Testicular germ cell tumors (TGCTs) are ever more affecting the young male population. Germ cell neoplasia in situ (GCNIS) is the origin of TGCTs, namely, seminomas (SE) and a heterogeneous group of nonseminomas (NS) comprising embryonal carcinoma, teratoma, yolk sac tumor, and choriocarcinoma. Response to the treatment and prognosis, especially of NS, depend on precise diagnosis with a necessity for discovery of new biomarkers. We aimed to perform comprehensive in silico analysis at the DNA, RNA, and protein levels of six prospective (HOXA9, MGMT, CFC1, PRSS21, RASSF1A, and MAGEC2) and six known TGCT biomarkers (OCT4, SOX17, SOX2, SALL4, NANOG, and KIT) and assess its congruence with histopathological analysis in all forms of TGCTs. Cancer Hallmarks Analytics Tool, the Search Tool for the Retrieval of Interacting Genes/Proteins database, and UALCAN, an interactive web resource for analyzing cancer OMICS data, were used. In 108 TGCT and 48 tumor-free testicular samples, the immunoreactivity score (IRS) was calculated. SE showed higher frequency in DNA alteration, while DNA methylation was significantly higher for all prospective biomarkers in NS. In GCNIS, we assessed the clinical positivity of RASSF1 and PRSS21 in 52% and 62% of samples, respectively, in contrast to low or nil positivity in healthy seminiferous tubules, TGTCs as a group, SE, NS, or all NS components. Although present in approximately 80% of healthy seminiferous tubules (HT) and GCNIS, HOXA9 was diagnostically positive in 64% of TGCTs, while it was positive in 82% of NS versus 29% of SE. Results at the DNA, mRNA, and protein levels on putative and already known biomarkers were included in the suggested panels that may prove to be important for better diagnostics of various forms of TGCTs.

中文翻译：

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寻找 TGCT 生物标志物：全面的硅胶和组织病理学分析

睾丸生殖细胞肿瘤 (TGCT) 对年轻男性群体的影响越来越大。原位生殖细胞瘤(GCNIS) 是 TGCT 的起源，即精原细胞瘤 (SE) 和一组异质的非精原细胞瘤 (NS)，包括胚胎癌、畸胎瘤、卵黄囊瘤和绒毛膜癌。对治疗和预后的反应，尤其是 NS 的治疗和预后，取决于精确诊断以及发现新生物标志物的必要性。我们旨在对六种前瞻性（HOXA9、MGMT、CFC1、PRSS21、RASSF1A和MAGEC2）和六种已知的TGCT生物标志物（OCT4）的DNA、RNA和蛋白质水平进行全面的计算机分析。、SOX17、SOX2、SALL4、NANOG和KIT）并评估其与所有形式的 TGCT 的组织病理学分析的一致性。使用了癌症标志分析工具、用于检索相互作用基因/蛋白质数据库的搜索工具和用于分析癌症 OMICS 数据的交互式网络资源 UALCAN。在 108 份 TGCT 和 48 份无肿瘤睾丸样本中，计算了免疫反应性评分 (IRS)。SE 显示出更高的 DNA 改变频率，而 NS 中所有前瞻性生物标志物的 DNA 甲基化显着更高。在 GCNIS 中，我们评估了RASSF1和PRSS21的临床阳性分别在 52% 和 62% 的样本中阳性，而健康曲细精管、TGTC 作为一个组、SE、NS 或所有 NS 成分的阳性率低或为零。尽管HOXA9存在于大约 80% 的健康曲细精管 (HT) 和 GCNIS 中，但HOXA9在 64% 的TGCT 中呈诊断阳性，而在 82% 的 NS 和 29% 的 SE 中呈阳性。建议的面板中包括了假定的和已知的生物标志物的 DNA、mRNA 和蛋白质水平的结果，这些结果可能被证明对于更好地诊断各种形式的 TGCT 很重要。