高表达MYO1B促进胃癌细胞增殖、迁移和侵袭并与患者的不良预后有关

doi:10.12122/j.issn.1673-4254.2025.03.20

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (3): 622-631.doi: 10.12122/j.issn.1673-4254.2025.03.20

• • 上一篇

高表达MYO1B促进胃癌细胞增殖、迁移和侵袭并与患者的不良预后有关

黄晴晴¹(), 张文静¹, 张小凤¹^,⁴, 王炼²^,⁴, 宋雪³^,⁴, 耿志军³^,⁴, 左芦根²^,⁴, 王月月¹^,⁴, 李静¹^,⁴, 胡建国¹^,⁴()

^1.蚌埠医科大学第一附属医院，检验科，安徽蚌埠 233004
^2.蚌埠医科大学第一附属医院，胃肠外科，安徽蚌埠 233004
^3.蚌埠医科大学第一附属医院，中心实验室，安徽蚌埠 233004
^4.蚌埠医科大学第一附属医院，炎症相关性疾病基础与转化研究安徽省重点实验室，安徽蚌埠 233004

收稿日期:2024-10-08 出版日期:2025-03-20 发布日期:2025-03-28
通讯作者: 胡建国 E-mail:hqq10100@163.com;jghu9200@bbmc.edu.cn
作者简介:黄晴晴，在读硕士研究生，E-mail: hqq10100@163.com
基金资助:
安徽省高校协同创新项目(GXXT-2020-020);蚌埠医科大学第一附属医院高水平科技创新团队(BYYFY2022TD002);安徽省高校优秀科研创新团队项目(2023AH010067);蚌埠医科大学临床研究专项(2022byflc011)

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

Qingqing HUANG¹(), Wenjing ZHANG¹, Xiaofeng ZHANG¹^,⁴, Lian WANG²^,⁴, Xue SONG³^,⁴, Zhijun GENG³^,⁴, Lugen ZUO²^,⁴, Yueyue WANG¹^,⁴, Jing LI¹^,⁴, Jianguo HU¹^,⁴()

^1.Clinical Laboratory, the First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China
^2.Department of Gastrointestinal surgery, the First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China
^3.Central Laboratory, the First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China
^4.Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu 233004, China

Received:2024-10-08 Online:2025-03-20 Published:2025-03-28
Contact: Jianguo HU E-mail:hqq10100@163.com;jghu9200@bbmc.edu.cn

摘要/Abstract

摘要：

目的明确肌球蛋白1B（MYO1B）在胃癌组织中的表达情况，并分析其对患者远期预后的评估价值以及对肿瘤细胞恶性生物学行为的影响和可能的机制。方法通过癌症公共数据库预测MYO1B在胃癌中的表达水平、与肿瘤分级、分期的相关性及对患者生存情况的影响。纳入在我院接受胃癌根治术的患者105例，采用免疫组化技术检测MYO1B在胃癌和癌旁组织中的表达情况，分析其与胃癌恶性进展参数的关系，以及对患者术后5年生存率的影响和评估价值。通过GO和KEGG富集分析MYO1B可能作用于胃癌的生物学功能和途径。体外探究MYO1B差异表达对胃癌细胞增殖、迁移和侵袭的作用及机制。结果癌症公共数据库显示胃癌组织中MYO1B表达水平高于正常组织，与肿瘤分级和分期有关并影响患者预后（P<0.05）。MYO1B在胃癌组织中高表达且与Ki67表达正相关（r=0.689，P<0.05）。MYO1B高表达与胃癌恶性进展参数（CEA≥5 μg/L、CA19-9≥37 kU/L、G3~4、T3~4及N2~3）相关（P<0.05）。Kaplan-Meier生存分析和多因素Cox回归显示，MYO1B高表达降低患者术后5年生存率且为独立危险因素（HR：3.522，95%CI：1.783~6.985，P<0.05）。ROC曲线反映，MYO1B表达水平对患者术后生存情况的预测能力较强（Cut off value：3.11，AUC：0.753，P<0.05）。MYO1B可能与细胞迁移和mTOR信号通路的调控有关（P<0.05）。上调MYO1B促进胃癌细胞增殖、迁移和侵袭能力（P<0.05）。体外过表达MYO1B可促进信号分子Akt、mTOR的磷酸化（P<0.05）。结论 MYO1B高表达可显著促进胃癌细胞增殖、迁移和侵袭，且与患者预后不良有关。

关键词: 胃癌, MYO1B, 预后, 增殖

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

黄晴晴, 张文静, 张小凤, 王炼, 宋雪, 耿志军, 左芦根, 王月月, 李静, 胡建国. 高表达MYO1B促进胃癌细胞增殖、迁移和侵袭并与患者的不良预后有关[J]. 南方医科大学学报, 2025, 45(3): 622-631.

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.

图/表 11

图1 MYO1B在胃癌组织中高表达且与肿瘤增殖活动有关

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.

图2 MYO1B高表达与胃癌患者肿瘤分级、分期显著相关

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.

表1 胃癌组织中MYO1B表达水平与胃癌恶性进展参数间的关系

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

图3 MYO1B高表达对胃癌患者术后5年生存情况的影响

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.

图4 MYO1B高表达预判胃癌患者术后5年生存情况

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

图5 MYO1B的KEGG和GO分析

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

图6 MYO1B在胃癌细胞中高表达

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.

图7 MYO1B高表达促进胃癌细胞增殖

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.

图8 MYO1B高表达促进胃癌细胞迁移和侵袭

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.

图9 MYO1B高表达可能激活Akt/mTOR通路

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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高表达MYO1B促进胃癌细胞增殖、迁移和侵袭并与患者的不良预后有关

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

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