Sundqvist Benjamin, Kilpinen Sami, Böhling Tom, Koljonen Virve, Sihto Harri
Department of Pathology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.
Molecular and Integrative Biosciences Research Programme, University of Helsinki, 00014 Helsinki, Finland.
Cancers (Basel). 2022 Jul 23;14(15):3591. doi: 10.3390/cancers14153591.
Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin with a poor prognosis. Improving the prognosis of MCC by means of targeted therapies requires further understanding of the mechanisms that drive tumor progression. In this study, we aimed to identify the genes, processes, and pathways that play the most crucial roles in determining MCC outcomes.
We investigated transcriptomes generated by RNA sequencing of formalin-fixed paraffin-embedded tissue samples of 102 MCC patients and identified the genes that were upregulated among survivors and in patients who died from MCC. We subsequently cross-referenced these genes with online databases to investigate the functions and pathways they represent. We further investigated differential gene expression based on viral status in patients who died from MCC.
We found several novel genes associated with MCC-specific survival. Genes upregulated in patients who died from MCC were most notably associated with angiogenesis and the PI3K-Akt and MAPK pathways; their expression predominantly had no association with viral status in patients who died from MCC. Genes upregulated among survivors were largely associated with antigen presentation and immune response.
This outcome-based discrepancy in gene expression suggests that these pathways and processes likely play crucial roles in determining MCC outcomes.
默克尔细胞癌（MCC）是一种罕见但侵袭性很强的皮肤神经内分泌癌，预后较差。通过靶向治疗改善MCC的预后需要进一步了解驱动肿瘤进展的机制。在本研究中，我们旨在确定在决定MCC预后方面发挥最关键作用的基因、过程和通路。
我们研究了102例MCC患者福尔马林固定石蜡包埋组织样本的RNA测序产生的转录组，并确定了在幸存者和死于MCC的患者中上调的基因。随后，我们将这些基因与在线数据库进行交叉引用，以研究它们所代表的功能和通路。我们还根据死于MCC患者的病毒状态进一步研究了差异基因表达。
我们发现了几个与MCC特异性生存相关的新基因。在死于MCC的患者中上调的基因最显著地与血管生成以及PI3K-Akt和MAPK通路相关；它们的表达在死于MCC的患者中主要与病毒状态无关。在幸存者中上调的基因主要与抗原呈递和免疫反应相关。
这种基于结果的基因表达差异表明，这些通路和过程可能在决定MCC预后方面发挥关键作用。
