Department of Urology, Medical School, University of Pecs, Pecs, Hungary.
Institute of Biochemistry, University of Muenster, Muenster, Germany.
Cell Oncol (Dordr). 2022 Feb;45(1):193-198. doi: 10.1007/s13402-021-00650-9. Epub 2021 Dec 11.
Approximately 15% of clinically localised conventional renal cell carcinomas (cRCC) develop metastases within 5 years of follow-up. Sarcomatous cRCC is a highly malignant cancer of the kidney. The aim of our study was to identify biomarkers for estimating the postoperative progression of cRCCs.
Global microarray-based gene expression analysis of RCCs with and without sarcomatous changes revealed that a high MMP12 expression was associated with a sarcomatous histology. Additionally, we analysed MMP12 expression using a multi-tissue array comprising 736 cRCC patients without metastasis at the time of surgery. The median follow-up time was 66 ± 29 months.
Immunohistochemistry revealed MMP12 expression in 187 of 736 cRCCs with good follow-up data. Subsequent Kaplan-Meier analysis revealed that patients with MMP12 positive tumours exhibited a significantly shorter tumour-free survival (p < 0.001). In multivariate Cox regression analysis a weak to strong MMP12 expression indicated a 2.4-2.8 times higher risk of postoperative tumour relapse (p < 0.001; p < 0.003, respectively).
MMP12 may serve as a biomarker to estimate postoperative cRCC relapse and as a possible target for penfluridol therapy.
大约 15%的临床局限性传统肾细胞癌(cRCC)在随访 5 年内会发展为转移。肉瘤样 cRCC 是一种高度恶性的肾癌。我们研究的目的是确定用于估计 cRCC 术后进展的生物标志物。
对伴有和不伴有肉瘤样改变的 RCC 进行基于全基因组的基因表达分析,结果显示 MMP12 高表达与肉瘤样组织学相关。此外,我们使用包含 736 例手术时无转移的 cRCC 患者的多组织阵列分析 MMP12 的表达。中位随访时间为 66±29 个月。
免疫组化显示 736 例 cRCC 中有 187 例有良好的随访数据存在 MMP12 表达。随后的 Kaplan-Meier 分析显示 MMP12 阳性肿瘤患者的无肿瘤生存期明显缩短(p<0.001)。在多变量 Cox 回归分析中,弱至强 MMP12 表达表明术后肿瘤复发的风险增加 2.4-2.8 倍(p<0.001;p<0.003)。
MMP12 可作为估计术后 cRCC 复发的生物标志物,也可能成为 penfluridol 治疗的潜在靶点。