Drendel Vanessa, Heckelmann Bianca, Schell Christoph, Kook Lucas, Biniossek Martin L, Werner Martin, Jilg Cordula A, Schilling Oliver
1Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
2Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Stefan Meier Strasse 17, 79104 Freiburg, Germany.
Clin Proteomics. 2018 Aug 3;15:25. doi: 10.1186/s12014-018-9200-6. eCollection 2018.
Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5-7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.
We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.
At 1% false discovery rate, we identified > 3900 proteins, of which > 2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.
We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.
肾嗜酸细胞瘤（RO）是肾脏的良性上皮性肿瘤，而嫌色肾细胞癌（chRCC）是恶性肾肿瘤。后者占肾肿瘤的5 - 7%。RO和chRCC在分子和组织学上表现出明显的相似性，这使得它们的鉴别具有挑战性。我们旨在对RO和早期chRCC进行差异蛋白质组分析，以便更好地了解区分性的蛋白质模式。
我们使用福尔马林固定、石蜡包埋的样本（6例RO病例，6例chRCC病例）以及同位素三重二甲基化和一个混合参考标准，以实现全队列的定量比较。对于溶酶体相关膜蛋白1（LAMP1）和整合素α-V（ITGAV），我们在42例RO病例和31例chRCC病例的扩展队列中进行了验证性免疫组织化学（IHC）。
在1%的错误发现率下，我们鉴定出>3900种蛋白质，其中>2400种蛋白质在至少4例RO和4例chRCC病例中得到一致定量。蛋白质组表达谱区分了RO和chRCC，并突出了已确定的特征，如RO中线粒体蛋白的积累，同时强调了chRCC中内溶酶体蛋白的积累。与蛋白质组数据一致，IHC显示chRCC中LAMP1富集，RO中ITGAV富集。
我们展示了首批关于RO和chRCC的差异蛋白质组分析研究之一，并突出了这些肾肿瘤中LAMP1和ITGAV的差异丰度。
