Abstract：
17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.
摘要：
17-β-雌二醇，参与间皮瘤的发病机制，并将其前体作为潜在的生物标志物用于间皮瘤的早期诊断。使用酶联免疫吸附测定（ELISA）对17-β-雌二醇和超高效液相色谱/串联质谱（UHPLC-MS/MS）对19种17-β-雌二醇前体，对间皮瘤患者血清中的20种类固醇激素进行了综合分析（n=67），接触石棉的健康受试者(n=39)，和非石棉暴露的健康受试者（n=35）。生物信息学分析探索了三种潜在的血清生物标志物：17-β-雌二醇，DHEA-S,和雄烯二酮.结果表明，间皮瘤患者与非石棉暴露和石棉暴露的健康受试者之间的17-β-雌二醇水平存在显着差异。在不同分期的间皮瘤患者中,血清17-β-雌二醇水平无明显变化,提示其作为早期诊断标志物的潜力。17-β-雌二醇水平在环境和职业性石棉接触的间皮瘤患者中相似，与女性相比，职业性石棉暴露的男性表现出明显更高的17-β-雌二醇水平。与未接触石棉的个体相比，在接触石棉的个体中观察到雄烯二酮的显着减少和DHEA-S的增加。对DHEA-S-雄烯二酮-17-β-雌二醇签名评分的分析显示，与非接触石棉的个体相比，接触石棉的个体和间皮瘤患者增加，这个分数有效地区分了各组。癌症基因组图谱数据用于分析5-α-还原酶1和羟基类固醇-17β-脱氢酶2基因的表达。研究结果表明，5-α-还原酶1和羟基类固醇-17β-脱氢酶2基因值升高的间皮瘤患者的总体生存预后较差或较好。分别。总之,这项研究表明17-β-雌二醇，DHEA-S,和雄烯二酮作为间皮瘤风险的生物标志物，并在接触石棉的个体中早期诊断间皮瘤，协助及时干预和改善护理。
