Year 2020 / Volume 112 / Number 1
Original
Elevated high mobility group A2 expression in liver cancer predicts poor patient survival

27-33

DOI: 10.17235/reed.2019.6365/2019

Yue-Chen Zhao, Yan Jiao, Yan-Qing Li, Zhuo Fu, Zhao-Ying Yang, Miao He,

Abstract
Background: liver cancer is a malignant tumor with a high morbidity and mortality that endangers human health. High mobility group A2 (HMGA2) is a chromosome associated protein that participates in embryogenesis, tissue development, tumorigenesis and development. Objective: to explore the relationship between HMGA2 expression and the clinicopathological parameters and survival of liver cancer patients using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (HCC) data. Methods: RNA-sequencing data and the corresponding clinical characteristics of the patients were downloaded from the Atlas database. The Chi-squared test was used to assess the relationship between HMGA2 expression and clinical variables. Cox regression analysis was used to compare survival rates between the high- and low-expressing groups; the p-values and Kaplan-Meier survival curves were compared using the log-rank test. Results: RNA-seq data from 373 cases of liver cancer cases were analyzed. HMGA2 was overexpressed in liver cancer and significantly associated with gender (p = 0.0357), T classification (p = 0.0063), clinical classification (p = 0.0026) and overall survival (p = 0.0386). According to the multivariate analysis, HMGA2 could independently predict overall survival in liver cancer. Conclusions: HMGA2 independently predicts poor prognosis in liver cancer and serves as a molecular marker to determine disease prognosis.
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References
1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
2. Wang HL, Mo DC, Zhong JH, et al. Systematic review of treatment strategy for recurrent hepatocellular carcinoma: Salvage liver transplantation or curative locoregional therapy. Medicine (Baltimore) 2019;98:e14498.
3. Diaz-Gonzalez A, Forner A, Rodriguez de Lope C, et al. New challenges in clinical research on hepatocellular carcinoma. Rev Esp Enferm Dig 2016;108:485-93.
4. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
5. Yang D, Tewary P, de la Rosa G, et al. The alarmin functions of high-mobility group proteins. Biochim Biophys Acta 2010;1799:157-63.
6. Zhang Q, Wang Y. High mobility group proteins and their post-translational modifications. Biochim Biophys Acta 2008;1784:1159-66.
7. Jakobiec FA, Stagner AM, Eagle RC, Jr., et al. Unusual pleomorphic adenoma of the lacrimal Gland: Immunohistochemical demonstration of PLAG1 and HMGA2 oncoproteins. Surv Ophthalmol 2017;62:219-226.
8. Qin Y, Niu Y, Liu F. Research progress of relationship between HMGA2 and tumors. Zhonghua Bing Li Xue Za Zhi 2014;43:65-7.
9. Chiappetta G, Avantaggiato V, Visconti R, et al. High level expression of the HMGI (Y) gene during embryonic development. Oncogene 1996;13:2439-46.
10. Rogalla P, Drechsler K, Frey G, et al. HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. Am J Pathol 1996;149:775-9.
11. Fedele M, Palmieri D, Fusco A. HMGA2: A pituitary tumour subtype-specific oncogene? Mol Cell Endocrinol 2010;326:19-24.
12. Xing F, Song Z, He Y. MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2. Biol Res 2018;51:50.
13. Ye ZH, Gui DW. miR539 suppresses proliferation and induces apoptosis in renal cell carcinoma by targeting high mobility group A2. Mol Med Rep 2018;17:5611-5618.
14. Chang HY, Ye SP, Pan SL, et al. Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer. Theranostics 2017;7:3889-3900.
15. Wang Y, Chen F, Zhao M, et al. The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186. J Biol Chem 2017;292:15395-15407.
16. Samur MK. RTCGAToolbox: a new tool for exporting TCGA Firehose data. PLoS One 2014;9:e106397.
17. Wu L, Wang Z, Lu R, et al. Expression of high mobility group A2 is associated with poor survival in hepatocellular carcinoma. Pathol Oncol Res 2012;18:983-7.
18. Sgarra R, Maurizio E, Zammitti S, et al. Macroscopic differences in HMGA oncoproteins post-translational modifications: C-terminal phosphorylation of HMGA2 affects its DNA binding properties. J Proteome Res 2009;8:2978-89.
19. Zhang N, Jiang W. Long noncoding RNA DANCR promotes HMGA2mediated invasion in lung adenocarcinoma cells. Oncol Rep 2019;41:1083-1090.
