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miR-181c的高表达作为II期结直肠癌复发的预测标志物。

High expression of miR-181c as a predictive marker of recurrence in stage II colorectal cancer.

作者信息

Yamazaki Nobuyoshi, Koga Yoshikatsu, Taniguchi Hirokazu, Kojima Motohiro, Kanemitsu Yukihide, Saito Norio, Matsumura Yasuhiro

机构信息

Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan.

Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

出版信息

Oncotarget. 2017 Jan 24;8(4):6970-6983. doi: 10.18632/oncotarget.14344.

Abstract

INTRODUCTION

A standard treatment for stage II colorectal cancer (CRC) is surgical resection without adjuvant chemotherapy. However, the recurrence rate of these patients is approximately 20%. To date, there are no robust biomarkers suitable for predicting recurrence in stage II CRC patients. In this study, microRNAs (miRNAs) extracted from CRC tissues were examined for a possible biomarker to predict recurrence in stage II CRC patients.

RESULTS

From the comprehensive analysis, 15 miRNAs were selected as candidates for further study. Regarding let-7a, -7d, -7e, miR-23c, -26b, -128a, -151-5p, and -181c, recurrence rates in training cohort patients with higher expression of these miRNAs isolated from their frozen tissues samples were significantly higher than those with lower expression (P < 0.05). According to multivariate analysis, the higher expression of miR-181c was detected as an independent predictive factor of recurrence (P = 0.001, OR: 9.43, 95% CI: 2.57-34.48). Results were similar in miR-181c extracted from FFPE tissues obtained from the training cohort (P = 0.003, OR: 7.46, 95% CI: 1.97-28.57). In the validation cohort using FFPE tissues, the recurrence rate in patients with higher miR-181c expression was significantly higher than those with lower miR-181c expression (P < 0.001).

MATERIALS AND METHODS

Comprehensive analysis using a highly sensitive miRNA chip was initially performed to select candidate miRNAs associated with recurrence. Candidate miRNAs were analyzed by real-time RT-PCR using RNA from frozen and formalin-fixed, paraffin-embedded (FFPE) tissues.

CONCLUSIONS

Higher expression of miR-181c may be a useful recurrence predictor of stage II CRC patients.

摘要

引言

II期结直肠癌(CRC)的标准治疗方法是手术切除,无需辅助化疗。然而,这些患者的复发率约为20%。迄今为止,尚无适用于预测II期CRC患者复发的可靠生物标志物。在本研究中,对从CRC组织中提取的微小RNA(miRNA)进行检测,以寻找可能用于预测II期CRC患者复发的生物标志物。

结果

通过综合分析,选择了15种miRNA作为进一步研究的候选物。对于let-7a、-7d、-7e、miR-23c、-26b、-128a、-151-5p和-181c,在训练队列中,从其冷冻组织样本中分离出的这些miRNA表达较高的患者的复发率显著高于表达较低的患者(P < 0.05)。根据多变量分析,miR-181c的高表达被检测为复发的独立预测因素(P = 0.001,OR:9.43,95% CI:2.57 - 34.48)。从训练队列获得的福尔马林固定石蜡包埋(FFPE)组织中提取的miR-181c的结果相似(P = 0.003,OR:7.46,95% CI:1.97 - 28.57)。在使用FFPE组织的验证队列中,miR-181c表达较高的患者的复发率显著高于miR-181c表达较低的患者(P < 0.001)。

材料与方法

最初使用高灵敏度miRNA芯片进行综合分析,以选择与复发相关的候选miRNA。使用来自冷冻和福尔马林固定石蜡包埋(FFPE)组织的RNA,通过实时RT-PCR对候选miRNA进行分析。

结论

miR-181c的高表达可能是II期CRC患者有用的复发预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b1/5351683/19a2f96ed433/oncotarget-08-6970-g001.jpg

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