Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center. 333 Cottman Avenue, Philadelphia, PA, 19111, USA.
Sci Rep. 2023 Aug 30;13(1):14237. doi: 10.1038/s41598-023-41030-7.
Treatment with 5-fluorouracil (5-FU) based therapy is still used for colorectal cancer (CRC). Epigenetics has become a focus of study in cancer because of its reversibility besides its known regulatory functions. In this study, we will monitor the change in microRNAs (miRNAs) levels with 5-FU-based therapy at baseline and after 3 and 6 months of treatment to be correlated with their prognostic potential. The expression levels of 5 miRNAs, namely miRNA223-3p, miRNA20a-5p, miRNA17-5p, miRNA19a-3p, and miRNA7-5p, were measured in the peripheral blood of 77 CRC patients, along with the expression of 3 proteins PTEN, ERK, and EGFR. At baseline, CRC patients had significantly higher levels of circulating miRNAs than healthy controls. This level was reduced after 3 months of 5-FU-based therapy, then increased after 6 months significantly in responder patients compared to non-responders. MiRNA19a-3p showed that significant pattern of change in the subgroups of patients with high ERK, EGFR, and PTEN protein levels, and its 6 months level after 5-FU-based therapy showed significance for the hazard of increased risk of disease recurrence and progression.
5-氟尿嘧啶（5-FU）为基础的治疗仍用于结直肠癌（CRC）。由于其已知的调节功能之外的可逆性，表观遗传学已成为癌症研究的焦点。在这项研究中，我们将在基线时以及治疗 3 个月和 6 个月后监测基于 5-FU 的治疗中 microRNAs（miRNAs）水平的变化，以将其与预后潜力相关联。我们在 77 名 CRC 患者的外周血中测量了 5 种 miRNA（miRNA223-3p、miRNA20a-5p、miRNA17-5p、miRNA19a-3p 和 miRNA7-5p）的表达水平，同时还测量了 3 种蛋白质（PTEN、ERK 和 EGFR）的表达水平。在基线时，CRC 患者的循环 miRNA 水平明显高于健康对照组。这种水平在基于 5-FU 的治疗 3 个月后降低，然后在应答者患者中在 6 个月后显著增加，与无应答者相比。miRNA19a-3p 在 ERK、EGFR 和 PTEN 蛋白水平较高的患者亚组中显示出明显的变化模式，并且其在基于 5-FU 的治疗 6 个月后的水平对疾病复发和进展风险增加的危险具有显著性。
