Razaghi Ali, Björnstedt Mikael
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
Cancers (Basel). 2024 Jun 28;16(13):2382. doi: 10.3390/cancers16132382.
Selenoprotein P (SELENOP) acts as a crucial mediator, distributing selenium from the liver to other tissues within the body. Despite its established role in selenium metabolism, the specific functions of SELENOP in the development of liver cancer remain enigmatic. This study aims to unravel SELENOP's associations in hepatocellular carcinoma (HCC) by scrutinizing its expression in correlation with disease characteristics and investigating links to hormonal and lipid/triglyceride metabolism biomarkers as well as its potential as a prognosticator for overall survival and predictor of hypoxia. SELENOP mRNA expression was analyzed in 372 HCC patients sourced from The Cancer Genome Atlas (TCGA), utilizing statistical methodologies in R programming and machine learning techniques in Python. SELENOP expression significantly varied across HCC grades ( < 0.000001) and among racial groups ( = 0.0246), with lower levels in higher grades and Asian individuals, respectively. Gender significantly influenced SELENOP expression ( < 0.000001), with females showing lower altered expression compared to males. Notably, the Spearman correlation revealed strong positive connections of SELENOP with hormonal markers (AR, ESR1, THRB) and key lipid/triglyceride metabolism markers (PPARA, APOC3, APOA5). Regarding prognosis, SELENOP showed a significant association with overall survival ( = 0.0142) but explained only a limited proportion of variability (~10%). Machine learning suggested its potential as a predictive biomarker for hypoxia, explaining approximately 18.89% of the variance in hypoxia scores. Future directions include validating SELENOP's prognostic and diagnostic value in serum for personalized HCC treatment. Large-scale prospective studies correlating serum SELENOP levels with patient outcomes are essential, along with integrating them with clinical parameters for enhanced prognostic accuracy and tailored therapeutic strategies.
硒蛋白P（SELENOP）作为一种关键介质，将肝脏中的硒分布到体内其他组织。尽管其在硒代谢中的作用已得到确立，但SELENOP在肝癌发生发展中的具体功能仍不清楚。本研究旨在通过仔细研究其与疾病特征相关的表达情况，以及调查其与激素和脂质/甘油三酯代谢生物标志物的联系，以及其作为总生存期预后指标和缺氧预测指标的潜力，来揭示SELENOP在肝细胞癌（HCC）中的关联。利用R编程中的统计方法和Python中的机器学习技术，对来自癌症基因组图谱（TCGA）的372例HCC患者的SELENOP mRNA表达进行了分析。SELENOP表达在不同HCC分级（<0.000001）和不同种族群体（=0.0246）中存在显著差异，在高分级和亚洲个体中水平较低。性别对SELENOP表达有显著影响（<0.000001），女性与男性相比表达变化较低。值得注意的是，Spearman相关性分析显示SELENOP与激素标志物（AR、ESR1、THRB）和关键脂质/甘油三酯代谢标志物（PPARA、APOC3、APOA5）之间存在强正相关。关于预后，SELENOP与总生存期存在显著关联（=0.0142），但仅解释了有限比例的变异性（约10%）。机器学习表明其有潜力作为缺氧的预测生物标志物，可以解释缺氧评分中约18.89%的方差。未来的方向包括验证SELENOP在血清中的预后和诊断价值，以实现HCC的个性化治疗。将血清SELENOP水平与患者预后相关的大规模前瞻性研究至关重要，同时将它们与临床参数相结合，以提高预后准确性和制定个性化治疗策略。
