMed/NCBI
3	Llovet JM, Schwartz M and Mazzaferro V: Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 25:181–200. 2005. View Article : Google Scholar : PubMed/NCBI
4	Xue C, Zhong Z, Ye S, Wang Y and Ye Q: Association between the overexpression of PBOV1 and the prognosis of patients with hepatocellular carcinoma. Oncol Lett. 16:3401–3407. 2018.PubMed/NCBI
5	Liu F, Pan Z, Zhang J, Ni J, Wang C, Wang Z, Gu F, Dong W, Zhou W and Liu H: Overexpression of RHEB is associated with metastasis and poor prognosis in hepatocellular carcinoma. Oncol Lett. 15:3838–3845. 2018.PubMed/NCBI
6	Yu T, Wang X, Zhu G, Han C, Su H, Liao X, Yang C, Qin W, Huang K and Peng T: The prognostic value of differentially expressed CYP3A subfamily members for hepatocellular carcinoma. Cancer Manag Res. 10:1713–1726. 2018. View Article : Google Scholar : PubMed/NCBI
7	Da Cruz S, Xenarios I, Langridge J, Vilbois F, Parone PA and Martinou JC: Proteomic analysis of the mouse liver mitochondrial inner membrane. J Biol Chem. 278:41566–41571. 2003. View Article : Google Scholar : PubMed/NCBI
8	Schaffrik M, Mack B, Matthias C, Rauch J and Gires O: Molecular characterization of the tumor-associated antigen AAA-TOB3. Cell Mol Life Sci. 63:2162–2174. 2006. View Article : Google Scholar : PubMed/NCBI
9	Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, et al: Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature. 421:231–237. 2003. View Article : Google Scholar : PubMed/NCBI
10	Hoffmann M, Bellance N, Rossignol R, Koopman WJ, Willems PH, Mayatepek E, Bossinger O and Distelmaier F: C. Elegans ATAD-3 is essential for mitochondrial activity and development. PLoS One. 4:e76442009. View Article : Google Scholar : PubMed/NCBI
11	Li S and Rousseau D: ATAD3, a vital membrane bound mitochondrial ATPase involved in tumor progression. J Bioenerg Biomembr. 44:189–197. 2012. View Article : Google Scholar : PubMed/NCBI
12	Frickey T and Lupas AN: Phylogenetic analysis of AAA proteins. J Struct Biol. 146:2–10. 2004. View Article : Google Scholar : PubMed/NCBI
13	Wang Y and Bogenhagen DF: Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane. J Biol Chem. 281:25791–25802. 2006. View Article : Google Scholar : PubMed/NCBI
14	He J, Mao CC, Reyes A, Sembongi H, Di Re M, Granycome C, Clippingdale AB, Fearnley IM, Harbour M, Robinson AJ, et al: The AAA+ protein ATAD3 has displacement loop binding properties and is involved in mitochondrial nucleoid organization. J Cell Biol. 176:141–146. 2007. View Article : Google Scholar : PubMed/NCBI
15	Bogenhagen DF, Rousseau D and Burke S: The layered structure of human mitochondrial DNA nucleoids. J Biol Chem. 283:3665–3675. 2008. View Article : Google Scholar : PubMed/NCBI
16	Gilquin B, Taillebourg E, Cherradi N, Hubstenberger A, Gay O, Merle N, Assard N, Fauvarque MO, Tomohiro S, Kuge O and Baudier J: The AAA+ ATPase ATAD3A controls mitochondrial dynamics at the interface of the inner and outer membranes. Mol Cell Biol. 30:1984–1996. 2010. View Article : Google Scholar : PubMed/NCBI
17	Hubstenberger A, Merle N, Charton R, Brandolin G and Rousseau D: Topological analysis of ATAD3A insertion in purified human mitochondria. J Bioenerg Biomembr. 42:143–150. 2010. View Article : Google Scholar : PubMed/NCBI
18	Desai R, Frazier AE, Durigon R, Patel H, Jones AW, Dalla Rosa I, Lake NJ, Compton AG, Mountford HS, Tucker EJ, et al: ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism. Brain. 140:1595–1610. 2017. View Article : Google Scholar : PubMed/NCBI
