Expression level and clinical significance of INHBA in hepatocellular carcinoma

doi:10.3877/cma.j.issn.2095-3232.2022.05.018

Abstract

Abstract:

Objective

To investigate the expression level of inhibin β-A (INHBA) in hepatocellular carcinoma (HCC) and its relationship with clinical prognosis.

Methods

HCC tissue samples were collected from 81 patients with HCC undergoing surgical resection in the First Affiliated Hospital of Guangzhou Medical University from February 2009 to November 2013, and 30 adjacent tissues were obtained as the controls. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 74 patients were male and 7 female, aged from 32 to 81 years, with a median age of 53 years. The expression level of INHBA was detected by immunohistochemistry. The expression rate of INHBA was compared between the HCC and adjacent tissues, and the relationship between INHBA expression and clinicopathological parameters of HCC patients was analyzed by Chi-square test. Survival analysis was conducted by Kaplan-Meier method and Log-rank test. The risk factors of clinical prognosis of HCC patients were identified by Cox's proportional hazards regression model.

Results

The expression rate of INHBA in the HCC tissues was 42%(34/81), significantly higher than 13%(4/30) in the adjacent tissues (χ²=9.276, P<0.05). The expression of INHBA was correlated with the degree of tumor differentiation and AJCC staging (χ²=15.499, 9.100; P<0.05). Survival analysis showed that clinical prognosis of patients with high expression of INHBA was significantly worse than that of patients with low expression (χ²=11.721, P<0.05). Cox's regression analysis indicated that AJCC stage Ⅲ and high expression of INHBA were the independent risk factors for the clinical prognosis of HCC patients (HR=4.316, 2.612; P<0.05).

Conclusions

INHBA is highly expressed in HCC tissues, which is associated with the tumor differentiation and AJCC staging. HCC patients with high expression of INHBA have poorer clinical prognosis.

Key words: Carcinoma, hepatocellular, Inhibin β-A, Prognosis, Immunohistochemistry

Baorong Chen, Xi Li, Jiani Wang, Yuhang Pan. Expression level and clinical significance of INHBA in hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2022, 11(05): 519-523.

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References 24

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[2]	杨继春, 于树青, 高乐, 等. 全球肝癌筛查指南制订现状的系统综述[J]. 中华流行病学杂志, 2020, 41(7):4007-4013.
[3]	Yin JM, Sun LB，Zheng JS, et al. Copper chelation by trientine dihydrochloride inhibits liver RFA-induced inflammatory responses in vivo[J]. Inflamm Res, 2016, 65(12):1009-1020.
[4]	Brown CW, Houston-Hawkins DE, Woodruff TK, et al. Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions[J]. Nat Genet, 2000, 25(4):453-457.
[5]	Namwanje M，Brown CW. Activins and inhibins: roles in development, physiology, and disease[J]. Cold Spring Harb Perspect Biol, 2016, 8(7):a021881.
[6]	Lyu S, Jiang C, Xu R, et al. INHBA upregulation correlates with poorer prognosis in patients with esophageal squamous cell carcinoma[J]. Cancer Manag Res, 2018(10):1585-1596.
[7]	Okano M, Yamamoto H, Ohkuma H, et al. Significance of INHBA expression in human colorectal cancer[J]. Oncol Rep, 2013, 30(6): 2903-2908.
[8]	Grigoroiu M, Tagett R, Draghici S, et al. Gene-expression profiling in non-small cell lung cancer with invasion of mediastinal lymph nodes for prognosis evaluation[J]. Cancer Genomics Proteomics, 2015, 12(5):231-242.
[9]	Gao J, Xie L, Yang WS, et al. Risk factors of hepatocellular carcinoma--current status and perspectives[J]. Asian Pac J Cancer Prev, 2012, 13(3):743-752.
[10]	Fitzmaurice C, Akinyemiju TF，Al Lami FH, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global burden of disease study[J]. JAMA Oncol, 2018, 4(11):1553-1568.
[11]	Itoh S, Itoh F, Goumans MJ, et al. Signaling of transforming growth factor-beta family members through Smad proteins[J]. Eur J Biochem, 2000, 267(24):6954-6967.
[12]	Ling N, Ying SY, Ueno N, et al. Isolation and partial characterization of a Mr 32,000 protein with inhibin activity from porcine follicular fluid[J]. Proc Natl Acad Sci U S A, 1985, 82(21):7217-7221.
[13]	Shelling AN. Mutations in inhibin and activin genes associated with human disease[J]. Mol Cell Endocrinol, 2012, 359(1/2):113-120.
[14]	Stenvers KL, Findlay JK. Inhibins: from reproductive hormones to tumor suppressors[J]. Trends Endocrinol Metab, 2010, 21(3):174-180.
[15]	Howley BV, Hussey GS, Link LA, et al. Translational regulation of inhibin βA by TGFβ via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells[J]. Oncogene, 2016, 35(13):1725-1735.
[16]	Seder CW, Hartojo W, Lin L, et al. Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma[J]. Neoplasia, 2009, 11(4):388-396.
[17]	Singh P, Jenkins LM, Horst B, et al. Inhibin is a novel paracrine factor for tumor angiogenesis and metastasis[J]. Cancer Res, 2018, 78(11):2978-2989.
[18]	Seder CW, Hartojo W, Lin L, et al. INHBA overexpression promotes cell proliferation and may be epigenetically regulated in esophageal adenocarcinoma[J]. J Thorac Oncol, 2009, 4(4):455-462.
[19]	Okano M, Yamamoto H, Ohkuma H, et al. Significance of INHBA expression in human colorectal cancer[J]. Oncol Rep, 2013, 30(6): 2903-2908.
[20]	Katayama Y, Oshima T, Sakamaki K, et al. Clinical significance of INHBA gene expression in patients with gastric cancer who receive curative resection followed by adjuvant S-1 chemotherapy[J]. In Vivo, 2017, 31(4):565-571.
[21]	罗方, 李娜, 方贤磊, 等. 宫颈癌相关差异表达基因的筛选及预后价值分析[J]. 临床检验杂志, 2019, 37(8):633-637.
[22]	Li X, Yang Z，Xu S, et al. Targeting INHBA in ovarian cancer cells suppresses cancer xenograft growth by attenuating stromal fibroblast activation[J]. Dis Markers, 2019:7275289.
[23]	Hofland J, van Weerden WM, Steenbergen J, et al. Activin A stimulates AKR1C3 expression and growth in human prostate cancer[J]. Endocrinology, 2012, 153(12):5726-5734.
[24]	Lee HY, Li CC, Huang CN, et al. INHBA overexpression indicates poor prognosis in urothelial carcinoma of urinary bladder and upper tract[J]. J Surg Oncol, 2015, 111(4):414-422.

