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液体活检(血液 cfRNA)中 RRM1 基因表达作为放疗诱导口腔黏膜炎的非侵入性预测因子和头颈部癌症患者潜在的预后生物标志物的评估。

RRM1 gene expression evaluated in the liquid biopsy (blood cfRNA) as a non-invasive, predictive factor for radiotherapy-induced oral mucositis and potential prognostic biomarker in head and neck cancer patients.

机构信息

Department of Human Physiology, Medical University of Lublin, Lublin, Poland.

Department of Oncology, Medical University of Lublin, Lublin, Poland.

出版信息

Cancer Biomark. 2018;22(4):657-667. doi: 10.3233/CBM-171082.

Abstract

BACKGROUND

Intensified treatment of head and neck cancers (HNC): by radiotherapy (RTH) commonly combined with cytotoxic drugs is associated with oral mucositis (OM). Changes in the functioning of nucleotide synthesis pathway (RNR1, coded by RRM1 gene) can modulate the efficiency of cellular DNA repair mechanisms and influence the risk of occurrence and severity of OM in HNC patients after RTH.

OBJECTIVE

The objective of this study was to evaluate the correlation between expression of RRM1 gene measured in free circulating RNA (cfRNA) and the risk of more severe OM and disease-free survival (DFS) and overall survival (OS) in patients undergoing RTH for HNC.

METHODS

The study included 60 patients treated with RTH for HNC. RRM1 gene expression was examined in circulating RNA isolated from peripheral blood plasma (before treatment).

RESULTS

High RRM1 gene expression was significantly associated with higher risk of grade 3 OM after 5 (OR = 4.97), 6 (OR = 4.33) and 7 (OR = 3.50) weeks of RTH. Expression of RRM1 gene was not significantly related with risk of DFS and OS shortening (however well separated Kaplan-Meier curves might suggest its potential prognostic impact).

CONCLUSIONS

The evaluation of RRM1 gene expression in cfRNA allows for estimation of the risk of severe OM in patients subjected to RTH.

摘要

背景

头颈部癌症(HNC)的强化治疗:通常结合细胞毒性药物进行放射治疗(RTH)与口腔粘膜炎(OM)有关。核苷酸合成途径(RNR1,由 RRM1 基因编码)功能的改变可以调节细胞 DNA 修复机制的效率,并影响 HNC 患者在 RTH 后 OM 的发生和严重程度的风险。

目的

本研究旨在评估游离循环 RNA(cfRNA)中测量的 RRM1 基因表达与接受 RTH 治疗的 HNC 患者更严重的 OM 风险、无病生存(DFS)和总生存(OS)之间的相关性。

方法

该研究纳入了 60 名接受 RTH 治疗的 HNC 患者。在接受治疗前,从外周血血浆中分离出循环 RNA ,检测 RRM1 基因的表达。

结果

高 RRM1 基因表达与 RTH 后 5(OR=4.97)、6(OR=4.33)和 7(OR=3.50)周时 3 级 OM 的风险显著相关。RRM1 基因的表达与 DFS 和 OS 缩短的风险无显著相关性(然而,分离良好的 Kaplan-Meier 曲线可能表明其具有潜在的预后影响)。

结论

cfRNA 中 RRM1 基因表达的评估可用于估计接受 RTH 的患者发生严重 OM 的风险。

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