Gene expression microarray analysis of adult testicular germ cell tumor: a comparison between pure-type seminomas and seminoma components in mixed tumors

Gene expression microarray analysis of adult testicular germ cell tumor: a comparison between pure-type seminomas and seminoma components in mixed tumors
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成人睾丸生殖细胞肿瘤的基因表达微阵列分析:纯型精原细胞瘤与混合肿瘤中精原细胞瘤成分的比较

DOI:
10.1007/s00428-021-03168-5
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发表时间:
2021
期刊:
影响因子:
3.5
通讯作者:
Tsuda Hitoshi
Tsuda Hitoshi
中科院分区:
医学3区
文献类型:
--
作者:
Miyai Kosuke;Yonekura Yuiko;Ito Keiichi;Matsukuma Susumu;Tsuda Hitoshi

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我们先前证明了混合性睾丸生殖细胞肿瘤(TGCT)从睾丸间质细胞瘤进展为胚胎性癌的遗传学证据。这一过程,即肿瘤细胞的“重编程”,对于病理性肿瘤发生至关重要,在设计临床治疗策略时应牢记在心。我们假设纯型腺瘤和混合型腺瘤(混合型腺瘤)中腺瘤成分之间的比较可以揭示重编程过程的早期变化。在本研究中,我们进行了基因表达微阵列分析的六个纯型和六个混合型腺瘤。分层聚类分析正确地将每种类型的腺瘤分为一个单独的集群。纯型和混合型腺瘤之间的监督分析揭示了154个显著失调的基因(Storey校正q < 0.05)。与纯型乳腺癌相比,混合型乳腺癌中过表达最高的基因包括MT 1亚型、PRSS 8、TSC 22 D1和SLC 39 A4;下调基因包括DEFB 123、LMTK 2和MYRF。差异表达基因的功能注释分析显示,功能类别最高的是与细胞锌代谢相关的MT 1亚型和SLC 39 A4,其结果通过定量聚合酶链反应和免疫组织化学分析得到验证。总之,这项研究提供了进一步的证据表明,纯型和混合型胶质瘤在分子上是不同的,这可能有助于阐明TGCT进展中的重编程机制。
We previously demonstrated a genetic evidence of the progression from seminoma to embryonal carcinoma in mixed testicular germ cell tumors (TGCTs). This process, the “reprogramming” of seminoma cells, is crucial for pathological tumorigenesis and should be kept in mind while designing clinical therapeutic strategies. We hypothesized that a comparison between pure-type seminomas and seminoma components in mixed tumors (mixed-type seminomas) could reveal early changes in the reprogramming process. In the present study, we performed gene expression microarray analysis of six pure-type and six mixed-type seminomas. Hierarchical clustering analysis properly grouped each type of seminomas into a separated cluster. Supervised analysis between pure-type and mixed-type seminomas revealed 154 significantly dysregulated genes (Storey-adjustedq< 0.05). The genes with the highest overexpression in mixed-type seminomas compared with the pure-type seminomas includedMT1isoforms,PRSS8,TSC22D1, andSLC39A4; downregulated genes includedDEFB123,LMTK2, andMYRF. Functional annotation analysis of the differentially expressed genes revealed that the top-ranked functional categories were related to cellular zinc metabolism and consisted ofMT1isoforms andSLC39A4, the results of which were validated using quantitative polymerase chain reaction and immunohistochemical analysis. In conclusion, this research provides further evidence that pure and mixed types of seminomas are molecularly different, which may contribute to elucidate the reprogramming mechanism in the progression of TGCTs.
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