Jędroszka Dorota, Orzechowska Magdalena, Bednarek Andrzej K
Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.
Arch Med Sci. 2017 Oct;13(6):1249-1254. doi: 10.5114/aoms.2017.65649. Epub 2017 Jan 31.
Notch signalling, an evolutionarily conserved mechanism of cellular differentiation and tissue remodelling, is frequently deregulated in several human malignancies, including renal cell carcinoma (RCC). However, the prognostic value of individual Notch pathway members in RC subtypes remains indefinable. The present study investigates whether the differential expression of Notch members has a contrary effect on disease-free survival (DFS) in clear cell renal cell carcinoma (KIRC), papillary cell renal cell carcinoma (KIRP) and chromophobe renal cell carcinoma (KICH) patients.
The predictive value of 19 Notch members was evaluated in KICH, KIRC and KIRP patient cohorts from The Cancer Genome Atlas (TCGA). Results in the form of Kaplan-Meier survival plots with the -value calculated (log-rank test, < 0.05) enabled the patients to be split into favourable/unfavourable prognosis groups regarding expression of Notch members.
More specifically, lowered expression of ADAM17 correlated with good prognosis in KICH, KIRC and KIRP (HR = 7.79, = 0.03; HR = 3.98, = 0.051; HR = 11.24, < 0.001, respectively). Additionally, HES4 differentiated KICH and KIRC, as its higher expression correlated with good prognosis in KICH and favourable lowered expression in KIRC (HR = 0.11, = 0.015; HR = 2.42, < 0.001, respectively).
Our analysis could be valuable for better understanding of the molecular mechanism of renal carcinoma. The expression of Notch pathway members could be a useful biomarker for predicting favourable/unfavourable prognosis in patients with RCC.
Notch信号通路是一种在细胞分化和组织重塑过程中进化保守的机制,在包括肾细胞癌(RCC)在内的多种人类恶性肿瘤中经常失调。然而,Notch通路单个成员在RCC亚型中的预后价值仍不明确。本研究调查了Notch成员的差异表达是否对透明细胞肾细胞癌(KIRC)、乳头状肾细胞癌(KIRP)和嫌色肾细胞癌(KICH)患者的无病生存期(DFS)产生相反影响。
在来自癌症基因组图谱(TCGA)的KICH、KIRC和KIRP患者队列中评估了19个Notch成员的预测价值。以Kaplan-Meier生存曲线形式呈现的结果以及计算出的P值(对数秩检验,P<0.05)能够根据Notch成员的表达情况将患者分为预后良好/不良组。
更具体地说,ADAM17表达降低与KICH、KIRC和KIRP的良好预后相关(HR分别为7.79,P = 0.03;HR = 3.98,P = 0.051;HR = 11.24,P<0.001)。此外,HES4可区分KICH和KIRC,因为其高表达与KICH的良好预后相关,而在KIRC中表达降低则预后良好(HR分别为0.11,P = 0.015;HR = 2.42,P<0.001)。
我们的分析对于更好地理解肾癌的分子机制可能具有重要价值。Notch通路成员的表达可能是预测RCC患者预后良好/不良的有用生物标志物。