Relationship between uc003yoa.3 and clinical prognosis of patients with hepatocellular carcinoma after hepatectomy

doi:10.3877/cma.j.issn.2095-3232.2020.01.019

Abstract

Abstract:

Objective

To investigate the effect of translation initiation factor uc003yoa.3 on the survival of patients with hepatocellular carcinoma (HCC) after hepatectomy and its role in the proliferation of HCC cells.

Methods

Clinical data of 215 patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from March to April 2010 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 182 patients were male and 33 female, aged 30-76 years with a median age of 49 years. The expression level of uc003yoa.3 mRNA of 5 patients' HCC and matched para-cancerous tissues was analyzed by gene chip. The expression of uc003yoa.3 mRNA in SMMC7721 cells after siRNA interference was measured by RT-PCR. Cell proliferation was detected by CCK-8. The uc003yoa.3 mRNA was statistically compared among different groups by univariate analysis and LSD-t test. The survival curve was delineated by Kaplan-Meier method. Survival analysis was performed by Log-rank test. The independent risk factors for the survival were identified by Cox's proportional hazards model.

Results

Gene chip analysis demonstrated that the expression of uc003yoa.3 mRNA in the HCC tissues was significantly higher than that in the matched para-cancerous tissues (Fold change=3.654, P<0.05). After SMMC7721 cells were treated with uc003yoa.3-siRNA for 4 d, the expression of uc003yoa.3 mRNA was 0.14±0.04, significantly lower than 0.22±0.06 in the control group (LSD-t=-1.119, P<0.05). The proliferation inhibition rate of SMMC7721 was 52%. Cox's multivariate analysis showed that high expression of uc003yoa.3, AFP>20μg/L, tumor diameter>5 cm and satellite lesion were the independent risk factors for tumor-free survival of HCC patients (HR=1.979, 1.841, 2.539, 2.358; P<0.05). High expression of uc003yoa.3 and tumor diameter>5 cm were the independent risk factors for the overall survival of HCC patients after hepatectomy (HR=1.927, 2.134; P<0.05).

Conclusions

High expression of uc003yoa.3 in HCC patients can promote the increase of malignant phenotype of HCC cells, which is an independent risk factor for the long-term survival of HCC patients after hepatectomy.

Key words: Carcinoma, hepatocellular, Hepatectomy, Initiation factors, uc003yoa, Prognosis

Qian Zhu, Chang Xu, Yun Li, Guoxiang Dai, Hong Cao, Deliang Guo, Jie Tang. Relationship between uc003yoa.3 and clinical prognosis of patients with hepatocellular carcinoma after hepatectomy[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2020, 09(01): 87-91.

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References 20

[1]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2]	Yuan SX, Wang J, Yang F, et al. Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma by derepression of CTNNB1[J]. Hepatology, 2016, 63(2):499-511.
[3]	Chen DL, Lu YX, Zhang JX, et al. Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression[J]. Theranostics, 2017, 7(19):4836-4849.
[4]	Yin Y, Long J, Sun Y, et al. The function and clinical significance of eIF3 in cancer[J]. Gene, 2018(673):130-133.
[5]	Gomes-Duarte A, Lacerda R, Menezes J, et al. eIF3: a factor for human health and disease[J]. RNA Biol, 2018, 15(1):26-34.
[6]	Mohammad MP, Munzarová Pondelícková V, Zeman J, et al. In vivo evidence that eIF3 stays bound to ribosomes elongating and terminating on short upstream ORFs to promote reinitiation[J]. Nucleic Acids Res, 2017, 45(5):2658-2674.
[7]	Schmidt C, Becker T, Heuer A, et al. Structure of the hypusinylated eukaryotic translation factor eIF-5A bound to the ribosome[J]. Nucleic Acids Res, 2016, 44(4):1944-1951.
[8]	Pisareva VP, Pisarev AV. DHX29 and eIF3 cooperate in ribosomal scanning on structured mRNAs during translation initiation[J]. RNA, 2016, 22(12):1859-1870.
[9]	Cappuzzo F, Varella-Garcia M, Rossi E, et al. MYC and EIF3H Coamplification significantly improve response and survival of non-small cell lung cancer patients (NSCLC) treated with gefitinib[J].J Thorac Oncol, 2009, 4(4):472-478.
[10]	Yin JY, Zhang JT, Zhang W, et al. eIF3a: a new anticancer drug target in the eIF family[J]. Cancer Lett, 2018(412):81-87.
[11]	Chen YT, Tsai HP, Wu CC, et al. Eukaryotic translation initiation factor 4E (eIF-4E) expressions are associated with poor prognosis in colorectal adenocarcinoma[J]. Pathol Res Pract, 2017, 213(5):490-495.
[12]	European Association for the Study of the Liver, Galle PR, Forner A, et al. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1):182-236.
[13]	Hasegawa K, Kokudo N, Makuuchi M, et al. Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based ona Japanese nationwide survey[J]. J Hepatol, 2013, 58(4): 724-729.
[14]	Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4):378-390.
[15]	Zhao W, Li X, Wang J, et al. Decreasing eukaryotic initiation factor 3C (EIF3C) suppresses proliferation and stimulates apoptosis in breast cancer cell lines through mammalian target of rapamycin (mTOR) pathway[J]. Med Sci Monit, 2017(23):4182-4191.
[16]	Liu GZ, Liu JZ, Li XQ, et al. Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells[J]. Mol Cell Biochem, 2018, 438(1/2):191-198.
[17]	Wang YW, Lin KT, Chen SC, et al. Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma[J]. Hepatology, 2013, 58(1):239-250.
[18]	Mahmood SF, Gruel N, Chapeaublanc E, et al. A siRNA screen identifies RAD21, uc003yoa.3, CHRAC1 and TANC2 as driver genes within the 8q23, 8q24.3 and 17q23 amplicons in breast cancer with effects on cell growth, survival and transformation[J]. Carcinogenesis, 2014, 35(3):670-682.
[19]	Graff JR, Zimmer SG. Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs[J]. Clin Exp Metastasis, 2003, 20(3):265-273.
[20]	Heo J, Reid T, Ruo L, et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer[J]. Nat Med, 2013, 19(3):329-336.

变量	无瘤生存			总体生存
变量	HR	95%CI	P值	HR	95%CI	P值
uc003yoa.3高表达	1.979	1.297～2.996	<0.001	1.927	1.775～2.582	0.002
AFP>20 μg/L	1.841	1.062～3.167	0.026	?	?	?
肿瘤直径>5 cm	2.539	1.520～4.256	<0.001	2.134	1.628～3.458	0.001
卫星灶	2.358	1.460～3.702	0.002	?	?	?

变量	无瘤生存			总体生存
变量	HR	95%CI	P值	HR	95%CI	P值
uc003yoa.3高表达	1.979	1.297～2.996	<0.001	1.927	1.775～2.582	0.002
AFP>20 μg/L	1.841	1.062～3.167	0.026	?	?	?
肿瘤直径>5 cm	2.539	1.520～4.256	<0.001	2.134	1.628～3.458	0.001
卫星灶	2.358	1.460～3.702	0.002	?	?	?

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