Wang Rui, Zhang Weisong, Wu Jixiang, Chen Weiwei, Zhao Mengjie, Xu Yanhan, Li Xia, Song Jianxiang
Nantong University, Nantong, 226007, People's Republic of China.
Department of Thoracic Surgery, Yancheng Third People's Hospital, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People's Republic of China.
Sci Rep. 2025 Jan 6;15(1):925. doi: 10.1038/s41598-024-82129-9.
Estrogen sulfotransferase (SULT1E1), a member of the sulfotransferase family (SULTs), is the enzyme with the strongest affinity for estrogen. Despite significant associations between SULT1E1 and the progression and prognosis of a range of diseases, its functional role and potential mechanisms in lung adenocarcinoma (LUAD) remain unclear. The objective of this study was to examine the potential of SULT1E1 as a biomarker for LUAD. The molecular characteristics, disease relevance and expression levels of SULT1E1 in different cancers were analysed using public databases. GEPIA 2, Starbase and other databases were employed to analyse the expression levels of SULT1E1 in LUAD tissues and normal lung tissues, and to investigate the correlation with clinical stages. A prognostic analysis was conducted using the KM database and the tumour database. The SULT1E1 protein interaction network was constructed using the STRING database. The LUAD dataset from TCGA was employed for the purposes of performing functional enrichment and immune infiltration analyses. Subsequently, the expression levels of SULT1E1 in LUAD cell lines, human LUAD tissues and normal tissues were detected by Western blot and other methods. The expression of SULT1E1 was further detected by immunohistochemical staining, and the correlation between the expression level of SULT1E1 and the clinical characteristics and prognosis of LUAD patients was verified. The expression of SULT1E1 in cytoplasm and nucleus was detected by cellular immunofluorescence. Significant reductions in SULT1E1 expression were observed across various tissues and cell lines of LUAD, as supported by both bioinformatics and Western blotting analyses. Analysis of gene ontology suggested that SULT1E1 potentially exerts anticarcinogenic effects by modulating protein serine/threonine kinase activity and its associated pathway. Additionally, KEGG and GSEA analyses indicated SULT1E1's involvement in drug metabolism, choline metabolism in cancer, hormone synthesis, and other relevant pathways. Examination of immune infiltration demonstrated a strong correlation between SULT1E1 expression and the presence of immune cells such as TAM and Treg. Furthermore, SULT1E1 expression levels in LUAD were found to correlate with TNM stage, histological stage, platelet count to lymphocyte count ratio (PLR), neutrophil count to lymphocyte count ratio (NLR), and systemic immune-inflammation index (SII). Low SULT1E1 expression levels were significantly associated with shorter overall survival (OS) in LUAD patients. The suppression of lung adenocarcinoma (LUAD) by SULT1E1 makes it a potential biomarker for diagnosing and predicting the prognosis of LUAD.
雌激素磺基转移酶（SULT1E1）是磺基转移酶家族（SULTs）的成员之一，是对雌激素亲和力最强的酶。尽管SULT1E1与一系列疾病的进展和预后之间存在显著关联，但其在肺腺癌（LUAD）中的功能作用和潜在机制仍不清楚。本研究的目的是探讨SULT1E1作为LUAD生物标志物的潜力。利用公共数据库分析了SULT1E1在不同癌症中的分子特征、疾病相关性和表达水平。使用GEPIA 2、Starbase等数据库分析SULT1E1在LUAD组织和正常肺组织中的表达水平，并研究其与临床分期的相关性。使用KM数据库和肿瘤数据库进行预后分析。使用STRING数据库构建SULT1E1蛋白相互作用网络。利用TCGA的LUAD数据集进行功能富集和免疫浸润分析。随后，通过蛋白质印迹法和其他方法检测SULT1E1在LUAD细胞系、人LUAD组织和正常组织中的表达水平。通过免疫组织化学染色进一步检测SULT1E1的表达，并验证SULT1E1表达水平与LUAD患者临床特征和预后的相关性。通过细胞免疫荧光检测SULT1E1在细胞质和细胞核中的表达。生物信息学和蛋白质印迹分析均支持在LUAD的各种组织和细胞系中观察到SULT1E1表达显著降低。基因本体分析表明，SULT1E1可能通过调节蛋白丝氨酸/苏氨酸激酶活性及其相关途径发挥抗癌作用。此外，KEGG和GSEA分析表明SULT1E1参与药物代谢、癌症中的胆碱代谢、激素合成及其他相关途径。免疫浸润检查表明SULT1E1表达与TAM和Treg等免疫细胞的存在密切相关。此外，发现LUAD中SULT1E1表达水平与TNM分期、组织学分期、血小板计数与淋巴细胞计数比值（PLR）、中性粒细胞计数与淋巴细胞计数比值（NLR）及全身免疫炎症指数（SII）相关。LUAD患者中低SULT1E1表达水平与较短的总生存期（OS）显著相关。SULT1E1对肺腺癌（LUAD）的抑制作用使其成为诊断和预测LUAD预后的潜在生物标志物。
