肝细胞癌中MPP6高表达预测患者不良预后并促进肿瘤恶性生物学行为

doi:10.12122/j.issn.1673-4254.2026.02.17

摘要/Abstract

摘要：

目的明确膜棕榈酰化蛋白6（MPP6）在肝细胞癌（HCC）中的表达，分析其表达与HCC患者临床病理特征和预后的关系，探讨其对HCC细胞生物学行为的影响。方法选取2017年1月~2019年12月在我院行手术治疗的118例HCC患者肿瘤及癌旁组织标本，收集患者的临床病理资料，随访患者总生存期。采用免疫组化分析MPP6在肿瘤和癌旁组织中的表达水平；采用Cox回归分析MPP6表达水平与HCC患者临床病理特征和患者总生存期的相关性；采用平板克隆、划痕实验、Transwell实验和流式细胞术检测MPP6对HCC细胞Hep3B生物学行为的影响。结果与癌旁组织相比，MPP6在HCC组织中高表达（P<0.001）；MPP6表达水平与患者肝硬化背景（P=0.028）和基线白蛋白水平（P=0.035）相关；生存分析提示，高表达MPP6患者预后较差（P<0.001）；Cox回归分析显示，MPP6表达水平是患者总生存期的独立预测因素（P=0.012，HR：2.335，95% CI： 1.502~3.629）。体外敲减MPP6可致Hep3B细胞增殖、迁移及侵袭能力下降（P<0.05），并阻滞细胞周期于G0/G1期（P<0.001）。结论 MPP6在HCC组织中高表达，并与HCC患者重要临床病理特征、不良预后相关；体外敲减MPP6可抑制HCC细胞增殖、迁移和侵袭能力并阻滞细胞周期于G0/G1期。

关键词: 肝细胞癌, 膜棕榈酰化蛋白6, 预后, 恶性生物学行为

Abstract:

Objective To investigate the expression of membrane protein palmitoylated 6 (MPP6) in hepatocellular carcinoma (HCC) and analyze its correlation with clinicopathological features and patient prognosis and its impact on biological behaviors of HCC cells. Methods We examined MPP6 expressions using immunohistochemistry in tumor and adjacent tissues from 118 HCC patients undergoing surgeries in our hospital from January, 2017 to December, 2019, and analyzed the correlation of MPP6 expression levels with clinicopathological data and overall survival (OS) of the patients using Cox regression analysis. In human hepatoma Hep3B cells, the effects of lentivirus-mediated MPP6 knockdown on biological behaviors of the cells were evaluated using colony formation assay, wound-healing assay, Transwell assay and flow cytometry. Results Compared with adjacent tissues, HCC tissues showed significant overexpression of MPP6 (P<0.001), whose expression levels was correlated with liver cirrhosis (P=0.028) and baseline albumin level (P=0.035) of the patients. Survival analysis suggested that HCC patients with a high expression of MPP6 had a worse prognosis (P<0.001); Cox regression analysis indicated that MPP6 expression (P=0.012, HR: 2.335, 95% CI: 1.502-3.629) was an independent predictor of OS of HCC patients following hepatectomy. In Hep3B cells, MPP6 knockdown obviously inhibited cell proliferation, migration and invasion (P<0.05) and caused cell cycle arrest in G0/G1 phase (P<0.001). Conclusion MPP6 is highly expressed in HCC tissues and correlates with important clinicopathological features and unfavorable prognosis of the patients. MPP6 knockdown inhibits proliferation, migration and invasion and blocks cell cycle progression in G0/G1 phase.

Key words: hepatocellular?carcinoma, membrane protein palmitoylated 6, prognosis, malignant biological behaviors

余晖豪, 邵玉, 程倩倩, 周新瑞, 耿海萍, 杨燕. 肝细胞癌中MPP6高表达预测患者不良预后并促进肿瘤恶性生物学行为[J]. 南方医科大学学报, 2026, 46(2): 394-402.

Huihao YU, Yu SHAO, Qianqian CHENG, Xinrui ZHOU, Haiping GENG, Yan YANG. High expression of MPP6 predicts poor patient prognosis and promotes malignant biological behaviors of hepatocellular carcinoma cells[J]. Journal of Southern Medical University, 2026, 46(2): 394-402.

图/表 8

图1 MPP6在HCC组织中的表达情况

Fig.1 Expression of MPP6 in HCC tissues. A: Representative images of differential expression of MPP6 in HCC and ANT tissues. B: Differential expressions of MPP6 in 118 HCC tissues and 59 ANT tissues. C: Differential expressions of MPP6 in 59 pairs of HCC and ANT tissues. ***P<0.001 vs ANT.

表1 MPP6表达与HCC患者临床病理特征的相关性分析

Tab.1 Correlation analysis between MPP6 expression and clinicopathological features of HCC patients