20. Tsubakihara Y, Moustakas A. Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor beta. Int J Mol Sci 2018;19.
21. Zha L, Zhang J, Tang W, et al. HMGA2 elicits EMT by activating the Wnt/beta-catenin pathway in gastric cancer. Dig Dis Sci 2013;58:724-33.
22. Watanabe S, Ueda Y, Akaboshi S, et al. HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. Am J Pathol 2009;174:854-68.
23. Kou B, Liu W, Tang X, et al. HMGA2 facilitates epithelial-mesenchymal transition in renal cell carcinoma by regulating the TGF-beta/Smad2 signaling pathway. Oncol Rep 2018;39:101-108.
24. Belge G, Radtke A, Meyer A, et al. Upregulation of the high mobility group AT-hook 2 gene in acute aortic dissection is potentially associated with endothelial-mesenchymal transition. Histol Histopathol 2011;26:1029-37.
25. Che N, Zhao XL, Sun T, et al. The role of Twist1 in hepatocellular carcinoma angiogenesis: a clinical study. Hum Pathol 2011;42:840-7.
26. Zhang H, Tang Z, Deng C, et al. HMGA2 is associated with the aggressiveness of tongue squamous cell carcinoma. Oral Dis 2017;23:255-264.
27. Esmailzadeh S, Mansoori B, Mohammadi A, et al. siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma. J Gastrointest Cancer 2017;48:156-163.
28. Natarajan S, Hombach-Klonisch S, Droge P, et al. HMGA2 inhibits apoptosis through interaction with ATR-CHK1 signaling complex in human cancer cells. Neoplasia 2013;15:263-80.
29. Liu Z, Wu K, Yang Z, et al. High-mobility group A2 overexpression is an unfavorable prognostic biomarker for nasopharyngeal carcinoma patients. Mol Cell Biochem 2015;409:155-62.
30. Strell C, Norberg KJ, Mezheyeuski A, et al. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC. Br J Cancer 2017;117:65-77.
31. Sun J, Sun B, Sun R, et al. HMGA2 promotes vasculogenic mimicry and tumor aggressiveness by upregulating Twist1 in gastric carcinoma. Sci Rep 2017;7:2229.
32. Sahengbieke S, Wang J, Li X, et al. Circulating cell-free high mobility group AT-hook 2 mRNA as a detection marker in the serum of colorectal cancer patients. J Clin Lab Anal 2018;32:e22332.
33. Mei LL, Wang WJ, Qiu YT, et al. miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma. PLoS One 2017;12:e0185636.
34. Li H, Zhao L, Zhang Z, et al. Roles of microRNA let-7b in papillary thyroid carcinoma by regulating HMGA2. Tumour Biol 2017;39:1010428317719274.
35. Li XX, Di X, Cong S, et al. The role of let-7 and HMGA2 in the occurrence and development of lung cancer: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2018;22:8353-8366.
1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300. DOI:10.3322/caac.20073
2. Wang HL, Mo DC, Zhong JH, et al. Systematic review of treatment strategy for recurrent hepatocellular carcinoma: Salvage liver transplantation or curative locoregional therapy. Medicine (Baltimore) 2019;98:e14498. DOI:10.1097/MD.0000000000014498
3. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. DOI:10.3322/caac.20107
4. Diaz-Gonzalez A, Forner A, Rodriguez de Lope C, et al. New challenges in clinical research on hepatocellular carcinoma. Rev Esp Enferm Dig 2016;108:485-93. DOI:10.17235/reed.2015.4012/2015
5. Yang D, Tewary P, de la Rosa G, et al. The alarmin functions of high-mobility group proteins. Biochim Biophys Acta 2010;1799:157-63. DOI:10.1016/j.bbagrm.2009.11.002
6. Zhang Q, Wang Y. High mobility group proteins and their post-translational modifications. Biochim Biophys Acta 2008;1784:1159-66. DOI:10.1016/j.bbapap.2008.04.028
7. Jakobiec FA, Stagner AM, Eagle RC, Jr., et al. Unusual pleomorphic adenoma of the lacrimal Gland: Immunohistochemical demonstration of PLAG1 and HMGA2 oncoproteins. Surv Ophthalmol 2017;62:219-226. DOI:10.1016/j.survophthal.2016.08.001
8. Chiappetta G, Avantaggiato V, Visconti R, et al. High level expression of the HMGI (Y) gene during embryonic development. Oncogene 1996;13:2439-46.
9. Rogalla P, Drechsler K, Frey G, et al. HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. Am J Pathol 1996;149:775-9.
10. Fedele M, Palmieri D, Fusco A. HMGA2: A pituitary tumour subtype-specific oncogene? Mol Cell Endocrinol 2010;326:19-24. DOI:10.1016/j.mce.2010.03.019
11. Liu Z, Wu K, Yang Z, et al. High-mobility group A2 overexpression is an unfavorable prognostic biomarker for nasopharyngeal carcinoma patients. Mol Cell Biochem 2015;409:155-62. DOI:10.1007/s11010-015-2521-0
