High expression of MPP6 predicts poor patient prognosis and promotes malignant biological behaviors of hepatocellular carcinoma cells

doi:10.12122/j.issn.1673-4254.2026.02.17

Abstract

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

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.

Figures/Tables 8

References 28

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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

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

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

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

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