The Clinical Significance of MiR-429 as a Predictive Biomarker in Colorectal Cancer Patients Receiving 5-Fluorouracil Treatment

被引:37
作者
Dong, Sheng-jian [1 ]
Cai, Xiao-jun [2 ]
Li, Shu-jin [1 ]
机构
[1] Second Peoples Hosp Hefei City, