Chen Leyan, Qi Tuoya, Zhang Bishu, Wang Xuelong, Zheng Mingfeng
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
Sci Rep. 2025 Feb 5;15(1):4340. doi: 10.1038/s41598-025-88964-8.
Lung adenocarcinoma (LUAD), the most common type of lung cancer, is a leading cause of cancer-related mortality. NT5E, an ecto-5'-nucleotidase enzyme, has been implicated in cancer progression, particularly in efferocytosis. Despite its potential involvement, the prognostic significance of NT5E and relationship with immune cell infiltration in LUAD have not been extensively explored. In this study, we performed a comprehensive analysis to elucidate the expression patterns of NT5E and its prognostic implications in LUAD using data from diverse public databases. Multiple computational algorithms, including CIBERSORT, ESTIMATE, and xCell, were employed to assess the correlation between NT5E expression and immune cell infiltration. We found that NT5E was significantly overexpressed at both the mRNA and protein levels in LUAD tissues. Elevated NT5E expression was significantly linked to multiple clinicopathological factors, including metastasis and pathological stage, and served as a strong predictor of poor prognosis in LUAD patients. Gene Set Enrichment Analysis (GSEA) indicated that NT5E plays a crucial role in regulating immune responses, as evidenced by differential gene expression associated with NT5E levels. A strong positive correlation was observed between NT5E expression and the presence of immune cells, including dendritic cells, macrophages, and CD4 T cells, as well as the expression of various immune cell markers, suggesting that NT5E may influence the prognosis of LUAD patients by regulating immune cell infiltration. Additionally, drug sensitivity analysis highlights the potential of selumetinib and PD318088, both MEK1/2 inhibitors, to target NT5E in LUAD treatment, suggesting their use as single agents or in combination with other therapies. Collectively, these findings establish NT5E as a promising prognostic biomarker and therapeutic target in LUAD, particularly in the context of immune cell infiltration.
肺腺癌（LUAD）是肺癌最常见的类型，是癌症相关死亡的主要原因。NT5E是一种胞外5'-核苷酸酶，与癌症进展有关，尤其是在胞葬作用方面。尽管其可能参与其中，但NT5E在LUAD中的预后意义及其与免疫细胞浸润的关系尚未得到广泛研究。在本研究中，我们使用来自不同公共数据库的数据进行了全面分析，以阐明NT5E在LUAD中的表达模式及其预后意义。采用了多种计算算法，包括CIBERSORT、ESTIMATE和xCell，来评估NT5E表达与免疫细胞浸润之间的相关性。我们发现，NT5E在LUAD组织中的mRNA和蛋白质水平均显著过表达。NT5E表达升高与包括转移和病理分期在内的多个临床病理因素显著相关，并可作为LUAD患者预后不良的有力预测指标。基因集富集分析（GSEA）表明，NT5E在调节免疫反应中起关键作用，与NT5E水平相关的差异基因表达证明了这一点。观察到NT5E表达与包括树突状细胞、巨噬细胞和CD4 T细胞在内的免疫细胞的存在以及各种免疫细胞标志物的表达之间存在强正相关，这表明NT5E可能通过调节免疫细胞浸润来影响LUAD患者的预后。此外，药物敏感性分析突出了MEK1/2抑制剂司美替尼和PD318088在LUAD治疗中靶向NT5E的潜力，表明它们可作为单一药物或与其他疗法联合使用。总的来说，这些发现确立了NT5E作为LUAD中一个有前景的预后生物标志物和治疗靶点，特别是在免疫细胞浸润的背景下。