19	Gires O, Münz M, Schaffrik M, Kieu C, Rauch J, Ahlemann M, Eberle D, Mack B, Wollenberg B, Lang S, et al: Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology. Cell Mol Life Sci. 61:1198–1207. 2004. View Article : Google Scholar : PubMed/NCBI
20	Geuijen CA, Bijl N, Smit RC, Cox F, Throsby M, Visser TJ, Jongeneelen MA, Bakker AB, Kruisbeek AM, Goudsmit J and de Kruif J: A proteomic approach to tumour target identification using phage display, affinity purification and mass spectrometry. Eur J Cancer. 41:178–187. 2005. View Article : Google Scholar : PubMed/NCBI
21	Jiang Y, Liu X, Fang X and Wang X: Proteomic analysis of mitochondria in Raji cells following exposure to radiation: Implications for radiotherapy response. Protein Pept Lett. 16:1350–1359. 2009. View Article : Google Scholar : PubMed/NCBI
22	Fang HY, Chang CL, Hsu SH, Huang CY, Chiang SF, Chiou SH, Huang CH, Hsiao YT, Lin TY, Chiang IP, et al: ATPase family AAA domain-containing 3A is a novel anti-apoptotic factor in lung adenocarcinoma cells. J Cell Sci. 123:1171–1180. 2010. View Article : Google Scholar : PubMed/NCBI
23	Chen TC, Hung YC, Lin TY, Chang HW, Chiang IP, Chen YY and Chow KC: Human papillomavirus infection and expression of ATPase family AAA domain containing 3A, a novel anti-autophagy factor, in uterine cervical cancer. Int J Mol Med. 28:689–696. 2011.PubMed/NCBI
24	Huang KH, Chow KC, Chang HW, Lin TY and Lee MC: ATPase family AAA domain containing 3A is an anti-apoptotic factor and a secretion regulator of PSA in prostate cancer. Int J Mol Med. 28:9–15. 2011.PubMed/NCBI
25	Hubstenberger A, Labourdette G, Baudier J and Rousseau D: ATAD 3A and ATAD 3B are distal 1p-located genes differentially expressed in human glioma cell lines and present in vitro anti-oncogenic and chemoresistant properties. Exp Cell Res. 314:2870–2883. 2008. View Article : Google Scholar : PubMed/NCBI
26	Edge S: American joint committee on cancer; ACS. AJCC cancer staging manual. 7th edition. New York. Springer2009.
27	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
28	Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI
29	Rone MB, Midzak AS, Issop L, Rammouz G, Jagannathan S, Fan J, Ye X, Blonder J, Veenstra T and Papadopoulos V: Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocrinol. 26:1868–1882. 2012. View Article : Google Scholar : PubMed/NCBI
30	Li S, Lamarche F, Charton R, Delphin C, Gires O, Hubstenberger A, Schlattner U and Rousseau D: Expression analysis of ATAD3 isoforms in rodent and human cell lines and tissues. Gene. 535:60–69. 2014. View Article : Google Scholar : PubMed/NCBI
31	Ovaska K, Matarese F, Grote K, Charapitsa I, Cervera A, Liu C, Reid G, Seifert M, Stunnenberg HG and Hautaniemi S: Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer. PLoS Comput Biol. 9:e10031002013. View Article : Google Scholar : PubMed/NCBI
32	He J, Cooper HM, Reyes A, Di Re M, Sembongi H, Litwin TR, Gao J, Neuman KC, Fearnley IM, Spinazzola A, et al: Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis. Nucleic Acids Res. 40:6109–6121. 2012. View Article : Google Scholar : PubMed/NCBI
33	Merle N, Féraud O, Gilquin B, Hubstenberger A, Kieffer-Jacquinot S, Assard N, Bennaceur-Griscelli A, Honnorat J and Baudier J: ATAD3B is a human embryonic stem cell specific mitochondrial protein, re-expressed in cancer cells, that functions as dominant negative for the ubiquitous ATAD3A. Mitochondrion. 12:441–448. 2012. View Article : Google Scholar : PubMed/NCBI