Characterization and proteomic analysis of plasma-derived small extracellular vesicles in locally advanced rectal cancer patients.

IF 6.6 2区 医学 Q1 Medicine
Cellular Oncology Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI:10.1007/s13402-024-00983-1
Haiyan Chen, Yimin Fang, Siqi Dai, Kai Jiang, Li Shen, Jian Zhao, Kanghua Huang, Xiaofeng Zhou, Kefeng Ding
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引用次数: 0

Abstract

Background: Neoadjuvant chemoradiotherapy (nCRT) stands as a pivotal therapeutic approach for locally advanced rectal cancer (LARC), yet the absence of a reliable biomarker to forecast its efficacy remains a challenge. Thus, this study aimed to assess whether the proteomic compositions of small extracellular vesicles (sEVs) might offer predictive insights into nCRT response among patients with LARC, while also delving into the proteomic alterations within sEVs post nCRT.

Methods: Plasma samples were obtained from LARC patients both pre- and post-nCRT. Plasma-derived sEVs were isolated utilizing the TIO2-based method, followed by LC-MS/MS-based proteomic analysis. Subsequently, pathway enrichment analysis was performed to the Differentially Expressed Proteins (DEPs). Additionally, ROC curves were generated to evaluate the predictive potential of sEV proteins in determining nCRT response. Public databases were interrogated to identify sEV protein-associated genes that are correlated with the response to nCRT in LARC.

Results: A total of 16 patients were enrolled. Among them, 8 patients achieved a pathological complete response (good responders, GR), while the remaining 8 did not achieve a complete response (poor responders, PR). Our analysis of pretreatment plasma-derived sEVs revealed 67 significantly up-regulated DEPs and 9 significantly down-regulated DEPs. Notably, PROC (AUC: 0.922), F7 (AUC: 0.953) and AZU1 (AUC: 0.906) demonstrated high AUC values and significant differences (P value < 0.05) in discriminating between GR and PR patients. Furthermore, a signature consisting of 5 sEV protein-associated genes (S100A6, ENO1, MIF, PRDX6 and MYL6) was capable of predicting the response to nCRT, yielding an AUC of 0.621(95% CI: 0.454-0.788). Besides, this 5-sEV protein-associated gene signature enabled stratification of patients into low- and high-risk group, with the low-risk group demonstrating a longer overall survival in the testing set (P = 0.048). Moreover, our investigation identified 11 significantly up-regulated DEPs and 31 significantly down-regulated DEPs when comparing pre- and post-nCRT proteomic profiles. GO analysis unveiled enrichment in the regulation of phospholipase A2 activity.

Conclusions: Differential expression of sEV proteins distinguishes between GR and PR patients and holds promise as predictive markers for nCRT response and prognosis in patients with LARC. Furthermore, our findings highlight substantial alterations in sEV protein composition following nCRT.

Abstract Image

局部晚期直肠癌患者血浆衍生小细胞外囊泡的特征和蛋白质组学分析
背景:新辅助化放疗(noadjuvant chemoradiotherapy,nCRT)是局部晚期直肠癌(local advanced rectal cancer,LARC)的关键治疗方法,但缺乏预测其疗效的可靠生物标志物仍是一项挑战。因此,本研究旨在评估小细胞外囊泡(sEVs)的蛋白质组组成是否能预测LARC患者的nCRT反应,同时深入研究nCRT后sEVs内的蛋白质组变化:方法:从 LARC 患者中获取 nCRT 前和 nCRT 后的血浆样本。利用基于 TIO2 的方法分离血浆中的 sEV,然后进行基于 LC-MS/MS 的蛋白质组学分析。随后,对差异表达蛋白(DEPs)进行了通路富集分析。此外,还生成了 ROC 曲线,以评估 sEV 蛋白在确定 nCRT 反应方面的预测潜力。对公共数据库进行了查询,以确定与 LARC nCRT 反应相关的 sEV 蛋白相关基因:结果:共有16名患者入组。结果:共有 16 名患者入选,其中 8 名患者获得了病理完全反应(良好反应者,GR),其余 8 名患者未获得完全反应(不良反应者,PR)。我们对治疗前血浆衍生的 sEVs 进行了分析,发现 67 个 DEPs 显著上调,9 个 DEPs 显著下调。值得注意的是,PROC(AUC:0.922)、F7(AUC:0.953)和 AZU1(AUC:0.906)显示出较高的 AUC 值和显著差异(P 值 结论):sEV 蛋白的差异表达可区分 GR 和 PR 患者,有望成为 LARC 患者 nCRT 反应和预后的预测标志物。此外,我们的研究结果还强调了 nCRT 后 sEV 蛋白组成的实质性改变。
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来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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