Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, PR China.
Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, PR China.
J Pediatr Urol. 2022 Feb;18(1):14.e1-14.e8. doi: 10.1016/j.jpurol.2021.10.015. Epub 2021 Oct 26.
Although cure rate for Wilms tumor (WT) is high recent years, there is still small fraction of patients suffering from tumor relapse or metastases. It is urgent to identify more valuable biomarkers associated with disease progression. Previous studies have shown that PD-L1 was abnormally expressed in various type of cancers and acted as predictor for poor prognosis for those cancers. PD-1/PD-L1 inhibitors have achieved great success in various malignancies with correlation between PD-L1 expression and responses. We conducted this retrospective study to better understand the role of PD-L1 in WT development.
The aim of this study was to evaluate the expression rate of tumoral PD-L1 in WT and investigate the association of PD-L1 with tumor invasion and metastasis.
Seventy-seven patients with WT, including 20 cases of primary WTs with corresponding resected invasive/lymph node metastatic tumors were enrolled in the research. Immunohistochemistry was used to examine tumoral PD-L1 expression. Kaplan-Meier analysis with regard to the relationship between the expression of tumoral PD-L1 and follow-up information was performed.
Positive expression rate of tumoral PD-L1 was 28.6% in primary WT tissues, while 35% in associated invasive/metastatic ones. The tumoral PD-L1 expression in primary WTs were correlated with late stage and unfavorable histology (P = 0.007; P = 0.002). The expression rate of tumoral PD-L1 was higher in the progression group than that without distant metastasis or relapse (P = 0.038). The expression rate of PD-L1 between primary WTs and matched invasive/metastatic tissues was concordant (P = 0.435). Tumoral PD-L1 expression was associated with disease-free survival (DFS) and overall survival (OS) (P = 0.02; P = 0.03). Tumor PD-L1 expression was associated with DFS and OS in univariable analyses but not in multivariable Cox regression, adjusting for histology and tumor stage.
We found that PD-L1 expression was associated with the late-stage of WT and unfavorable histology, which were tightly associated with disease relapse and progression, predicting poor prognosis. The subsequent survival analysis also showed that PD-L1 expression was linked to both shorter DFS and OS. After adjustment for WT stage and histology, PD-L1 expression was no longer an independent predictor of DFS/OS. The value of PD-L1 as predictor for prognosis and potential therapeutic target in WT still need to be validated in large cohort in future.
Although PD-L1 expression correlated with established prognostic factors in our dataset, its value as a prognostic marker and therapeutic target, if any, remains to be shown in future.
尽管近年来肾母细胞瘤（WT）的治愈率很高，但仍有一小部分患者出现肿瘤复发或转移。因此，迫切需要识别更多与疾病进展相关的有价值的生物标志物。先前的研究表明，PD-L1 在多种类型的癌症中异常表达，并可作为这些癌症预后不良的预测因子。PD-1/PD-L1 抑制剂在与 PD-L1 表达相关的各种恶性肿瘤中取得了巨大成功。我们进行了这项回顾性研究，以更好地了解 PD-L1 在 WT 发展中的作用。
本研究旨在评估 WT 中肿瘤 PD-L1 的表达率，并探讨 PD-L1 与肿瘤侵袭和转移的关系。
本研究共纳入 77 例 WT 患者，包括 20 例原发性 WT 患者及其相应切除的侵袭性/淋巴结转移性肿瘤。采用免疫组织化学法检测肿瘤 PD-L1 表达。采用 Kaplan-Meier 分析 PD-L1 表达与随访信息的关系。
原发性 WT 组织中肿瘤 PD-L1 的阳性表达率为 28.6%，而相应的侵袭性/转移性肿瘤中为 35%。原发性 WT 中肿瘤 PD-L1 的表达与晚期和不良组织学有关（P=0.007；P=0.002）。进展组肿瘤 PD-L1 的表达率高于无远处转移或复发组（P=0.038）。原发性 WT 与匹配的侵袭性/转移性组织中 PD-L1 的表达率一致（P=0.435）。肿瘤 PD-L1 表达与无病生存期（DFS）和总生存期（OS）相关（P=0.02；P=0.03）。单变量分析显示，肿瘤 PD-L1 表达与 DFS 和 OS 相关，但多变量 Cox 回归分析调整组织学和肿瘤分期后，PD-L1 表达不再是 DFS/OS 的独立预测因子。
我们发现 PD-L1 表达与 WT 的晚期和不良组织学有关，这与疾病复发和进展密切相关，预示着预后不良。随后的生存分析也表明，PD-L1 表达与较短的 DFS 和 OS 相关。调整 WT 分期和组织学后，PD-L1 表达不再是 DFS/OS 的独立预测因子。PD-L1 作为预后标志物和潜在治疗靶点的价值仍需要在未来的大样本中进一步验证。
尽管 PD-L1 表达与我们数据集中的既定预后因素相关，但它作为预后标志物和治疗靶点的价值仍有待进一步证实。
