PSMD11 overexpression promotes epithelial-mesenchymal transition in gastric cancer and affects patient prognosis

doi:10.12122/j.issn.1673-4254.2025.12.22

Abstract

Abstract:

Objective To investigate the expression of the 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) in gastric cancer and its impact on long-term patient prognosis. Methods Tumor and adjacent tissue samples were collected from a cohort of 94 gastric cancer patients treated at our hospital from January, 2016 to December, 2019. Immunohistochemistry was used to detect PSMD11 and Ki67 expression levels in the tissues, whose correlations with clinicopathological parameters and postoperative 5-year survival of the patients were analyzed. PSMD11 expression in gastric cancer was also analyzed using data from the GEPIA and UALCAN databases, while the KM-plotter database was used to predict 5-year survival rates. KEGG and GO enrichment analyses were employed to predict the biological functions and mechanisms of PSMD11. In cultured HGC-27 cells, the effects of PSMD11 knockdown and overexpression on cell migration, invasion and expressions of epithelial-mesenchymal transition (EMT) markers and TGF‑β/Smad pathway proteins were evaluated using scratch wound healing assay, Transwell assay, and Western blotting. Results Bioinformatic analysis showed that PSMD11 expression was significantly elevated in gastric cancer and positively correlated with Ki67 expression (r=0.73, P<0.05). Survival analysis suggested that high PSMD11 expression was correlated with a poorer prognosis in gastric cancer patients. Univariate and multivariate Cox regression analyses identified PSMD11 as an independent prognostic risk factor in gastric cancer (HR: 2.167, 95% CI: 1.159-4.051, P=0.015). Enrichment analysis suggested involvement of PSMD11 in EMT and TGF‑β signaling. In HGC-27 cells, PSMD11 overexpression significantly enhanced while PSMD11 knockdown suppressed cell migration and invasion. PSMD11 overexpression significantly increased the expression levels of vimentin, N-cadherin, TGF‑β, and p-Smad2/3 and reduced E-cadherin expression, and PSMD11 knockdown produced the opposite changes. Conclusion PSMD11 is overexpressed in gastric cancer and adversely affects patient prognosis likely by driving EMT via activation of the TGF-β/Smad signaling pathway.

Key words: PSMD11, gastric carcinoma, prognosis, epithelial-mesenchymal transition, TGF-β/Smad pathway

Renjie ZHOU, Jingjing YANG, Bowen SONG, Xiaohua CHEN, Lian WANG, Yueyue WANG, Lugen ZUO, Bing ZHU. PSMD11 overexpression promotes epithelial-mesenchymal transition in gastric cancer and affects patient prognosis[J]. Journal of Southern Medical University, 2025, 45(12): 2747-2755.

Figures/Tables 10

Fig.1 Expressions and correlation analysis of PSMD11 and Ki67 in gastric cancer tissues. A: Expression of PSMD11 in pan-cancer. B, C: Expression of PSMD11 in gastric cancer and adjacent tissues. D: Immunohistochemical staining of PSMD11 and Ki67. E, F: Relative IOD values of PSMD11 and Ki67. G: Correlation between PSMD11 and Ki67. *P<0.05, **P<0.01, ***P<0.001 vs Normal/Adjacent group.

Fig.2 Relationship between PSMD11 expression in gastric cancer tissues and clinicopathological parameters of the patients. A, B: Correlation of PSMD11 expression levels with tumor grades and stages. C: Correlation of PSMD11 expression level with lymph node metastasis of gastric cancer. *P<0.05, ***P<0.001 vs adjacent tissue.

Tab.1 Relationship between PSMD11 expression level in gastric cancer tissues and parameters of malignant progression in gastric cancer patients (n, %)

Characteristics	n	PSMD11 expression (n=47)		χ²	P
Characteristics	n	Low	High	χ²	P
Gender				0.048	0.826
Female	31	15 (48.39%)	16 (51.61%)
Male	63	32 (50.79%)	31 (49.21%)
Age (year)				0.048	0.826
<60	31	16 (51.61%)	15 (48.39%)
≥60	63	31 (49.21%)	32 (50.79%)
Pathohistological type				0.052	0.82
Adenocarcinoma	67	34 (50.75%)	33 (49.25%)
Other	27	13 (48.15%)	14 (51.85%)
CEA (μg/L)				13.155	<0.001
<5	35	26 (74.29%)	9 (25.71%)
≥5	59	21 (35.59%)	38 (64.41%)
CA19-9 (kU/L)				10.938	0.001
<37	44	30 (68.18%)	14 (31.82%)
≥37	50	17 (34%)	33 (66%)
Tumor size (cm)				1.549	0.213
<5	42	24 (57.14%)	18 (42.86%)
≥5	52	23 (44.23%)	29 (55.77%)
Histological Grading				4.257	0.039
G1-G2	46	28 (60.87%)	18 (39.13%)
G3-G4	48	19 (39.58%)	29 (60.42%)
T Stage				11.525	0.001
T1-T2	36	26 (72.22%)	10 (27.78%)
T3-T4	58	21 (36.21%)	37 (63.79%)
N Stage				11.141	0.001
N0-N1	40	28 (70%)	12 (30%)
N2-N3	54	19 (35.19%)	35 (64.81%)

Fig.3 Effect of PSMD11 on prognosis of patients with gastric cancer. A: Kaplan-Meier analysis. B: Survival curves. C: Predictive value of PSMD11 for 5-year postoperative survival in gastric cancer patients.

Fig.4 Univariate analysis and multifactorial Cox regression of survival of gastric cancer patients within 5 years after surgery.

Fig.5 KEGG and GO enrichment analyses of PSMD11 and gastric cancer co-expressed genes. A: KEGG enrichment analysis results. B: GO enrichment analysis results.

Fig.6 PSMD11 overexpression promotes migration and invasion of gastric cancer cells (Transwell assay). A-C: Lentivirus-mediated knockdown and overexpression of PSMD11 in HGC-27 cells. D-I: Migration and invasion of the transfected HGC-27 cells (n=3), Si: siRNA; LV: Overexpression. *P<0.05 vs Si-NC or LV-Control.

Fig.7 Wound healing assay showing that PSMD11 overexpression promotes migration and invasion of gastric cancer cells. A-C: PSMD11 overexpression promotes HGC-27 cell migration in Wound-Healing assay. n=3, Si: siRNA; LV: overexpression. *P<0.05 vs Si-NC or LV-Control.

Fig.8 PSMD11 promotes EMT process in gastric cancer cells. A-C: Expressions of key proteins of EMT in gastric cancer cells (n=3). Si: siRNA. *P<0.05 vs Si-NC or LV-Control.

Fig.9 Overexpression of PSMD11 in gastric cancer activates the TGF-β/Smad signaling pathway. A-C: Expressions of TGF-β1, p-Smad2/3, and Smad2/3 in HGC-27 cells. *P<0.05 vs Si-NC or LV-Control.

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