PDF(Pubmed)
Abstract：
Gamma knife radiosurgery (GKRS) is recommended as the first-line treatment for brain metastases of lung adenocarcinoma (LUAD) in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 h after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.
摘要：
在许多指南中，伽玛刀放射外科（GKRS）被推荐作为肺腺癌脑转移（LUAD）的一线治疗方法。但其具体机制尚不清楚。我们旨在研究LUAD脑转移对GKRS超急性期的蛋白质组变化，并进一步探讨差异表达蛋白（DEPs）的机制。在手术切除大脑转移之前，从新辅助立体定向放射外科手术的临床试验中收集癌组织（ChiCTR2000038995）。GKRS后24h内收集5例LUAD脑转移组织。收集5例未行放疗的脑转移组织作为对照。蛋白质组学分析表明，163个蛋白质上调，25个蛋白质下调。GO和KEGG富集分析表明，DEP与核糖体密切相关。70个核糖体蛋白中有53个显著过表达，而他们都没有血压不足。由7种上调核糖体蛋白(RPL4、RPS19、RPS16、RPLP0、RPS2、RPS26和RPS25)构建的风险评分是LUAD患者生存时间的独立危险因素。核糖体蛋白的过表达可能代表对致死性放射治疗的绝望反应。我们提出靶向抑制这些核糖体蛋白可以增强GKRS的功效。
