Dong Wei, Li Baosheng, Wang Juan, Song Yipeng, Zhang Zicheng, Fu Chengrui, Zhang Peiliang
School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China.
Oncol Rep. 2016 Mar;35(3):1449-56. doi: 10.3892/or.2015.4499. Epub 2015 Dec 21.
MicroRNA-7 has been reported to participate in tumorigenesis and progression by several signaling pathways in various tumors. However, its potential as a serum diagnostic factor and predictive biomarker for esophageal squamous cell carcinoma (ESCC) has not been studied. Serum samples were collected from 105 pathologically proven ESCC patients and 30 age- and gender-matched healthy controls. All patients were treated with concurrent chemoradiotherapy (CRT). Real‑time polymerase chain reaction was carried out to measure the serum miR-7 expression level. The data were compared among radio-sensitive and radio-resistant groups, and healthy volunteers to elucidate the diagnostic and predictive value of miR-7 expression. Finally, in vitro experiments are used to clarify the mechanisms of the miR-7. In the present study, we found that the serum miR-7 level of ESCC patients was 4.74-fold lower as compared with healthy subjects, indicating that serum miR-7 expression could be an excellent diagnostic factor. The serum miR-7 expression level for these responsive patients was 2.34‑fold higher than that for non-responsive patients, indicating it as a valuable biomarker for predicting treatment response of ESCC patients to concurrent chemoradiation treatment. We also found that miR-7 levels are strongly correlated with tumor length and the status of lymph node metastasis (P<0.05). In contrast, the responsiveness of therapy is significantly correlated with CEA (P<0.05), Cyfra21-1 (P<0.05), serum miR-7 level (P<0.05) and myelosuppression (P<0.01). In addition, the experimental data also suggest that miR-7 can interfere with EGFR mRNA translation. In ESCC patients, serum miR-7 has the potential to serve as a noninvasive biomarker of diagnosis and predicting treatment responses to concurrent chemoradiation therapy. ESCC patients with lower Cyfra21-1 and CEA, higher miR-7 and severe myelosuppression were much more sensitive to CRT. In addition, miR-7 may function by interfering with EGFR mRNA translation, but not degradation.
据报道，微小RNA-7通过多种信号通路参与各种肿瘤的发生和发展。然而，其作为食管鳞状细胞癌（ESCC）血清诊断因子和预测生物标志物的潜力尚未得到研究。收集了105例经病理证实的ESCC患者和30例年龄及性别匹配的健康对照者的血清样本。所有患者均接受同步放化疗（CRT）。采用实时聚合酶链反应检测血清miR-7表达水平。对放射敏感组和放射抵抗组以及健康志愿者的数据进行比较，以阐明miR-7表达的诊断和预测价值。最后，通过体外实验阐明miR-7的作用机制。在本研究中，我们发现ESCC患者的血清miR-7水平比健康受试者低4.74倍，表明血清miR-7表达可能是一个优秀的诊断因子。这些反应性患者的血清miR-7表达水平比无反应患者高2.34倍，表明其是预测ESCC患者同步放化疗治疗反应的有价值生物标志物。我们还发现miR-7水平与肿瘤长度和淋巴结转移状态密切相关（P<0.05）。相比之下，治疗反应与癌胚抗原（CEA，P<0.05）、细胞角蛋白19片段（Cyfra21-1，P<0.05）、血清miR-7水平（P<0.05）和骨髓抑制（P<0.01）显著相关。此外，实验数据还表明miR-7可干扰表皮生长因子受体（EGFR）mRNA的翻译。在ESCC患者中，血清miR-7有潜力作为诊断和预测同步放化疗治疗反应的非侵入性生物标志物。Cyfra21-1和CEA水平较低、miR-7水平较高且骨髓抑制严重的ESCC患者对CRT更为敏感。此外，miR-7可能通过干扰EGFR mRNA的翻译而非降解发挥作用。
