Department of Urology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan.
Bioscience Division, Research and Development Department, Tosoh Corporation, Ayase, Kanagawa, Japan.
Sci Rep. 2024 Nov 19;14(1):28639. doi: 10.1038/s41598-024-80248-x.
Renal and ovarian clear cell carcinoma (CCC) are both characterized by a clear cytoplasm and exhibit similar genomic alterations and clinical characteristics. We hypothesized that both CCCs may share clinical biomarker. Tissue factor pathway inhibitor 2 (TFPI2), a serine protease inhibitor, has emerged as a promising serum biomarker for ovarian CCC, and we evaluated the efficacy of TFPI2 as a biomarker for renal cell carcinoma (RCC). Serum samples were collected from patients with RCC and healthy volunteers, and TFPI2 levels were measured. Expression of TFPI2 in each cell type was evaluated using single-cell RNA sequencing. Survival analyses according to TFPI2 expression levels were performed based on publicly available databases. Serum TFPI2 was significantly elevated in patients with RCC compared to healthy volunteers, particularly those with clear cell histology. Metastatic RCC tumors exhibited higher TFPI2 than localized RCCs. Moreover, higher TFPI2 correlated with higher Fuhrman grades in clear cell RCC. Publicly available databases showed an association between TFPI2 expression and overall survival, particularly in clear cell RCC. Single-cell RNA sequencing confirmed TFPI2 expression in clear cell RCC and normal kidney tubular epithelial cells. TFPI2 has emerged as a potential serum biomarker for RCC, offering avenues for improved detection and prognostication.
肾透明细胞癌和卵巢透明细胞癌均具有透明细胞质特征，表现出相似的基因组改变和临床特征。我们假设这两种 CCC 可能具有共同的临床生物标志物。组织因子途径抑制剂 2（TFPI2）是一种丝氨酸蛋白酶抑制剂，已成为卵巢透明细胞癌有前途的血清生物标志物，我们评估了 TFPI2 作为肾细胞癌（RCC）标志物的功效。收集了 RCC 患者和健康志愿者的血清样本，并测量了 TFPI2 水平。使用单细胞 RNA 测序评估了每个细胞类型中 TFPI2 的表达。根据公开可用的数据库进行了根据 TFPI2 表达水平的生存分析。与健康志愿者相比，RCC 患者的血清 TFPI2 水平显着升高，尤其是具有透明细胞组织学的患者。转移性 RCC 肿瘤的 TFPI2 水平高于局限性 RCC。此外，TFPI2 水平与透明细胞 RCC 的 Fuhrman 分级较高相关。公开可用的数据库显示 TFPI2 表达与总生存率之间存在关联，尤其是在透明细胞 RCC 中。单细胞 RNA 测序证实了 TFPI2 在透明细胞 RCC 和正常肾脏管状上皮细胞中的表达。TFPI2 已成为 RCC 的潜在血清生物标志物，为提高检测和预后提供了途径。
