Expression and function of DEP domain-containing protein 1B in hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-3232.2024.02.015

Abstract

Abstract:

Objective

To investigate the expression and function of DEP domain-containing protein 1B (DEPDC1B) in hepatocellular carcinoma (HCC).

Methods

Public cancer databases (UALCAN, HPA) were searched to analyze the expression profile of DEPDC1B in HCC. RNAseq data (level 3) and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA) (https://portal.gdc.com). Kaplan-Meier survival analysis was performed using Log-rank test to compare the survival differences between two groups or among multiple groups. Prognostic value of DEPDC1B was assessed by using univariate and multivariate Cox analysis and the nomogram was established. The expression of DEPDC1B was inhibited by siRNA. The changes of cell invasion and migration were detected by Transwell chamber assay. Protein-protein interaction (PPI) of DEPDC1B was constructed by using STRING and the underlying mechanism in HCC was unraveled.

Results

The expression level of DEPDC1B gene in HCC tissues was significantly higher than that in normal tissues (P<0.05). The positive expression rate of DEPDC1B protein in HCC was 70%, ranking the first among 20 common cancers. TCGA data analysis showed that the overall survival and disease-free survival of HCC patients with high DEPDC1B expression were poor (HR=1.673, 1.434; P<0.05), which could be utilized as an independent prognostic factor of HCC and effectively predict the survival rate of HCC patients. Transwell chamber assay revealed that siRNA could significantly inhibit the expression levels of DEPDC1Bb in MHCC97-H and Hep3B cells. After down-regulating the expression of DEPDC1B, the invasion and migration capabilities of tumor cells were weakened. PPI network showed that DEPDC1B was intimately associated with tumor signaling pathways, such as TsC/mTOR, RTK, RAS/MAPK, PI3K/AKT, estrogen receptor, androgen receptor, epithelial-mesenchymal transition, DNA damage response, cell cycle and apoptosis, etc.

Conclusions

DEPDC1B is highly expressed in HCC. High expression of DEPDC1B is correlated with poor prognosis of HCC patients. Down-regulating the expression of DEPDC1B can weaken the invasion and migration capabilities of HCC cells.

Key words: Carcinoma, hepatocellular, DEP domain-containing 1B (DEPDC1B), Prognosis, Invasion, Migration

Hui Xia, Bin Dai, Jun Ran, Wei Wang, Zhao Gong, Cheng Zhou. Expression and function of DEP domain-containing protein 1B in hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(02): 205-213.

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References 21

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2]	Shi Y, Men X, Li X, et al. Research progress and clinical prospect of immunocytotherapy for the treatment of hepatocellular carcinoma[J]. Int Immunopharmacol, 2020(82):106351.
[3]	Chen X, Guo ZQ, Cao D, et al. Knockdown of DEPDC1B inhibits the development of glioblastoma[J]. Cancer Cell Int, 2020(20):310.
[4]	Zhang S, Shi W, Hu W, et al. DEP domain-containing protein 1B (DEPDC1B) promotes migration and invasion in pancreatic cancer through the Rac1/PAK1-LIMK1-Cofilin1 signaling pathway[J]. Onco Targets Ther, 2020(13):1481-1496.
[5]	Mosaddeghzadeh N, Ahmadian MR. The RHO family GTPases: mechanisms of regulation and signaling[J]. Cells, 2021, 10(7):1831.
[6]	Lawson CD, Ridley AJ. Rho GTPase signaling complexes in cell migration and invasion[J]. J Cell Biol, 2018, 217(2):447-457.
[7]	Bai S, Chen T, Du T, et al. High levels of DEPDC1B predict shorter biochemical recurrence-free survival of patients with prostate cancer[J]. Oncol Lett, 2017, 14(6):6801-6808.
[8]	Xu Y, Sun W, Zheng B, et al. DEPDC1B knockdown inhibits the development of malignant melanoma through suppressing cell proliferation and inducing cell apoptosis[J]. Exp Cell Res, 2019, 379(1):48-54.
[9]	Ganesan P, Kulik LM. Hepatocellular carcinoma: new developments[J]. Clin Liver Dis, 2023, 27(1):85-102.
[10]	Forner A, Reig M, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127):1301-1314.
[11]	Lai CH, Xu K, Zhou J, et al. DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1[J]. Cell Death Dis, 2020, 11(11):986.
[12]	Sun Y, Zhang Z. In silico identification of crucial genes and specific pathways in hepatocellular cancer[J]. Genet Test Mol Biomarkers, 2020, 24(5):296-308.
[13]	Wang L, Tang L, Xu R, et al. DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5[J]. Cell Death Dis, 2021, 12(8):753.
[14]	Su YF, Liang CY, Huang CY, et al. A putative novel protein, DEPDC1B, is overexpressed in oral cancer patients, and enhanced anchorage-independent growth in oral cancer cells that is mediated by Rac1 and ERK[J]. J Biomed Sci, 2014, 21(1):67.
[15]	Kikuchi R, Sampetrean O, Saya H, et al. Functional analysis of the DEPDC1 oncoantigen in malignant glioma and brain tumor initiating cells[J]. J Neurooncol, 2017, 133(2):297-307.
[16]	Dang XW, Pan Q, Lin ZH, et al. Overexpressed DEPDC1B contributes to the progression of hepatocellular carcinoma by CDK1[J]. Aging, 2021, 13(16):20094-20115.
[17]	Shen E, Zhang J, Lu Y. DEP domain containing 1B (DEPDC1B) exerts the tumor promoter in hepatocellular carcinoma through activating p53 signaling pathway via kinesin family member 23 (KIF23)[J]. Bioengineered, 2022, 13(1):1103-1114.
[18]	Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma[J]. Liver Transplant, 2005, 11(9):1086-1092.
[19]	Xu S, Zhan M, Wang J. Epithelial-to-mesenchymal transition in gallbladder cancer: from clinical evidence to cellular regulatory networks[J]. Cell Death Discov, 2017(3):17069.
[20]	Sengez B, Carr BI, Alotaibi H. EMT and inflammation: crossroads in HCC[J]. J Gastrointest Cancer, 2023, 54(1):204-212.
[21]	Liu X, Li T, Huang X, et al. DEPDC1B promotes migration and invasion in pancreatic ductal adenocarcinoma by activating the Akt/GSK3β/Snail pathway[J]. Oncol Lett, 2020, 20(5):146.