参数		例数	低表达	高表达	χ²值	P值
性别					0.724	0.395
	男	74	44	30
	女	7	3	4
年龄（岁）					1.279	0.258
	≥60	22	15	7
	<60	59	32	27
肝炎					1.667	0.197
	HBV/HCV	69	38	31
	无	12	9	3
肿瘤分化程度					15.499	0.000
	高分化	16	12	4
	中分化	50	33	17
	低分化	15	2	13
肝硬化					0.269	0.604
	有	62	35	27
	无	19	12	7
肿瘤直径（cm）					0.732	0.392
	≥5	36	19	17
	<5	45	28	17
血清AFP水平（μg/L）					0.027	0.870
	≤400	53	31	22
	>400	28	17	11
AJCC分期					9.100	0.011
	Ⅰ期	20	15	5
	Ⅱ期	33	22	11
	Ⅲ期	28	10	18

参数		例数	低表达	高表达	χ²值	P值
性别					0.724	0.395
	男	74	44	30
	女	7	3	4
年龄（岁）					1.279	0.258
	≥60	22	15	7
	<60	59	32	27
肝炎					1.667	0.197
	HBV/HCV	69	38	31
	无	12	9	3
肿瘤分化程度					15.499	0.000
	高分化	16	12	4
	中分化	50	33	17
	低分化	15	2	13
肝硬化					0.269	0.604
	有	62	35	27
	无	19	12	7
肿瘤直径（cm）					0.732	0.392
	≥5	36	19	17
	<5	45	28	17
血清AFP水平（μg/L）					0.027	0.870
	≤400	53	31	22
	>400	28	17	11
AJCC分期					9.100	0.011
	Ⅰ期	20	15	5
	Ⅱ期	33	22	11
	Ⅲ期	28	10	18

参数		单因素分析			多因素分析
参数		HR	95%CI	P	HR	95%CI	P
INHBA表达
	低表达	参考值	-	-	参考值	-	-
	高表达	2.771	1.317~5.830	0.007	2.612	1.195~5.706	0.016
AJCC分期
	Ⅰ期	参考值	-	-	参考值	-	-
	Ⅱ期	1.697	0.531~5.420	0.372	-	-	-
	Ⅲ期	5.744	1.970~16.925	0.001	4.316	1.423~13.086	0.010

参数		单因素分析			多因素分析
参数		HR	95%CI	P	HR	95%CI	P
INHBA表达
	低表达	参考值	-	-	参考值	-	-
	高表达	2.771	1.317~5.830	0.007	2.612	1.195~5.706	0.016
AJCC分期
	Ⅰ期	参考值	-	-	参考值	-	-
	Ⅱ期	1.697	0.531~5.420	0.372	-	-	-
	Ⅲ期	5.744	1.970~16.925	0.001	4.316	1.423~13.086	0.010

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