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血浆外泌体 mRNA 可作为肝细胞癌微血管侵犯的预测标志物。

Exosomal mRNA in plasma serves as a predictive marker for microvascular invasion in hepatocellular carcinoma.

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

出版信息

J Gastroenterol Hepatol. 2024 Oct;39(10):2228-2238. doi: 10.1111/jgh.16677. Epub 2024 Jul 7.

Abstract

BACKGROUND AND AIM

There is a pressing need for non-invasive preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study investigates the potential of exosome-derived mRNA in plasma as a biomarker for diagnosing MVI.

METHODS

Patients with suspected HCC undergoing hepatectomy were prospectively recruited for preoperative peripheral blood collection. Exosomal RNA profiling was conducted using RNA sequencing in the discovery cohort, followed by differential expression analysis to identify candidate targets. We employed multiplexed droplet digital PCR technology to efficiently validate them in a larger sample size cohort.

RESULTS

A total of 131 HCC patients were ultimately enrolled, with 37 in the discovery cohort and 94 in the validation cohort. In the validation cohort, the expression levels of RSAD2, PRPSAP1, and HOXA2 were slightly elevated while CHMP4A showed a slight decrease in patients with MVI compared with those without MVI. These trends were consistent with the findings in the discovery cohort, although they did not reach statistical significance (P > 0.05). Notably, the expression level of exosomal PRPSAP1 in plasma was significantly higher in patients with more than 5 MVI than in those without MVI (0.147 vs 0.070, P = 0.035).

CONCLUSION

This study unveils the potential of exosome-derived PRPSAP1 in plasma as a promising indicator for predicting MVI status preoperatively.

摘要

背景与目的

肝细胞癌(HCC)患者术前准确预测微血管侵犯(MVI)至关重要。本研究旨在探讨外泌体来源的血浆 mRNA 作为 HCC 患者 MVI 术前诊断标志物的潜力。

方法

前瞻性纳入拟行肝切除术的 HCC 患者,术前采集外周血。采用 RNA 测序进行发现队列中外泌体 RNA 谱分析,采用差异表达分析筛选候选靶标。采用多重数字 PCR 技术对更大样本量的验证队列进行验证。

结果

共纳入 131 例 HCC 患者,其中发现队列 37 例,验证队列 94 例。在验证队列中,与无 MVI 患者相比,MVI 患者的 RSAD2、PRPSAP1 和 HOXA2 表达水平略有升高,CHMP4A 表达水平略有降低,但差异无统计学意义(P>0.05)。这些趋势与发现队列的结果一致,但均未达到统计学意义(P>0.05)。值得注意的是,血浆外泌体 PRPSAP1 的表达水平在 MVI 大于 5 个的患者中明显高于无 MVI 患者(0.147 比 0.070,P=0.035)。

结论

本研究揭示了血浆外泌体 PRPSAP1 作为预测 HCC 患者 MVI 术前状态的潜在标志物。

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