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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Hepatocellular Carcinoma | Primary research

Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma

Authors: Lei Lv, Yujia Zhao, Qinqin Wei, Ye Zhao, Qiyi Yi

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6), a key protein involved in synthetizing dihydrotestosterone, is abundant in the liver. Previous studies have suggested a role for dihydrotestosterone in modulating progress of various malignancies, and HSD17B6 dysfunction was associated with lung cancer and prostate cancer. However, little is known about the detailed role of HSD17B6 in hepatocellular carcinoma (HCC).

Methods

Clinical implication and survival data related to HSD17B6 expression in patients with HCC were obtained through TCGA, ICGC, ONCOMINE, GEO and HPA databases. Survival analysis plots were drawn with Kaplan–Meier Plotter. The ChIP-seq data were obtained from Cistrome DB. Protein–Protein Interaction and gene functional enrichment analyses were performed in STRING database. The correlations between HSD17B6 and tumor immune infiltrates was investigated via TIMER and xCell. The proliferation, migration and invasion of liver cancer cells transfected with HSD17B6 were evaluated by the CCK8 assay, wound healing test and transwell assay respectively. Expression of HSD17B6, TGFB1 and PD-L1 were assessed by quantitative RT-PCR.

Results

HSD17B6 expression was lower in HCC compared to normal liver and correlated with tumor stage and grade. Lower expression of HSD17B6 was associated with worse OS, PFS, RFS and DSS in HCC patients. HNF4A bound to enhancer and promoter regions of HSD17B6 gene, activating its transcription, and DNA methylation of HSD17B6 promoter negatively controlled the expression. HSD17B6 and its interaction partners were involved in androgen metabolism and biosynthesis in liver. HSD17B6 inhibited tumor cell proliferation, migration and invasion in liver cancer cells and low expression of HSD17B6 correlated with high immune cells infiltration, relative reduction of immune responses and multiple immune checkpoint genes expression in HCC, probably by regulating the expression of TGFB1.

