Preoperative Prediction of Lymph Node Status by Circulating Mir-18b and Mir-20a During Chemoradiotherapy in Patients with Rectal Cancer

Preoperative Prediction of Lymph Node Status by Circulating Mir-18b and Mir-20a During Chemoradiotherapy in Patients with Rectal Cancer
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DOI:
10.1007/s00268-015-3083-8
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发表时间:
2015-09-01
影响因子:
2.6
通讯作者:
Gaedcke, Jochen
Gaedcke, Jochen
中科院分区:
医学3区
文献类型:
--
作者:
Azizian, Azadeh;Kramer, Frank;Gaedcke, Jochen

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在局部晚期直肠癌中,术前放化疗(CRT)的治疗成功范围从耐药性到完全消退。对于那些对CRT反应良好的患者,目前正在研究局部切除(LR)手术,以尽量减少手术并发症并改善功能预后。为了保持肿瘤的益处,适当的分期程序是必不可少的。然而,目前的临床评估和影像学技术有待进一步改进。采用qPCR方法分析直肠癌患者(n = 42)血浆中与直肠癌相关的5种mirna (miR-17、miR-18b、miR-20a、miR-31和miR-193-3p)。在CRT前、中、后评估表达水平,并结合直肠全系膜切除和强化组织病理学检查后患者的淋巴结状况进行分析。五个mirna中的四个在血浆中显示了可靠的结果。miR-31因低表达而被排除。MicroRNA-17、18b、20a和193-3p在不同时间点的表达水平发生改变。只有43% (miR-17)、43% (miR-18b)、53% (miR-20a)和60% (miR-193-3p)的miRNA表达持续升高或降低。CRT期间miR-18b和miR-20a表达降低与术后淋巴结阴性有显著相关性(p < 0.05)。术前CRT患者血浆中MicroRNA表达的变化。这种改变不是连续的,其意义需要对更大的患者群体进行额外的分析。如果前瞻性验证,术前CRT后miR-18b和miR-20a表达降低与淋巴结阴性同时出现,有助于对全肠系膜切除和LR的手术方式进行分层。
In locally advanced rectal cancer, therapeutic success of preoperative chemoradiotherapy (CRT) ranges from resistance to complete regression. For those patients that respond well to CRT, local resection (LR) procedures are currently under investigation to minimize surgical morbidity and to improve functional outcome. To maintain the oncologic benefit appropriate staging procedures are essential. However, current clinical assessment and imaging techniques need further improvement.Five miRNAs associated with rectal cancer (miR-17, miR-18b, miR-20a, miR-31, and miR-193-3p) were analyzed in the plasma of rectal cancer patients (n = 42) using qPCR. Expression levels were assessed before, during and after CRT and analyzed in regard to patients' lymph node status obtained after total mesorectal excision and intensive histopathological work-up.Four of the five miRNAs revealed reliable results in the plasma. miR-31 was excluded due to its low expression. MicroRNA-17, 18b, 20a, and 193-3p showed altering expression levels at different time points. Only 43 % (miR-17), 43 % (miR-18b), 53 % (miR-20a), and 60 % (miR-193-3p) showed a continuous in- or decrease of miRNA expression. The reduced expression of miR-18b and miR-20a during CRT was found to be significantly associated with postoperative lymph node negativity (p < 0.05).MicroRNA expression in patient plasma changes during preoperative CRT. The alteration is not continuous and the meaning requires additional analysis on a larger patient cohort. The co-occurrence of reduced miR-18b and miR-20a expression with lymph node negativity after preoperative CRT could help to stratify the surgical procedure with respect to total mesorectal excision and LR if validated prospectively.