lncRNA PVT1表达在胃癌预后评估及恶性进展中的作用:基于列线图模型与细胞功能实验的研究

doi:10.6040/j.issn.1671-7554.0.2025.0030

摘要/Abstract

摘要： 目的探讨基于长链非编码RNA浆细胞瘤变异易位1(long noncoding RNA plasmacytoma variant translocation 1, lncRNA PVT1)列线图模型预测胃癌(gastric cancer, GC)术后生存概率的价值,分析lncRNA PVT1对胃癌细胞增殖、侵袭能力的影响。方法采用实时荧光定量PCR(quantitative real-time polymerase chain reaction, RT-qPCR)法检测196例GC组织及配对癌旁正常胃黏膜组织中lncRNA PVT1和c-Myc表达水平,采用Western blotting法检测GC组织中c-Myc蛋白表达,并进行GC相关临床病理特征的生存分析和Cox回归分析,构建预后模型。以MGC-803细胞为研究对象,将转染siRNA-lncRNA PVT1组设为实验组,转染siRNA-NC组设为生理盐水对照组(siNC),空白对照组不进行任何转染,Western blotting检测GC细胞中c-Myc蛋白表达,通过CCK-8、Transwell实验检测GC细胞增殖、侵袭能力。结果 GC组织中lncRNA PVT1表达(P=0.002)、c-Myc mRNA表达(P=0.013)和蛋白表达(P=0.024)显著高于癌旁正常组织;单因素生存分析和多因素Cox回归分析显示,年龄(P=0.004)、Laurens 分型(P=0.021)、肿瘤局部浸润(P<0.001)、pTNM分期(P=0.020)、局部淋巴结转移(P=0.002)、lncRNA PVT1表达水平(P<0.001)与GC患者总生存期(overall survival, OS)显著相关,是其独立危险因素。基于lncRNA PVT1的列线图模型预测胃癌术后1年、2年、3年OS生存概率分别为0.997、0.937、0.828;敲减lncRNA PVT1后,与siNC组相比,siPVT1-1907组c-Myc mRNA(P<0.001)和蛋白表达(P=0.006)、细胞增殖(P<0.001)和侵袭能力(P=0.028)均显著降低。结论 lncRNA PVT1在胃癌中高表达,并与患者预后显著相关。基于lncRNA PVT1的列线图模型对胃癌术后生存概率具有较好的预测能力。lncRNA PVT1通过促进胃癌细胞Myc的表达而发挥致癌作用,高表达的lncRNA PVT1具有促进胃癌细胞增殖、侵袭的作用,提示lncRNA PVT1-Myc调控网络可能成为胃癌临床治疗的新靶点。

关键词: 浆细胞瘤变异易位1, 胃癌, 预后, 列线图, 癌基因Myc, RNA干扰

Abstract: Objective To explore the prognostic value of the long noncoding RNA plasmacytoma variant translocation 1(lncRNA PVT1)nomogram model in predicting postoperative survival in patients with gastric cancer(GC), and to investigate the effects of lncRNA PVT1 on the proliferation and invasion of GC cells. Methods A quantitative real-time polymerase chain reaction(RT-qPCR)was employed to measure the expression levels of lncRNA PVT1 and c-Myc in GC tissues and paired gastric mucosa tissues from 196 patients. The expression of c-Myc protein in GC tissues was detected using the western blotting technique. The investigation involved the implementation of survival analysis and Cox regression analysis, with the objective of elucidating the clinicopathological factors associated with GC and the construction of a prognostic model. In vitro, MGC-803 cells were subjected to transfection with a specific interfering RNA(siRNA)designed to target lncRNA PVT1. The experimental design involved the establishment of three distinct groups: the experimental group, which received the targeted knockdown via the PVT1-siRNA, the control group, which received a non-specific negative control via the PVT1-siRNA, and a third group that served as a blank control, receiving no transfection. The expression of c-Myc protein in GC cells was measured using Western blotting, while cell proliferation and invasion were evaluated using CCK-8 and Transwell assays, respectively. Results The expression of lncRNA PVT1(P=0.002), along with c-Myc mRNA expression(P=0.013)and protein levels(P=0.024), was significantly elevated in GC tissues compared to adjacent normal tissues. Univariate survival analysis and multivariate Cox regression analysis identified several factors significantly correlated with overall survival(OS)in GC patients, including age(P=0.004), and Laurens classification(P=0.021). The following factors were found to be statistically significant: local tumor invasion(P<0.001), pTNM stage(P=0.020), local lymph node metastasis(P=0.002), and the expression level of lncRNA PVT1(P<0.001). The expression level of lncRNA PVT1 was found to be an independent risk factor. The nomogram model based on lncRNA PVT1 predicted 1-year, 2-year, and 3-year OS probabilities of 0.997, 0.937, and 0.828, respectively. Furthermore, following the silencing of lncRNA PVT1, a significant reduction in both c-Myc mRNA(P<0.001)and protein levels(P=0.006)was observed, as well as a reduction in cell proliferation(P<0.001)and invasion ability(P=0.028)in the siPVT1-1907 group compared to the siNC group. Conclusion The present study has showed that the expression of lncRNA PVT1 is elevated in cases of gastric cancer, and that this elevation is associated with a poor prognosis for patients. The lncRNA PVT1-based nomogram model demonstrates good predictive capability for postoperative survival in GC. Additionally, lncRNA PVT1 appears to promote carcinogenesis by upregulating c-Myc expression in GC cells. This finding indicates that the lncRNA PVT1-Myc regulatory network may represent a viable target for the clinical management of gastric cancer.

Key words: Plasmacytoma variant translocation 1, Gastric cancer, Prognosis, Nomogram, Oncogene Myc, RNA interference

中图分类号:

R735.2

陈文亮,王欢欢,郝金锦,弓蕊,赵强,张飞,高磊,董静逊. lncRNA PVT1表达在胃癌预后评估及恶性进展中的作用:基于列线图模型与细胞功能实验的研究[J]. 山东大学学报 (医学版), 2025, 63(10): 61-71.

CHEN Wenliang, WANG Huanhuan, HAO Jinjin, GONG Rui, ZHAO Qiang, ZHANG Fei, GAO Lei, DONG Jingxun. The role of lncRNA PVT1 in prognostic assessment and malignant progression of gastric cancer: a study based on nomogram model and functional cellular experiments[J]. Journal of Shandong University (Health Sciences), 2025, 63(10): 61-71.

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