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探索 microRNA 模式作为结直肠癌患者 FOLFOX 化疗诱导周围神经病变的生物标志物。

Exploring microRNA patterns as biomarkers of FOLFOX chemotherapy-induced peripheral neuropathy in patients with colorectal cancer.

机构信息

Department of Biomedical Laboratory Science, Gimcheon University, Gimcheon 39528, Republic of Korea; Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea.

Department of Internal Medicine, Pusan National University College of Medicine, Yangsan 50612, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167209. doi: 10.1016/j.bbadis.2024.167209. Epub 2024 May 1.

Abstract

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.

摘要

FOLFOX 是一种化疗药物(5-氟尿嘧啶、亚叶酸钙和奥沙利铂)的组合,用于治疗晚期结直肠癌(CRC),但会引起各种副作用。化疗引起的周围神经病变(CIPN)是最严重的副作用之一,会降低接受 FOLFOX 化疗的 CRC 患者的生活质量。本研究旨在评估循环 miRNA、皮质醇和儿茶酚胺作为潜在生物标志物,以预测 FOLFOX-CIPN 症状。对 8 例接受 FOLFOX 化疗的 CRC 患者血浆中循环的 RNA 进行了高通量 miRNA 测序。根据两组患者(接受≤3 个周期和接受≥6 个周期的 FOLFOX 化疗的患者)评估 miRNA 表达谱。在 27 例接受 FOLFOX 化疗的 CRC 患者中使用定量逆转录聚合酶链反应验证了这些 miRNA。使用生物信息学和功能分析预测靶基因。使用酶联免疫吸附试验测量外周血浆中的皮质醇和儿茶酚胺浓度。当比较接受≤3 和≥6 个周期 FOLFOX 化疗的两组之间的 miRNA 表达时,miR-3184-5p 差异表达。接受≥6 个周期 FOLFOX 化疗的组的皮质醇水平显著高于接受≤3 个周期的组。这项研究表明,miR-3184-5p 可能是预测 CIPN 的潜在标志物。

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