鉴别STAT5B作为子宫内膜癌早期诊断的生物标志物

Pub Date : 2023-01-01 DOI:10.32604/biocell.2023.030086
XUELIAN CHEN, YUNZHENG ZHANG, JUNJIAN HE, YIBING LI
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引用次数: 0

摘要

背景:晚期子宫内膜癌(EC)的晚期发现往往导致患者预后不良。因此,确定可靠的生物标志物以促进早期发现EC非常重要。信号换能器和转录激活器(STAT)家族成员在几种肿瘤中发挥重要作用,然而,它们对EC发生和进展的影响尚不清楚。方法:采用机器学习方法探讨STAT5B在EC中的重要性。结果:因此,我们通过UALCAN数据挖掘平台发现,在EC中STAT1和STAT2上调,STAT5A、STAT5B和STAT6下调。STAT5B和STAT6的高表达预示着良好的临床结果,而STAT1和STAT2的高表达预示着不良的临床结果。随后的通路富集分析显示STAT家族主要参与凋亡通路激活、细胞周期破坏和上皮-间质转化。药敏分析显示STAT5A/5B表达与EC耐药呈负相关。此外,STAT5B mRNA和蛋白的表达与多种临床病理特征相关。肿瘤免疫估计资源(Tumor Immune estimate Resource, TIMER)分析显示,STAT5B的表达与浸润的CD8+ T细胞和中性粒细胞的丰度呈正相关,而其拷贝数的变化与整体免疫细胞浸润相关。在cBio Cancer Portal中,STAT5B与子宫内膜癌(UCEC)中STAT5B表达与相关基因的相关性数据显示,STAT5B与KIAA0753(又称moonraker、OFIP)表达相关性最密切,其次是COL27A1在EC中的表达。通路富集分析进一步表明stat5b相关基因参与了丝裂原活化蛋白激酶(MAPK)和Ras信号通路。结论:总的来说,我们的发现为STAT家族在EC中的作用提供了新的见解。它还强调了未来诊断和预后标记物研究的新靶点,以及STAT5B作为药物敏感性筛选的新标记物。
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Identification of STAT5B as a biomarker for an early diagnosis of endometrial carcinoma
Background: The late detection of endometrial carcinoma (EC) at an advanced stage often results in a poor patient prognosis. It is hence important to identify reliable biomarkers to facilitate early detection of EC. Signal transducer and activator of transcription (STAT) family members play an important role in several tumors, however, their impact on EC development and progression remains unclear. Methods: Machine learning methods were used to investigate the importance of STAT5B in EC. Results: Hence, we explored the UALCAN data mining platform and found that while STAT1 and STAT2 were upregulated, STAT5A, STAT5B, and STAT6 were downregulated in EC. This high expression of STAT5B and STAT6 predicted favorable clinical outcomes, whereas the increased expression of STAT1 and STAT2 predicted poor clinical outcomes. Subsequent pathway enrichment analysis revealed that the STAT family was mainly involved in apoptosis pathway activation, cell cycle disruption, and epithelial–mesenchymal transition. Drug sensitivity analysis demonstrated that STAT5A/5B expression was negatively correlated with drug resistance in EC. Further, the expression of STAT5B mRNA and protein was correlated with several clinicopathological characteristics. Tumor Immune Estimation Resource (TIMER) analysis revealed that STAT5B expression was positively correlated with the abundance of infiltrating CD8+ T cells and neutrophils while its copy number variation was associated with the overall immune cell infiltration. The data on the correlations between STAT5B expression and related genes in uterine corpus endometrial carcinoma (UCEC) in cBio Cancer Portal showed the closest correlation of STAT5B expression with that of KIAA0753 (also known as moonraker and OFIP), followed by COL27A1 in EC. Pathway enrichment analysis further showed that STAT5B-related genes were involved in the mitogen-activated protein kinase (MAPK) and Ras signaling pathways. Conclusion: Collectively, our findings provided new insights into the role of the STAT family in EC. It also highlighted new targets for future research on diagnostic and prognostic markers and STAT5B as a novel marker for drug sensitivity screening.
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