PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：这项研究调查了肾嫌色细胞癌（chRCC）和肾嗜酸细胞瘤（RO）的蛋白质组学景观，肾细胞癌的两种亚型合计约占所有肾肿瘤的10%。尽管它们的组织学相似性和共同起源，chRCC是一种需要积极干预的恶性肿瘤，而RO,良性增长，由于难以准确区分，通常会受到过度治疗。
方法：我们对chRCC（n=5）的实体活检进行了无标记的定量蛋白质组学分析，RO（n=5），和正常的邻近组织（NAT，n=5)。通过比较肿瘤和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确定了总共1610种蛋白质，对于一种肾组织类型(chRCC，RO,或NAT)。
结果：我们的发现揭示了关键代谢途径失调的显著相似性，包括碳水化合物,脂质，和氨基酸代谢，在chRCC和RO中。与NAT相比，chRCC和RO均显示糖异生蛋白明显下调，但是蛋白质的显着上调是柠檬酸盐循环的组成部分。有趣的是,我们观察到氧化磷酸化途径的明显分歧，RO显示蛋白质变化的数量和程度显着增加，超过chRCC中观察到的。
结论：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有价值的信息，并可能有助于开发改进的诊断和治疗策略。
方法：我们对chRCC（n=5）的实体活检进行了无标记的定量蛋白质组学分析，RO（n=5），和正常的邻近组织（NAT，n=5)。通过比较肿瘤和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确定了总共1610种蛋白质，对于一种肾组织类型(chRCC，RO,或NAT)。
结果：我们的发现揭示了关键代谢途径失调的显著相似性，包括碳水化合物,脂质，和氨基酸代谢，在chRCC和RO中。与NAT相比，chRCC和RO均显示糖异生蛋白明显下调，但是蛋白质的显着上调是柠檬酸盐循环的组成部分。有趣的是,我们观察到氧化磷酸化途径的明显分歧，RO显示蛋白质变化的数量和程度显着增加，超过chRCC中观察到的。
结论：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有价值的信息，并可能有助于开发改进的诊断和治疗策略。
