双硫死亡相关LncRNA在胃癌中的表达及其临床意义

doi:10.16139/j.1007-9610.2024.05.09

摘要/Abstract

摘要：

目的：建立基于双硫死亡相关长链非编码RNA（LncRNA）的评分模型并探索LncRNA-SNHG4促进胃癌进展的机制。方法：首先基于TCGA数据库分析胃癌中双硫死亡基因的多组学特征，进一步筛选双硫死亡相关的LncRNA（DRLncs），构建双硫死亡相关基因风险评估(DRG-RS)模型，预测胃癌病人的总生存(Overall survival, OS)及与临床特征之间的关联，分析高、低风险组之间差异基因、功能富集和化疗疗效的相关性。通过CCK-8实验和迁移实验检测证实LncRNA-SNHG4促进胃癌细胞的恶性表型。通过免疫印迹实验检测LncRNA-SNHG4调控的信号通路。结果：成功构建包含8种DRLncs的DRG-RS，其预测胃癌病人OS的表现良好。DRG-RS模型与肿瘤相关信号通路、胃癌病人临床特征和药物敏感性之间显著相关。LncRNA-SNHG4在胃癌组织中表达显著升高，LncRNA-SNHG4显著促进胃癌细胞的增殖和迁移能力，并激活胃癌细胞中Wnt信号通路。结论：本研究构建的DRG-RS模型可对胃癌预后进行分层，且与胃癌病人的恶性特征和化疗疗效密切相关。LncRNA-SNHG4在胃癌组织中表达明显升高，且LncRNA-SNHG4通过激活Wnt信号通路促进胃癌细胞的恶性表型，在胃癌进展中可能发挥重要作用。

关键词: 胃癌, 双硫死亡, 双硫死亡相关长链非编码RNA, 长链非编码RNA核仁小RNA宿主基因4, Wnt信号通路

Abstract:

Objective To construct prognostic model of disulfidptosis-related LncRNA (DRLncs) and explore the mechanism of LncRNA-small nucleolar RNA host genes（SNHG4） in promoting the progression of gastric cancer. Methods The multi-omics features of disulfidptosis genes in gastric cancer were first analyzed based on The Cancer Genome Atlas(TCGA) database. DRLncs were further screened, and disulfidptosis related gene recurrence score (DRG-RS) model was constructed to predict the overall survival(OS) and correlation with the clinical characteristics of gastric cancer patients. Differential gene analysis, functional enrichment and the correlation between chemotherapy efficacy in high- and low-risk groups were analyzed. Cell-counting kit-8 (CCK-8) assay and migration assay confirmed that LncRNA-SNHG4 promoted the malignant phenotype of gastric cancer cells. Western Blotting assay was used to detect the signaling pathway regulated by LncRNA-SNHG4. Results DRG-RS model including 8 DRLncs was successfully constructed, showing good performance in predicting OS of the patients with gastric cancer. DRG-RS model was significantly correlated with tumor-related signaling pathways, clinical characteristics and drug sensitivity of gastric cancer patients. LncRNA-SNHG4 expression was significantly increased in gastric cancer. LncRNA-SNHG4 promoted the proliferation and migration of gastric cancer cells. LncRNA-SNHG4 promoted the activation of Wnt signaling pathway in gastric cancer cells. Conclusions The DRG-RS model constructed in our study can stratify the prognosis of gastric cancer, and is closely related to malignant characteristics and chemotherapy efficacy of gastric cancer patients. The expression of LncRNA-SNHG4 significantly increased in gastric cancer tissues, and LncRNA-SNHG4 promoted the malignant phenotype of gastric cancer cells through the Wnt signaling pathway, suggesting that LncRNA-SNHG4 may play an important role in the progression of gastric cancer.

Key words: Gastric Cancer, Disulfidptosis, Disulfidptosis-related long non-coding RNA(LncRNA), LncRNA-small nucleolar RNA host gene (SNHG4), Wnt signaling pathway

中图分类号:

R735.2

褚玉丹, 孙海东, 崔冉, 郑鸿. 双硫死亡相关LncRNA在胃癌中的表达及其临床意义[J]. 外科理论与实践, 2024, 29(05): 414-425.

CHU Yudan, SUN Haidong, CUI Ran, ZHENG Hong. Expression and clinical significance of disulfidptosis-related LncRNA in gastric cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(05): 414-425.

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