研究动态
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P53 相关 lncRNA 调节胃癌中的免疫功能和 RNA 修饰剂。

P53-associated lncRNAs regulate immune functions and RNA-modifiers in gastric cancer.

发表日期:2024 Aug 15
作者: Zhao Huanjie, Ihtisham Bukhari, Li Fazhan, Huijuan Wen, Jingyun Wang, Wu Wanqing, Fu Yuming, Tang Youcai, Reem M AlJowaie, Ibrahim M Aziz, Chu Xiufeng, Mi Yang, Zheng Pengyuan
来源: Immunity & Ageing

摘要:

TP53是基因组的守护者,通过各种调节途径抑制或增强肿瘤。然而,p53相关的长非编码RNA(lncRNA)在肿瘤微环境的免疫调节和胃癌(GC)预后中的作用尚未阐明。我们分析了TP53相关lncRNA(从TP53LNC-DB数据库获得)在胃癌免疫调节、免疫细胞浸润和RNA修饰中的作用。首先,利用多变量COX回归分析,我们鉴定了8​​个与GC预后相关的lncRNA。此外,根据lncRNA特征的表达和风险评分,将GC患者分为高风险组和低风险组。我们发现,M2-巨噬细胞在高危人群中的浸润明显较高。同样,两组之间的免疫功能(APC_co_stimulation、CCR 和检查点)和 m6A 修饰(FTO、ZC3H13、YTHDC1 和 RBM15)以及 m5C 修饰(NOP2 和 TET1)也观察到显着差异。这些标志性 lncRNA 还与氧化应激相关基因(MPO、MAPK14、HMOX1 和 APP)呈正相关。此外,我们发现幽门螺杆菌(H-pylori)阳性GC患者中GAS5高表达,MALAT1低表达。最后,低风险组的GC患者对免疫治疗表现出较高的抵抗力,而高风险组的患者对各种化疗药物更敏感。基于这些发现,我们得出结论,p53 相关的 lncRNA 特征可以潜在地预测免疫状态和总体生存率,也可以用于胃癌患者的风险管理和免疫治疗规划。© 2024 作者。
TP53, a guardian of the genome, suppresses or enhances tumors through various regulatory pathways. However, the role of p53-related long non-coding RNAs (lncRNAs) in immune regulation of tumor microenvironment and prognosis of gastric cancer (GC) is so far unelucidated. We analyzed the role of TP53-associated lncRNAs (obtained from the TP53LNC-DB database) in immune regulation, immune cell infiltration and RNA modification in gastric cancer. Firstly, using multivariate COX regression analysis, we identified eight lncRNAs related to the prognosis of GC. Furthermore, based on the expression of the lncRNA signature and risk score, the GC patients were divided into high-risk and low-risk groups. We found that M2-macrophages have significantly higher infiltration in the high-risk group. Similarly, significant differences in immune function (APC_co_stimulation, CCR, and checkpoint) and m6A modification (FTO, ZC3H13, YTHDC1, and RBM15), and m5C modification (NOP2 and TET1) between both groups were also observed. These signature lncRNAs were also positively associated with oxidative stress-related genes (MPO, MAPK14, HMOX1, and APP). Additionally, we found that high expression of GAS5 and low expression of MALAT1 in Helicobacter pylori (H-pylori) positive GC patients. Finally, GC patients in the low-risk group showed higher resistance to immunotherapy while patients in the high-risk group were more sensitive to various chemotherapy drugs. Based on these findings, we conclude that p53-associated lncRNAs signature could potentially predict the immune status and overall survival, and may also be used for risk management and planning immunotherapy for gastric cancer patients.© 2024 The Authors.