Factor	n	Low MPP6 expression	High MPP6 expression	P
Age (year)
≤60	75	29 (38.7%)	46 (61.3%)	0.557
>60	43	19 (44.2%)	24 (55.8%)	0.557
Gender
Female	24	12 (50.0%)	12 (50.0%)	0.298
Male	94	36 (38.3%)	58 (61.7%)	0.298
Hepatic sclerosis
No	23	14 (60.9%)	9 (39.1%)	0.028
Yes	95	34 (35.8%)	61 (64.2%)	0.028
Child-Pugh
A	109	42 (38.5%)	67 (61.5%)	0.156
B	9	6 (66.7%)	3 (33.3%)	0.156
Alpha-fetoprotei (ng/mL)^#
≤20	53	19 (35.8%)	34 (64.2%)	0.348
>20	63	28 (44.4%)	35 (55.6%)	0.348
Alanine aminotransferase (U/L)
≤45	92	35 (38.0%)	57 (62.0%)	0.273
>45	26	13 (50.0%)	13 (50.0%)	0.273
Glutamyltransferase (U/L)
≤45	61	28 (45.9%)	33 (54.1%)	0.232
>45	57	20 (35.1%)	37 (64.9%)	0.232
Albumin (mg/L)
≤40	55	28 (50.9%)	27 (49.1%)	0.035
>40	63	20 (31.7%)	43 (68.3%)	0.035
Tumor size (cm)
≤5	65	29 (44.6%)	36 (55.4%)	0.335
>5	53	19 (35.8%)	34 (64.2%)	0.335
Tumor number
Single	98	40 (40.8%)	58 (59.2%)	0.628
Multiple	20	8 (40.0%)	12 (60.0%)	0.628
Tumor capsule
Complete	3	1 (33.3%)	2 (66.7%)	0.793
Incomplete	115	47 (40.9%)	68 (59.1%)	0.793
Portal vein branch tumor thrombus
Yes	5	1 (20.0%)	4 (80.0%)	0.336
No	113	47 (41.6%)	66 (58.4%)	0.336
BCLC staging
0-A	49	24 (49.0%)	25 (51.0%)	0.127
B-C	69	23 (33.3%)	46 (66.7%)	0.127

图2 MPP6不同表达水平下HCC患者的OS生存曲线

Fig.2 Survival curve for overall survival (OS) of HCC patients with low and high MPP6 expression levels.

表2 HCC术后患者OS预后因素的单因素Cox回归分析

Tab.2 Univariate Cox regression analysis of prognostic factors for OS in postoperative HCC patients

Factor	n	HR	95%CI	P
Age (year)
≤60	75	1.404	0.932-2.114	0.105
>60	43	1.404	0.932-2.114	0.105
Gender
Female	24	1.027	0.621-1.697	0.919
Male	94	1.027	0.621-1.697
Hepatic sclerosis
No	23	0.769	0.471-1.257	0.295
Yes	95	0.769	0.471-1.257
Child-Pugh
A	109	0.925	0.448-1.912	0.834
B	9	0.925	0.448-1.912
Alpha-fetoprotei (ng/mL)^#
≤20	53	0.746	0.500-1.113	0.151
>20	63	0.746	0.500-1.113	0.151
Alanine aminotransferase (U/L)
≤45	92	1.441	0.909-2.287	0.120
>45	26	1.441	0.909-2.287	0.120
Glutamyltransferase (U/L)
≤45	61	1.464	0.983-2.180	0.061
>45	57	1.464	0.983-2.180	0.061
Albumin (mg/L)
≤40	55	1.064	0.712-1.591	0.761
>40	63	1.064	0.712-1.591	0.761
Tumor size (cm)
≤5	65	1.578	1.062-2.346	0.024
>5	53	1.578	1.062-2.346	0.024
Tumor number
Single	98	1.297	0.786-2.140	0.309
Multiple	20	1.297	0.786-2.140	0.309
Tumor capsule
Complete	3	2.083	0.655-6.623	0.214
Incomplete	115	2.083	0.655-6.623	0.214
Portal vein branch tumor thrombus
Yes	5	2.437	0.985-6.028	0.054
No	113	2.437	0.985-6.028	0.054
BCLC staging
0-A	49	1.497	0.995-2.251	0.053
B-C	64	1.497	0.995-2.251	0.053
Postoperative treatment
No	42	0.771	0.511-1.612	0.214
Yes	76	0.771	0.511-1.612	0.214
MPP6 Expression
Low	48	2.450	1.584-3.788	<0.001
High	70

表3 HCC术后患者OS预后因素的多因素Cox回归分析

Tab.3 Multivariate Cox regression analysis of prognostic factors for OS in postoperative HCC patients

Factor	n	HR	95% CI	P
Tumor size (cm)
≤5	65	1.405	0.941-2.098	0.096
>5	53	1.405	0.941-2.098	0.096
MPP6 Expression
Low	48	2.335	1.502-3.629	0.012
High	70	2.335	1.502-3.629	0.012

图3 敲减MPP6基因的Hep3B细胞筛选与构建

Fig.3 HCC cell screening and construction of Hep3B cells with MPP6 gene knockdown. A: Western blotting for detecting expression level of MPP6 in different HCC cell lines (*P<0.05, **P<0.01, ***P<0.001 vs LO2 cells). B: Western blotting for assessing efficiency of MPP6 gene knockdown in Hep3B cells (***P<0.001 vs sh NC).

图4 敲减MPP6基因对Hep3B细胞增殖、迁移和侵袭的影响

Fig.4 Effect of MPP6 knockdown on proliferation, migration and invasion of Hep3B cells. A: Colony formation assay for assessing cell proliferation following MPP6 knockdown. B: Wound-healing assay for assessing migration ability of Hep3B cells with MPP6 knockdown (Original magnification: ×40). C: Transwell assay for assessing migration and invasion capabilities of Hep3B cells with MPP6 knockdown (×100). *P<0.05, **P<0.01, ***P<0.001 vs sh NC.

图5 　敲减MPP6基因对Hep3B细胞周期分布的影响

Fig.5 　Effect of MPP6 knockdown on cell cycle distribution of Hep3B cells. A: Flow cytometry for assessing the impact ofMPP6 knockdown on cell cycle distribution of Hep3B cells. B: Quantitative analysis of cell cycle distribution in Hep3Bcells. ***P<0.001 vs sh NC.

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