将 TLL2 作为与肺腺癌免疫浸润相关的潜在新预后生物标记物的综合分析和实验验证

Jing Jiang, Zhongye Du, Haijuan Tang, Yingying Huang, Dongbing Li, Qiuli Liang
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引用次数: 0

摘要

背景:在肺腺癌(LUAD)的背景下,类甲状腺球蛋白2(TLL2)的确切功能仍不确定:本研究的主要目的是进行全面分析:为了评估其诊断效用,研究人员使用了癌症基因组图谱(TCGA)数据库中的数据来评估TLL2在泛癌症和LUAD中的表达。研究还调查了 TLL2 表达水平与 LUAD 症状和预后之间的相关性。此外,研究还探讨了涉及 TLL2 的可能调控网络,包括其与免疫浸润、肿瘤干性指数(mRNAsi)和 LUAD 药物敏感性的关联。我们探讨了 TLL2 在 LUAD 单细胞测序中的表达,以及 TLL2 在 LUAD 中的基因组变异和临床意义。通过实时定量 PCR(qRT-PCR)技术验证了 TLL2 在 GSE87340 和细胞系中的表达:结果:在泛癌和 LUAD 中发现了 TLL2 的异常表达。在 LUAD 患者中,TLL2 水平的升高与 T 分期(p = 0.046)和病理分期(p = 0.016)显著相关。TLL2在LUAD患者中的表达与较差的总生存期(OS)明显相关(p < 0.001)。TLL2的表达被确定为较差OS的独立预测因子(p = 0.042)。TLL2与核糖体、神经活性配体-受体相互作用、异体移植排斥反应、ECM受体相互作用、哮喘、卟啉和叶绿素代谢、病灶粘附、戊糖和葡萄糖醛酸相互转化以及抗坏血酸和醛酸代谢有关。TLL2 在 LUAD 中的表达与免疫浸润和 mRNAsi 相关。在 LUAD 中,TLL2 的表达与 TAK-715、XMD13-2、STF-62247、OSI-930 和 EHT-1864 呈显著负相关。在多个 LUAD 细胞中,TLL2 基因被上调。与TLL2基因未发生改变的LUAD患者相比,TLL2基因发生改变的LUAD患者的PFS较短。TLL2在LUAD细胞中的表达明显增加:结论:对于 LUAD 患者,TLL2 可作为免疫治疗靶点和有用的预后生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive Analysis and Experimental Validation of TLL2 as a Potential New Prognostic Biomarker Associated with Immune Infiltration in Lung Adenocarcinoma.

Background: The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD).

Objective: The primary objective of this investigation was to conduct a thorough analysis.

Methods: To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR).

Results: An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage (p = 0.046) and the pathological stage (p = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) (p < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS (p = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up- -regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells.

Conclusion: For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker.

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