Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital of Cologne, Cologne, Germany.
Department of Urology, Federal Armed Forces Hospital Koblenz, Koblenz, Germany.
Cancer. 2023 Feb 15;129(4):634-642. doi: 10.1002/cncr.34571. Epub 2022 Dec 11.
Before postchemotherapy retroperitoneal lymph node dissection (pcRPLND), in patients with metastasized germ cell tumors (GCTs), those harboring necrosis (NEC) cannot be distinguished from those who have teratoma (TER), resulting in relevant overtreatment, whereas microRNA-371a-3p may be predictive for viable GCT. The purpose of this study was to explore messenger RNA (mRNA) and proteins to distinguish TER from NEC in pcRPLND tissue.
The discovery cohort consisted in total of 48 patients, including 16 each with TER, viable GCT, and NEC. Representative areas were microdissected. A NanoString panel and proteomics were used to analyze 770 genes and >5000 proteins. The most significantly and differentially expressed combination of both parameters, mRNA and its associated protein, between TER and NEC was validated using immunohistochemistry (IHC) in an independent validation cohort comprising 66 patients who were not part of the discovery cohort.
The authors observed that anterior gradient protein 2 homolog (AGR2) and keratin, type I cytoskeletal 19 (KRT19) were significantly differentially expressed in TER versus NEC in mRNA and protein analyses (proteomics). The technical validation using IHC was successful in the same patients. These proteins were further validated by IHC in the independent patient cohort and exhibited significantly higher levels in TER versus NEC (p < .0001; area under the curve, 1.0; sensitivity and specificity, 100% each).
The current study demonstrated that KRT19 and AGR2 mRNA and protein are overexpressed in TER versus NEC in pcRPLND tissue and might serve as a future diagnostic target to detect TER, for instance, by functional imaging, to avoid overtreatment.
The proteins and the corresponding genes called AGR2 and KRT19 can differentiate between teratoma and necrosis in remaining tumor masses after chemotherapy in patients who have metastasized testicular cancer. This may be a way to improve presurgical diagnostics and to reduce the current overtreatment of patients with necrosis only, who could be treated sufficiently by surveillance.
在化疗后腹膜后淋巴结清扫术（pcRPLND）之前，转移性生殖细胞瘤（GCT）患者的坏死（NEC）与畸胎瘤（TER）无法区分，导致过度治疗，而 microRNA-371a-3p 可能可预测有活力的 GCT。本研究旨在探索信使 RNA（mRNA）和蛋白质以区分 pcRPLND 组织中的 TER 和 NEC。
发现队列共纳入 48 例患者，每组 16 例，分别为 TER、有活力的 GCT 和 NEC。代表性区域进行了显微解剖。使用 NanoString 面板和蛋白质组学分析了 770 个基因和 >5000 个蛋白质。在不包含在发现队列中的 66 例独立验证队列中，使用免疫组织化学（IHC）验证了 TER 和 NEC 之间 mRNA 及其相关蛋白之间差异最显著和表达差异最大的组合。
作者观察到，在 mRNA 和蛋白质分析（蛋白质组学）中，前梯度蛋白 2 同源物（AGR2）和角蛋白，I 型细胞骨架 19（KRT19）在 TER 与 NEC 之间差异表达显著。在相同患者中，使用 IHC 进行的技术验证成功。这些蛋白质在独立的患者队列中通过 IHC 进一步验证，并在 TER 中显示出与 NEC 相比显著更高的水平（p<0.0001；曲线下面积，1.0；灵敏度和特异性均为 100%）。
本研究表明，在 pcRPLND 组织中，KRT19 和 AGR2 mRNA 和蛋白在 TER 中表达高于 NEC，可能成为检测 TER 的未来诊断靶点，例如通过功能成像，以避免过度治疗。