12. Strell C, Norberg KJ, Mezheyeuski A, et al. Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC. Br J Cancer 2017;117:65-77. DOI:10.1038/bjc.2017.140
13. Sahengbieke S, Wang J, Li X, et al. Circulating cell-free high mobility group AT-hook 2 mRNA as a detection marker in the serum of colorectal cancer patients. J Clin Lab Anal 2018;32:e22332. DOI:10.1002/jcla.22332
14. Li XX, Di X, Cong S, et al. The role of let-7 and HMGA2 in the occurrence and development of lung cancer: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2018;22:8353-8366. DOI:10.26355/eurrev_201812_16533
15. Team RDCJC. R : A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2009;14:12-21.
16. Wickham H. Ggplot2 :elegant graphics for data analysis. Journal of the Royal Statistical Society 2011;174:245–246.
17. Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011;12:77. DOI:10.1186/1471-2105-12-77
18.Therneau TM, Grambsch PM, Modeling Survival Data: Extending the Cox Model, Springer, New York, 2000.
19. Jiao Y, Fu Z, Li Y, et al. High EIF2B5 mRNA expression and its prognostic significance in liver cancer: a study based on the TCGA and GEO database. Cancer Manag Res 2018;10:6003-6014. DOI:10.2147/cmar.S185459
20. Jiao Y, Fu Z, Li Y, et al. Aberrant FAM64A mRNA expression is an independent predictor of poor survival in pancreatic cancer. PLoS One 2019;14:e0211291. DOI:10.1371/journal.pone.0211291
21. Jiao Y, Li Y, Lu Z, et al. High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor Survival in Liver Cancer. Dig Dis Sci 2019;64:137-143. DOI:10.1007/s10620-018-5315-x
22. Jiao Y, Li Y, Jiang P, et al. PGM5: a novel diagnostic and prognostic biomarker for liver cancer. PeerJ 2019;7:e7070. DOI:10.7717/peerj.7070
23. Jiao Y, Li Y, Liu S, et al. ITGA3 serves as a diagnostic and prognostic biomarker for pancreatic cancer. Onco Targets Ther 2019;12:4141-4152. DOI:10.2147/ott.S201675
24. Wu L, Wang Z, Lu R, et al. Expression of high mobility group A2 is associated with poor survival in hepatocellular carcinoma. Pathol Oncol Res 2012;18:983-7. DOI:10.1007/s12253-012-9514-z
25. Sgarra R, Maurizio E, Zammitti S, et al. Macroscopic differences in HMGA oncoproteins post-translational modifications: C-terminal phosphorylation of HMGA2 affects its DNA binding properties. J Proteome Res 2009;8:2978-89. DOI:10.1021/pr900087r
26. Zhang N, Jiang W. Long noncoding RNA DANCR promotes HMGA2mediated invasion in lung adenocarcinoma cells. Oncol Rep 2019;41:1083-1090. DOI:10.3892/or.2018.6897
27. Xing F, Song Z, He Y. MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2. Biol Res 2018;51:50. DOI:10.1186/s40659-018-0199-y
28. Tsubakihara Y, Moustakas A. Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor beta. Int J Mol Sci 2018;19. DOI:10.3390/ijms19113672
29. Watanabe S, Ueda Y, Akaboshi S, et al. HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. Am J Pathol 2009;174:854-68. DOI:10.2353/ajpath.2009.080523
30. Belge G, Radtke A, Meyer A, et al. Upregulation of the high mobility group AT-hook 2 gene in acute aortic dissection is potentially associated with endothelial-mesenchymal transition. Histol Histopathol 2011;26:1029-37. DOI:10.14670/HH-26.1029
31. Esmailzadeh S, Mansoori B, Mohammadi A, et al. siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma. J Gastrointest Cancer 2017;48:156-163. DOI:10.1007/s12029-016-9871-z
32. Natarajan S, Hombach-Klonisch S, Droge P, et al. HMGA2 inhibits apoptosis through interaction with ATR-CHK1 signaling complex in human cancer cells. Neoplasia 2013;15:263-80. DOI:10.1593/neo.121988
33. Sun J, Sun B, Sun R, et al. HMGA2 promotes vasculogenic mimicry and tumor aggressiveness by upregulating Twist1 in gastric carcinoma. Sci Rep 2017;7:2229. DOI:10.1038/s41598-017-02494-6
34. Mei LL, Wang WJ, Qiu YT, et al. miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma. PLoS One 2017;12:e0185636. DOI:10.1371/journal.pone.0185636
35. Li H, Zhao L, Zhang Z, et al. Roles of microRNA let-7b in papillary thyroid carcinoma by regulating HMGA2. Tumour Biol 2017;39:1010428317719274. DOI:10.1177/1010428317719274
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Publication history

Received: 01/05/2019

Accepted: 25/07/2019

Online First: 11/12/2019

Published: 10/01/2020

Article revision time: 78 days

Article Online First time: 224 days

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