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SOX2 和 PRAME 在精原细胞瘤细胞的“重编程”中。

SOX2 and PRAME in the "reprogramming" of seminoma cells.

机构信息

Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy.

出版信息

Pathol Res Pract. 2022 Sep;237:154044. doi: 10.1016/j.prp.2022.154044. Epub 2022 Jul 28.

DOI:10.1016/j.prp.2022.154044

PMID:35930824

Abstract

BACKGROUND

In recent years, several studies investigated the complex process called "reprogramming" of seminoma (S) cells. The accepted pathogenetic model is a complex network including SOX2, SOX17, OCT3/4 and PRAME, which modulates the epigenetic transcription of numerous downstream genes and drives a divergent gene expression profile resulting in the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (M-GCTT), and finally to embryonal carcinoma (EC). Herein, we tested a large cohort of GCTT with SOX2 and PRAME to evaluate their expression in the evolutionary steps of GCTT and verify if the modulation in the expression of these two molecules could be relevant for the fate of GCTT.

METHODS

We tested 43, 19 and 17 consecutive and retrospectively enrolled cases of GCTT, germ cell neoplasia in situ (GCNIS) and uninvolved background testes (UBT), respectively. SOX2 and PRAME expressions have been evaluated with H-score and compared by adopting the appropriate statistic tests (Student's t-test and Mann-Whitney U test).

RESULTS

We found that SOX2 was more expressed by nonseminomatous-GCTT (NS-GCTT) (p < 0.001) and EC (p < 0.001) rather than S; by contrast, PRAME showed an opposite expression profile being expressed by S but not by NS-GCTT (p < 0.001) and EC (p < 0.001). S-C showed different expressions of SOX2 and PRAME compared to both P-S (p = 0.002 and <0.001, respectively) and EC (p < 0.001 and 0.042, respectively), with intermediate values between these latter two categories. GCNIS and UBT showed no expression of SOX2 (scattered positive Leydig cells) but high H-score levels of PRAME.

CONCLUSIONS

SOX2 and PRAME are differentially expressed and specularly modulated during the "reprogramming" of S cells [P-S (high levels of PRAME, no expression/low levels of SOX2) → S-C (intermediate levels of PRAME, intermediate levels of SOX2) → EC (no expression/low levels of PRAME, high levels of SOX2)], therefore supporting a complex pathogenetic model where the interactions between these two molecules are crucial in determining the fate of GCTT.

摘要

背景

近年来，已有多项研究探索了精原细胞瘤（S）细胞的复杂“重编程”过程。目前公认的发病机制模型是一个包含 SOX2、SOX17、OCT3/4 和 PRAME 的复杂网络，它调节许多下游基因的表观转录，并驱动不同的基因表达谱，从而导致从纯 S（P-S）向睾丸混合生殖细胞肿瘤（M-GCTT）的 S 成分（S-C），最终向胚胎癌（EC）的转变。在此，我们检测了大量 GCTT 的 SOX2 和 PRAME，以评估它们在 GCTT 进化步骤中的表达，并验证这两种分子表达的调节是否与 GCTT 的命运相关。

方法

我们分别测试了 43、19 和 17 例连续和回顾性纳入的 GCTT、生殖细胞肿瘤原位（GCNIS）和未受累背景睾丸（UBT）病例，采用 H 评分评估 SOX2 和 PRAME 的表达，并采用适当的统计学检验（Student's t 检验和 Mann-Whitney U 检验）进行比较。

结果

我们发现，非精原细胞瘤性-GCTT（NS-GCTT）（p<0.001）和 EC（p<0.001）中 SOX2 的表达高于 S；相反，PRAME 的表达呈相反模式，仅在 S 中表达，而在 NS-GCTT（p<0.001）和 EC（p<0.001）中不表达。S-C 的 SOX2 和 PRAME 表达与 P-S（p=0.002 和 <0.001）和 EC（p<0.001 和 0.042）相比存在差异，其值处于后两者之间。GCNIS 和 UBT 无 SOX2 表达（散在阳性 Leydig 细胞），但 PRAME 的 H 评分水平较高。

结论

SOX2 和 PRAME 在 S 细胞的“重编程”过程中呈现出差异表达和镜像调节[P-S（高 PRAME 水平，无表达/低 SOX2 水平）→S-C（中等 PRAME 水平，中等 SOX2 水平）→EC（无表达/低 PRAME 水平，高 SOX2 水平）]，因此支持一种复杂的发病机制模型，其中这两种分子的相互作用在决定 GCTT 的命运中至关重要。