Wei Yamin, Wei Shanwang, Lei Zhongteng, Zhang Yan, Wu Jinxiao, Huang Jinli, Fu Lijuan, Li Zhimeng, Huang Guiying, Liang Yuanna, Zheng Jinhua
Department of Pathology, Affiliated Hospital, Guilin Medical University, Guilin, 541001, China.
Clinical School of Medicine, Qinghai University, Xining, 810000, China.
Sci Rep. 2025 Apr 1;15(1):11096. doi: 10.1038/s41598-025-89377-3.
Research the expression of USP4 in lung adenocarcinoma and its correlation with clinicopathological features and prognosis analysis, to explore the invasion and metastasis mechanism of USP4 in lung adenocarcinoma, and to clarify the mechanism of USP4's involvement in the occurrence and development of lung adenocarcinoma. The expressions of USP4, VEGF, MMP2 and Ki67 in lung adenocarcinoma and adjacent tissues of 139 patients with lung adenocarcinoma were detected by immunohistochemical method, and the correlation between expression and clinicopathological features and survival curve were analyzed by statistical method. The expression of USP4 was interfered by LIP-2000 cell transfection technology, and the expression of USP4 and its related factors in protein level was detected by Western Blot, and their correlation was analyzed. After silencing USP4 expression, the effects of USP4 on proliferation, invasion and migration of lung adenocarcinoma cells were detected by cell scratches assay, MTT assay, Transwell assay and tumorigenesis assay in nude mice. The expression of USP4 in lung adenocarcinoma tissues was higher than that in normal adjacent tissues, and the high expression of USP4 was significantly correlated with the differentiation degree of lung adenocarcinoma, clinical stage and pathological grade lymph node metastasis. After silencing USP4 expression, the expression of cyclin apoptosis protein invasion related proteins and phosphorylation factors were affected, and then cell migration and the proliferation ability decreased, the number of invasion and metastasis decreased, and the tumor volume decreased in nude mice. USP4 may play a certain role in the invasion and metastasis of lung adenocarcinoma by regulating the expression of tumor-related factors and affecting the prognosis of patients with lung adenocarcinoma. USP4 can be used as a potential therapeutic target for clinical diagnosis of lung adenocarcinoma and provide a new opportunity for clinical research on lung adenocarcinoma.
研究USP4在肺腺癌中的表达及其与临床病理特征的相关性并进行预后分析，探讨USP4在肺腺癌中的侵袭和转移机制，阐明USP4参与肺腺癌发生发展的机制。采用免疫组化方法检测139例肺腺癌患者肺腺癌组织及癌旁组织中USP4、VEGF、MMP2和Ki67的表达，用统计学方法分析其表达与临床病理特征及生存曲线的相关性。采用LIP-2000细胞转染技术干扰USP4的表达，用Western Blot检测USP4及其相关因子的蛋白水平表达，并分析其相关性。沉默USP4表达后，通过细胞划痕实验、MTT实验、Transwell实验及裸鼠成瘤实验检测USP4对肺腺癌细胞增殖、侵袭和迁移的影响。USP4在肺腺癌组织中的表达高于正常癌旁组织，USP4高表达与肺腺癌的分化程度、临床分期、病理分级及淋巴结转移显著相关。沉默USP4表达后，细胞周期凋亡蛋白、侵袭相关蛋白及磷酸化因子的表达受到影响，进而细胞迁移和增殖能力下降，侵袭转移数量减少，裸鼠肿瘤体积减小。USP4可能通过调节肿瘤相关因子的表达在肺腺癌的侵袭转移中发挥一定作用，并影响肺腺癌患者的预后。USP4可作为肺腺癌临床诊断的潜在治疗靶点，为肺腺癌的临床研究提供新契机。
