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Signal Transduct Target Ther. 2022 Jan 20;7(1):19. doi: 10.1038/s41392-021-00820-z.
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通过生物信息学和细胞模型分析,抑制ITGB1-DT表达可延缓胃腺癌的生长和迁移,并改善癌症患者的预后。

Inhibition of ITGB1-DT expression delays the growth and migration of stomach adenocarcinoma and improves the prognosis of cancer patients using the bioinformatics and cell model analysis.

作者信息

Jiang Ni, Guo Qiang, Luo Qing

机构信息

Cancer Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

出版信息

J Gastrointest Oncol. 2022 Apr;13(2):615-629. doi: 10.21037/jgo-22-233.

DOI:10.21037/jgo-22-233
PMID:35557569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9086027/
Abstract

BACKGROUND

The long non-coding RNA, integrin subunit beta 1 (ITGB1) divergent transcript (ITGB1-DT), is known to be involved in cancer progression and associated with the poor prognosis of cancer patients. At present, the role of ITGB1-DT in stomach adenocarcinoma (STAD) has not been reported.

METHODS

The expression level of ITGB1-DT was detected in normal gastric and STAD tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. A receiver operating characteristic (ROC) analysis was used to evaluate the role of ITGB1-DT in diagnosing STAD. The relationship between ITGB1-DT overexpression and clinicopathological features, prognosis, and immune-infiltrated cells in STAD were explored using correlation, survival, and Cox regression analyses. A cell model of ITGB1-DT interference was constructed to explore the roles of ITGB1-DT on STAD cell proliferation and migration, and the signaling mechanism was investigated using Gene Set Enrichment Analysis (GSEA).

RESULTS

ITGB1-DT was expressed up-regulated in STAD tissues. ITGB1-DT overexpression was associated with the T stage, therapeutic effect, overall survival, progression-free interval status, and poor prognosis in STAD patients. ITGB1-DT overexpression was valuable in diagnosing STAD and a negative factor affecting the prognosis of STAD patients. Interference with ITGB1-DT expression inhibited STAD cell proliferation, invasion, and migration. GSEA results showed that ITGB1-DT may be involved in STAD progression through the insulin, p53, mechanistic target of rapamycin kinase (MTOR), and other signaling pathways. Overexpression of ITGB1-DT was significantly correlated with the levels of STAD B cells, T cells, T helper cells, CD8 T cells, cytotoxic cells, and other immune cells.

CONCLUSIONS

ITGB1-DT was overexpressed and associated with poor prognosis in STAD. Interference with ITGB1-DT expression may delay the progression of STAD to improve the prognosis of STAD patients.

摘要

背景

长链非编码RNA,整合素亚基β1(ITGB1)差异转录本(ITGB1-DT),已知参与癌症进展并与癌症患者的不良预后相关。目前,ITGB1-DT在胃腺癌(STAD)中的作用尚未见报道。

方法

从癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库中检测正常胃组织和STAD组织中ITGB1-DT的表达水平。采用受试者工作特征(ROC)分析评估ITGB1-DT在诊断STAD中的作用。利用相关性分析、生存分析和Cox回归分析探讨ITGB1-DT过表达与STAD临床病理特征、预后及免疫浸润细胞之间的关系。构建ITGB1-DT干扰细胞模型,探讨ITGB1-DT对STAD细胞增殖和迁移的作用,并通过基因集富集分析(GSEA)研究其信号传导机制。

结果

ITGB1-DT在STAD组织中表达上调。ITGB1-DT过表达与STAD患者的T分期、治疗效果、总生存期、无进展生存期状态及不良预后相关。ITGB1-DT过表达对STAD诊断有价值,且是影响STAD患者预后的负性因素。干扰ITGB1-DT表达可抑制STAD细胞增殖、侵袭和迁移。GSEA结果显示,ITGB1-DT可能通过胰岛素、p53、雷帕霉素激酶机制性靶点(MTOR)等信号通路参与STAD进展。ITGB1-DT过表达与STAD B细胞、T细胞、辅助性T细胞、CD8 T细胞、细胞毒性细胞等免疫细胞水平显著相关。

结论

ITGB1-DT在STAD中过表达且与不良预后相关。干扰ITGB1-DT表达可能延缓STAD进展,改善STAD患者预后。