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.

中文翻译：

---

嫌色肾细胞癌和良性肾嗜酸细胞瘤活检的蛋白质组学分析揭示了共同的代谢失调

本研究调查了嫌色肾细胞癌 (chRCC) 和肾嗜酸细胞瘤 (RO) 的蛋白质组学景观，这两种肾细胞癌亚型合计约占所有肾肿瘤的 10%。尽管它们的组织学相似且起源相同，但 chRCC 是一种恶性肿瘤，需要积极干预，而 RO 是一种良性生长，由于难以准确区分，常常受到过度治疗。我们对 chRCC (n = 5)、RO (n = 5) 和正常邻近组织 (NAT，n = 5) 的固体活检进行了无标记定量蛋白质组分析。通过比较肿瘤和 NAT 样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总共鉴定出了 1610 种蛋白质，其中 1379 种蛋白质 (85.7%) 在针对一种肾组织类型（chRCC、RO 或 NAT）的 10 次 LC-MS/MS 运行中至少有 7 次进行了定量。我们的研究结果揭示了 chRCC 和 RO 中关键代谢途径（包括碳水化合物、脂质和氨基酸代谢）失调的显着相似性。与 NAT 相比，chRCC 和 RO 的糖异生蛋白均显着下调，但柠檬酸循环中不可或缺的蛋白显着上调。有趣的是，我们观察到氧化磷酸化途径存在明显差异，RO 显示蛋白质改变的数量和程度显着增加，超过了 chRCC 中观察到的情况。这项研究强调了整合高分辨率质谱蛋白质定量以有效表征和区分诊断为 chRCC 和 RO 的实体瘤活检的蛋白质组景观的价值。从这项研究中获得的见解为增强我们对这些疾病的理解提供了宝贵的信息，并可能有助于制定改进的诊断和治疗策略。