High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is associated with poor patient prognosis

doi:10.12122/j.issn.1673-4254.2025.03.20

Abstract

Abstract:

Objective To analyze MYO1B expression in gastric cancer, its association with long-term prognosis and its role in regulating biological behaviors of gastric cancer cells. Methods We analyzed MYO1B expression in gastric cancer and its correlation with tumor grade, tumor stage, and patient survival using the Cancer Public Database. We also examined MYO1B expression with immunohistochemistry in gastric cancer and paired adjacent tissues from 105 patients receiving radical surgery and analyzed its correlation with cancer progression and postoperative 5-year survival of the patients. GO and KEGG enrichment analyses were used to explore the biological functions of MYO1B and the key pathways. In cultured gastric cancer cells, we examined the changes in cell proliferation, migration and invasion following MYO1B overexpression and knockdown. Results Data from the Cancer Public Database showed that MYO1B expression was significantly higher in gastric cancer tissues than in normal tissues with strong correlations with tumor grade, stage and patient prognosis (P<0.05). In the clinical tissue samples, MYO1B was significantly overexpressed in gastric cancer tissues in positive correlation with Ki67 expression (r=0.689, P<0.05) and the parameters indicative of gastric cancer progression (CEA ≥5 μg/L, CA19-9 ≥37 kU/L, G3-4, T3-4, and N2-3) (P<0.05). Kaplan-Meier analysis and multivariate Cox regression analysis suggested that high MYO1B expression was associated with decreased postoperative 5-year survival and was an independent risk factor (HR: 3.522, 95%CI: 1.783-6.985, P<0.05). MYO1B expression level was a strong predictor of postoperative survival (cut-off value: 3.11, AUC: 0.753, P<0.05). GO and KEGG analyses suggested that MYO1B may regulate cell migration and the mTOR signaling pathway. In cultured gastric cancer cells, MYO1B overexpression significantly enhanced cell proliferation, migration, and invasion and promoted the phosphorylation of Akt and mTOR. Conclusion High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is correlated with poor patient prognosis.

Key words: gastric cancer, MYO1B, prognosis, proliferation

Qingqing HUANG, Wenjing ZHANG, Xiaofeng ZHANG, Lian WANG, Xue SONG, Zhijun GENG, Lugen ZUO, Yueyue WANG, Jing LI, Jianguo HU. High MYO1B expression promotes proliferation, migration and invasion of gastric cancer cells and is associated with poor patient prognosis[J]. Journal of Southern Medical University, 2025, 45(3): 622-631.

Figures/Tables 11

Fig.1 MYO1B is highly expressed in gastric cancer tissues and is associated with tumor proliferation activity. A: Pan-cancer differential analysis from the TIMER database. B: Immunohistochemical staining (Markers: MYO1B and Ki67). C: Relative IOD value of MYO1B. D: Relative IOD value of Ki67. E: Pearson correlation analysis. *P<0.05 vs adjacent tissue.

Fig.2 High MYO1B expression is significantly correlated with tumor grading and staging in gastric cancer patients. A: Correlation between MYO1B expression (transcript per million, TPM) and tumor grading in gastric cancer. B: Correlation between MYO1B TPM and tumor staging in gastric cancer. **P<0.01, ***P<0.001 vs Normal.

Tab.1 Relationship between MYO1B expression level and parameters of cancer progression in gastric cancer patients

Characteristic	n	MYO1B		χ²	P
Characteristic	n	Low expression (n=52)	High expression (n=53)	χ²	P
Gender				0.232	0.630
Female	69	33	36
Male	36	19	17
Age (year)				1.144	0.285
<60	49	27	22
≥60	56	25	31
Pathohistological type				0.077	0.782
Adenocarcinoma	74	36	38
Other	31	16	15
CEA (μg/L)				9.258	0.002
<5	45	30	15
≥5	60	22	38
CA19-9 (kU/L)				11.675	<0.001
<37	49	33	16
≥37	56	19	37
Tumor size (cm)				1.153	0.283
<5	43	24	19
≥5	62	28	34
Histological grading				16.005	<0.001
G1-G2	52	36	16
G3-G4	53	16	37
T Stage				9.160	0.002
T1-T2	53	34	19
T3-T4	52	18	34
N Stage				9.155	0.002
N0-N1	49	32	17
N2-N3	56	20	36

Fig.3 Impact of high MYO1B expression on 5-year postoperative survival of gastric cancer patients and its prognostic value. A: Analysis from the Kaplan-Meier Plotter database. B: Kaplan-Meier analysis.

Fig.4 Receiver Operating Characteristic Curve showing that a high expression of MYO1B predicts poor 5-year survival of gastric cancer patients.

Fig.5 KEGG analysis and GO analysis of MYO1B. A: Gene Ontology enrichment analysis. B: Kyoto Encyclopedia of Genes and Genomes enrichment analysis.

Fig.6 MYO1B expressions are significantly higher in HGC-27 and AGS cells than in GES-1 cells detected by Western blotting (n=3). *P<0.05 vs GES-1.

Fig.7 High expression of MYO1B promotes proliferation of gastric cancer cells. A, B: Verification of MYO1B knockdown and overexpression in HGC-27 and AGS cells. C, D: High expression of MYO1B promotes proliferation of HGC-27 and AGS cells. n=3, *P<0.05 vs shNC or Vector.

Fig.8 Overexpression of MYO1B promotes migration and invasion of gastric cancer cells. A, B: Overexpression of MYO1B promotes HGC-27 cell migration and invasion. C, D: Overexpression of MYO1B promotes AGS cell migration and invasion. n=3, *P<0.05 vs shNC or Vector.

Fig.9 Overexpression of MYO1B may activate the Akt/mTOR pathway. A, B: MYO1B overexpression significantly enhances phosphorylation of Akt and mTOR in HGC-27 cells. n=3, *P<0.05 vs Vector.

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