Conclusions

This study indicate that HSD17B6 could be a new biomarker for the prognosis of HCC and an important negative regulator of immune responses in HCC.
Appendix
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Literature
1.
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018;68(6):394–424.CrossRef
3.
Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, Mariotto A, Lake AJ, Wilson R, Sherman RL, et al. Annual report to the nation on the status of cancer, 1975–2014, Featuring Survival. J Natl Cancer Inst. 2017;109:9.CrossRef
4.
Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, Gores G. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.PubMedCrossRef
5.
Huang XF, Luu-The V. Gene structure, chromosomal localization and analysis of 3-ketosteroid reductase activity of the human 3(alpha– > beta)-hydroxysteroid epimerase. Biochem Biophys Acta. 2001;1520(2):124–30.PubMed
6.
Huang XF, Luu-The V. Molecular characterization of a first human 3(alpha– > beta)-hydroxysteroid epimerase. J Biol Chem. 2000;275(38):29452–7.PubMedCrossRef
7.
Chan YX, Yeap BB. Dihydrotestosterone and cancer risk. Curr Opin Endocrinol Diabetes Obes. 2018;25(3):209–17.PubMedCrossRef
8.
Jones MR, Italiano L, Wilson SG, Mullin BH, Mead R, Dudbridge F, Watts GF, Stuckey BG. Polymorphism in HSD17B6 is associated with key features of polycystic ovary syndrome. Fertil Steril. 2006;86(5):1438–46.PubMedCrossRef
9.
Jones MR, Mathur R, Cui J, Guo X, Azziz R, Goodarzi MO. Independent confirmation of association between metabolic phenotypes of polycystic ovary syndrome and variation in the type 6 17beta-hydroxysteroid dehydrogenase gene. J Clin Endocrinol Metabol. 2009;94(12):5034–8.CrossRef
10.
Jernberg E, Thysell E, Bovinder Ylitalo E, Rudolfsson S, Crnalic S, Widmark A, Bergh A, Wikstrom P. Characterization of prostate cancer bone metastases according to expression levels of steroidogenic enzymes and androgen receptor splice variants. PLoS ONE. 2013;8(11):e77407.PubMedPubMedCentralCrossRef
11.
Ma Q, Xu Y, Liao H, Cai Y, Xu L, Xiao D, Liu C, Pu W, Zhong X, Guo X. Identification and validation of key genes associated with non-small-cell lung cancer. J Cell Physiol. 2019;234(12):22742–52.PubMedCrossRef
12.
White DL, Liu Y, Garcia J, El-Serag HB, Jiao L, Tsavachidis S, Franco LM, Lee JS, Tavakoli-Tabasi S, Moore D, et al. Sex hormone pathway gene polymorphisms are associated with risk of advanced hepatitis C-related liver disease in males. Int J Mol Epidemiol Genet. 2014;5(3):164–76.PubMedPubMedCentral
13.
Nagy A, Lanczky A, Menyhart O, Gyorffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227.PubMedPubMedCentralCrossRef
14.
Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.CrossRef
15.
Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.PubMedCrossRef
16.
Thul PJ, Akesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, Alm T, Asplund A, Bjork L, Breckels LM, et al. A subcellular map of the human proteome. Science. 2017;356:6340.CrossRef
17.
Uhlen M, Zhang C, Lee S, Sjostedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, et al. A pathology atlas of the human cancer transcriptome. Science. 2017;357:6352.CrossRef
18.
Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef
19.
Lian Q, Wang S, Zhang G, Wang D, Luo G, Tang J, Chen L, Gu J. HCCDB: a database of hepatocellular carcinoma expression atlas. Genomics Proteomics Bioinf. 2018;16(4):269–75.CrossRef
20.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545–50.PubMedCrossRefPubMedCentral
21.
Zhang JX, Chen ZH, Xu Y, Chen JW, Weng HW, Yun M, Zheng ZS, Chen C, Wu BL, Li EM, et al. Downregulation of MicroRNA-644a promotes esophageal squamous cell carcinoma aggressiveness and stem cell-like phenotype via dysregulation of PITX2. Clin Cancer Res. 2017;23(1):298–310.PubMedCrossRef
22.
23.
Ma WL, Hsu CL, Yeh CC, Wu MH, Huang CK, Jeng LB, Hung YC, Lin TY, Yeh S, Chang C. Hepatic androgen receptor suppresses hepatocellular carcinoma metastasis through modulation of cell migration and anoikis. Hepatology. 2012;56(1):176–85.PubMedCrossRef
24.
Thakur A, Wong JCH, Wang EY, Lotto J, Kim D, Cheng JC, Mingay M, Cullum R, Moudgil V, Ahmed N, et al. Hepatocyte nuclear factor 4-alpha is essential for the active epigenetic state at enhancers in mouse liver. Hepatology. 2019;70(4):1360–76.PubMedCrossRef
25.
Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473(7345):43–9.PubMedPubMedCentralCrossRef
26.
Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E, Sheffield NC, Stergachis AB, Wang H, Vernot B, et al. The accessible chromatin landscape of the human genome. Nature. 2012;489(7414):75–82.PubMedPubMedCentralCrossRef
27.
