Carvalho Luis B, Jorge Susana, López-Fernández Hugo, Lodeiro Carlos, Dhir Rajiv, Campos Pinheiro Luis, Medeiros Mariana, Santos Hugo M, Capelo José L
BIOSCOPE Research Group, LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, FCT NOVA, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal.
PROTEOMASS Scientific Society, Departamental Building, FCT-NOVA, Caparica Campus, 2829-516, Caparica, Portugal.
Clin Proteomics. 2023 Nov 28;20(1):54. doi: 10.1186/s12014-023-09443-8.
This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation.
We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT).
Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC.
This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.
本研究调查了嫌色性肾细胞癌（chRCC）和肾嗜酸细胞瘤（RO）的蛋白质组图谱，这两种肾细胞癌亚型合计约占所有肾肿瘤的10%。尽管它们在组织学上有相似之处且起源相同，但chRCC是一种需要积极干预的恶性肿瘤，而RO作为良性生长，由于难以准确鉴别，常面临过度治疗。
我们对chRCC（n = 5）、RO（n = 5）及正常相邻组织（NAT，n = 5）的实体活检组织进行了无标记定量蛋白质组分析。通过比较肿瘤标本与NAT标本之间的蛋白质丰度进行定量分析。我们的分析在所有样本中共鉴定出1610种蛋白质，其中1379种（85.7%）蛋白质在一种肾组织类型（chRCC、RO或NAT）的十次液相色谱-串联质谱（LC-MS/MS）运行中至少有七次被定量。
我们的研究结果显示，chRCC和RO在关键代谢途径的失调方面存在显著相似性，包括碳水化合物、脂质和氨基酸代谢。与NAT相比，chRCC和RO的糖异生蛋白均显著下调，但柠檬酸循环相关蛋白则显著上调。有趣的是，我们在氧化磷酸化途径中观察到明显差异，RO中蛋白质改变的数量和程度显著增加，超过了chRCC中的变化。
本研究强调了整合高分辨率质谱蛋白质定量分析以有效表征和区分诊断为chRCC和RO的实体肿瘤活检组织蛋白质组图谱的价值。本研究获得的见解为增进我们对这些疾病的理解提供了有价值的信息，并可能有助于开发改进的诊断和治疗策略。