项目	OS			DFS
项目	例数	HR	P	例数	HR	P
性别
女性	118	1.96（1.11～3.46）	0.019	105	2.82（1.54～5.16）	<0.001
男性	246	2.20（1.40～3.44）	<0.001	208	1.69（1.08～2.65）	0.020
TNM分期
1	170	1.78（0.97～3.27）	0.060	153	1.63（0.94～2.81）	0.078
2	83	3.08（1.15～8.23）	0.018	74	1.90（0.79～4.58）	0.140
3	83	2.23（1.23～4.05）	0.001	68	2.69（1.23～5.87）	0.010
4	4			0
AJCC-T分期
1	181	1.78（1.00～3.17）	0.048	160	1.67（0.98～2.85）	0.056
2	90	3.15（1.20～8.28）	0.014	79	1.80（0.80～4.08）	0.150
3	78	2.18（1.19～4.01）	0.005	65	2.51（1.17～5.37）	0.015
4	13			6
组织学分级
1	55	5.02（1.66～15.13）	0.002	45	3.08（0.70～13.66）	0.120
2	174	2.53（1.31～4.88）	0.004	147	2.13（1.21～3.74）	0.008
3	118	1.98（1.09～3.61）	0.022	106	1.78（1.02～3.10）	0.040
4	12			11
血管侵犯
无	203	1.87（1.12～3.14）	0.016	175	1.44（0.88～2.36）	0.150
微血管	90	1.88（0.79～4.46）	0.150	81	2.63（1.16～5.97）	0.016
大血管	16			14
索拉非尼	29	6.21（0.77～49.84）	0.054	22	2.48（0.87～7.08）	0.082
饮酒
有	115	1.84（0.97～3.50）	0.059	98	2.60（1.41～4.79）	0.002
无	202	2.00（1.26～3.18）	0.003	182	1.63（1.05～2.55）	0.029
肝炎病毒
有	150	1.39（0.07～2.67）	0.310	138	1.27（0.74～2.15）	0.390
无	167	3.68（1.97～6.87）	<0.001	142	3.92（2.01～7.62）	<0.001

项目	OS			DFS
项目	例数	HR	P	例数	HR	P
性别
女性	118	1.96（1.11～3.46）	0.019	105	2.82（1.54～5.16）	<0.001
男性	246	2.20（1.40～3.44）	<0.001	208	1.69（1.08～2.65）	0.020
TNM分期
1	170	1.78（0.97～3.27）	0.060	153	1.63（0.94～2.81）	0.078
2	83	3.08（1.15～8.23）	0.018	74	1.90（0.79～4.58）	0.140
3	83	2.23（1.23～4.05）	0.001	68	2.69（1.23～5.87）	0.010
4	4			0
AJCC-T分期
1	181	1.78（1.00～3.17）	0.048	160	1.67（0.98～2.85）	0.056
2	90	3.15（1.20～8.28）	0.014	79	1.80（0.80～4.08）	0.150
3	78	2.18（1.19～4.01）	0.005	65	2.51（1.17～5.37）	0.015
4	13			6
组织学分级
1	55	5.02（1.66～15.13）	0.002	45	3.08（0.70～13.66）	0.120
2	174	2.53（1.31～4.88）	0.004	147	2.13（1.21～3.74）	0.008
3	118	1.98（1.09～3.61）	0.022	106	1.78（1.02～3.10）	0.040
4	12			11
血管侵犯
无	203	1.87（1.12～3.14）	0.016	175	1.44（0.88～2.36）	0.150
微血管	90	1.88（0.79～4.46）	0.150	81	2.63（1.16～5.97）	0.016
大血管	16			14
索拉非尼	29	6.21（0.77～49.84）	0.054	22	2.48（0.87～7.08）	0.082
饮酒
有	115	1.84（0.97～3.50）	0.059	98	2.60（1.41～4.79）	0.002
无	202	2.00（1.26～3.18）	0.003	182	1.63（1.05～2.55）	0.029
肝炎病毒
有	150	1.39（0.07～2.67）	0.310	138	1.27（0.74～2.15）	0.390
无	167	3.68（1.97～6.87）	<0.001	142	3.92（2.01～7.62）	<0.001

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