Gertz J, Savic D, Varley KE, Partridge EC, Safi A, Jain P, Cooper GM, Reddy TE, Crawford GE, Myers RM. Distinct properties of cell-type-specific and shared transcription factor binding sites. Mol Cell. 2013;52(1):25–36.PubMedCrossRef
28.
Schmidt D, Schwalie PC, Ross-Innes CS, Hurtado A, Brown GD, Carroll JS, Flicek P, Odom DT. A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res. 2010;20(5):578–88.PubMedPubMedCentralCrossRef
29.
Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C, Zhu M, Wu J, Shi X, Taing L, et al. Cistrome data browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res. 2017;45(D1):D658–62.PubMedCrossRef
30.
Zheng R, Wan C, Mei S, Qin Q, Wu Q, Sun H, Chen CH, Brown M, Zhang X, Meyer CA, et al. Cistrome data browser: expanded datasets and new tools for gene regulatory analysis. Nucleic Acids Res. 2019;47(D1):D729–35.PubMedCrossRef
31.
Robertson AG, Bilenky M, Tam A, Zhao Y, Zeng T, Thiessen N, Cezard T, Fejes AP, Wederell ED, Cullum R, et al. Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome Res. 2008;18(12):1906–17.PubMedPubMedCentralCrossRef
32.
Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, et al. The human mitochondrial transcriptome. Cell. 2011;146(4):645–58.PubMedPubMedCentralCrossRef
33.
Velasco G, Hube F, Rollin J, Neuillet D, Philippe C, Bouzinba-Segard H, Galvani A, Viegas-Pequignot E, Francastel C. Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues. Proc Natl Acad Sci USA. 2010;107(20):9281–6.PubMedCrossRefPubMedCentral
34.
Maurel M, Samali A, Chevet E. Endoplasmic reticulum stress: at the crossroads of inflammation and metabolism in hepatocellular carcinoma development. Cancer Cell. 2014;26(3):301–3.PubMedCrossRef
35.
Domingues P, Gonzalez-Tablas M, Otero A, Pascual D, Miranda D, Ruiz L, Sousa P, Ciudad J, Goncalves JM, Lopes MC, et al. Tumor infiltrating immune cells in gliomas and meningiomas. Brain Behav Immun. 2016;53:1–15.PubMedCrossRef
36.
Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell. 2017;169(7):1342–56.PubMedCrossRef
37.
Sun H, Liu L, Huang Q, Liu H, Huang M, Wang J, Wen H, Lin R, Qu K, Li K, et al. Accumulation of tumor-infiltrating CD49a(+) NK cells correlates with poor prognosis for human hepatocellular carcinoma. Cancer Immunol Res. 2019;7(9):1535–46.PubMedCrossRef
38.
Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, Liu XS. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77(21):e108–10.PubMedPubMedCentralCrossRef
39.
40.
Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, Castro de Moura M, Putra J, Camprecios G, Bassaganyas L, Akers N, et al. Identification of an immune-specific class of hepatocellular carcinoma. Based on molecular features. Gastroenterology. 2017;153(3):812–26.PubMedCrossRef
41.
42.
Chen WY, Tsai YC, Yeh HL, Suau F, Jiang KC, Shao AN, Huang J, Liu YN. Loss of SPDEF and gain of TGFBI activity after androgen deprivation therapy promote EMT and bone metastasis of prostate cancer. Sci Signal. 2017;10:492.
43.
Muthusamy S, Andersson S, Kim HJ, Butler R, Waage L, Bergerheim U, Gustafsson JA. Estrogen receptor beta and 17beta-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer. Proc Natl Acad Sci USA. 2011;108(50):20090–4.PubMedCrossRefPubMedCentral
44.
Ishizaki F, Nishiyama T, Kawasaki T, Miyashiro Y, Hara N, Takizawa I, Naito M, Takahashi K. Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer. Sci Rep. 2013;3:1528.PubMedPubMedCentralCrossRef
45.
Hlady RA, Tiedemann RL, Puszyk W, Zendejas I, Roberts LR, Choi JH, Liu C, Robertson KD. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis. Oncotarget. 2014;5(19):9425–43.PubMedPubMedCentralCrossRef
46.
Guechot J, Peigney N, Ballet F, Vaubourdolle M, Giboudeau J, Poupon R. Sex hormone imbalance in male alcoholic cirrhotic patients with and without hepatocellular carcinoma. Cancer. 1988;62(4):760–2.PubMedCrossRef
47.
Dai R, Yan D, Li J, Chen S, Liu Y, Chen R, Duan C, Wei M, Li H, He T. Activation of PKR/eIF2alpha signaling cascade is associated with dihydrotestosterone-induced cell cycle arrest and apoptosis in human liver cells. J Cell Biochem. 2012;113(5):1800–8.PubMed
48.
Lim IK, Joo HJ, Choi KS, Sueoka E, Lee MS, Ryu MS, Fujiki H. Protection of 5alpha-dihydrotestosterone against TGF-beta-induced apoptosis in FaO cells and induction of mitosis in HepG2 cells. Int J Cancer. 1997;72(2):351–5.PubMedCrossRef
49.
Jie X, Lang C, Jian Q, Chaoqun L, Dehua Y, Yi S, Yanping J, Luokun X, Qiuping Z, Hui W, et al. Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells. Oncogene. 2007;26(39):5741–51.PubMedCrossRef
50.
Ma WL, Lai HC, Yeh S, Cai X, Chang C. Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis. Endocr Relat Cancer. 2014;21(3):R165–82.PubMedPubMedCentralCrossRef
51.
Ma WL, Hsu CL, Wu MH, Wu CT, Wu CC, Lai JJ, Jou YS, Chen CW, Yeh S, Chang C. Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. Gastroenterology. 2008;135(3):947–55.PubMedCrossRef
52.
van Rooijen JM, Qiu SQ, Timmer-Bosscha H, van der Vegt B, Boers JE, Schroder CP, de Vries EGE. Androgen receptor expression inversely correlates with immune cell infiltration in human epidermal growth factor receptor 2-positive breast cancer. Eur J Cancer. 2018;103:52–60.PubMedCrossRef
53.
Fan Y, Hu S, Liu J, Xiao F, Li X, Yu W, Cui Y, Sun M, Lv T, He Q, et al. Low intraprostatic DHT promotes the infiltration of CD8+ T cells in BPH tissues via modulation of CCL5 secretion. Mediat Inflamm. 2014;2014:397815.CrossRef
54.
Yang L, Pang Y, Moses HL. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol. 2010;31(6):220–7.PubMedPubMedCentralCrossRef
55.
56.
57.
Ihling C, Naughton B, Zhang Y, Rolfe PA, Frick-Krieger E, Terracciano LM, Dussault I. Observational study of PD-L1, TGF-beta, and immune cell infiltrates in hepatocellular carcinoma. Front Med (Lausanne). 2019;6:15.CrossRef
58.
Jung HI, Jeong D, Ji S, Ahn TS, Bae SH, Chin S, Chung JC, Kim HC, Lee MS, Baek MJ. Overexpression of PD-L1 and PD-L2 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res Treat. 2017;49(1):246–54.PubMedCrossRef
59.
Katz LH, Likhter M, Jogunoori W, Belkin M, Ohshiro K, Mishra L. TGF-beta signaling in liver and gastrointestinal cancers. Cancer Lett. 2016;379(2):166–72.PubMedPubMedCentralCrossRef
60.
Wang J, Li M, Wang Y, Liu X. Integrating subpathway analysis to identify candidate agents for hepatocellular carcinoma. Onco Targets Ther. 2016;9:1221–30.PubMedPubMedCentralCrossRef
61.
Agdashian D, ElGindi M, Xie C, Sandhu M, Pratt D, Kleiner DE, Figg WD, Rytlewski JA, Sanders C, Yusko EC, et al. The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma. Cancer Immunol Immunother. 2019;68(4):599–608.PubMedPubMedCentralCrossRef
62.
Chen J, Gingold JA, Su X. Immunomodulatory TGF-beta signaling in hepatocellular carcinoma. Trends Mol Med. 2019;25(11):1010–23.PubMedCrossRef
63.
Tiegs G, Lohse AW. Immune tolerance: what is unique about the liver. J Autoimmun. 2010;34(1):1–6.PubMedCrossRef
64.
Lugade AA, Kalathil S, Miller A, Iyer R, Thanavala Y. High immunosuppressive burden in advanced hepatocellular carcinoma patients: can effector functions be restored? Oncoimmunology. 2013;2(7):e24679.PubMedPubMedCentralCrossRef
65.
Chen CH, Seguin-Devaux C, Burke NA, Oriss TB, Watkins SC, Clipstone N, Ray A. Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation. J Exp Med. 2003;197(12):1689–99.PubMedPubMedCentralCrossRef
66.
Gorelik L, Constant S, Flavell RA. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med. 2002;195(11):1499–505.PubMedPubMedCentralCrossRef
67.
Wiener Z, Kohalmi B, Pocza P, Jeager J, Tolgyesi G, Toth S, Gorbe E, Papp Z, Falus A. TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol. 2007;127(4):906–14.PubMedCrossRef
68.
Zhou X, Mao Y, Zhu J, Meng F, Chen Q, Tao L, Li R, Fu F, Liu C, Hu Y, et al. TGF-beta1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis. Oncotarget. 2016;7(41):67196–211.PubMedPubMedCentralCrossRef
69.
Peres RS, Donate PB, Talbot J, Cecilio NT, Lobo PR, Machado CC, Lima KWA, Oliveira RD, Carregaro V, Nakaya HI, et al. TGF-beta signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis. J Autoimmun. 2018;90:49–58.PubMedCrossRef
70.
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+ CD25− naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198(12):1875–86.PubMedPubMedCentralCrossRef
71.
Park HB, Paik DJ, Jang E, Hong S, Youn J. Acquisition of anergic and suppressive activities in transforming growth factor-beta-costimulated CD4+ CD25− T cells. Int Immunol. 2004;16(8):1203–13.PubMedCrossRef
72.
Zheng SG, Gray JD, Ohtsuka K, Yamagiwa S, Horwitz DA. Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+ CD25− precursors. J Immunol. 2002;169(8):4183–9.PubMedCrossRef
73.
Song S, Yuan P, Wu H, Chen J, Fu J, Li P, Lu J, Wei W. Dendritic cells with an increased PD-L1 by TGF-beta induce T cell anergy for the cytotoxicity of hepatocellular carcinoma cells. Int Immunopharmacol. 2014;20(1):117–23.PubMedCrossRef
74.
Donkor MK, Sarkar A, Savage PA, Franklin RA, Johnson LK, Jungbluth AA, Allison JP, Li MO. T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-beta1 cytokine. Immunity. 2011;35(1):123–34.PubMedPubMedCentralCrossRef
Metadata
Title
Downexpression of HSD17B6 correlates with clinical prognosis and tumor immune infiltrates in hepatocellular carcinoma
Authors
Lei Lv
Yujia Zhao
Qinqin Wei
Ye Zhao
Qiyi Yi
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01298-5

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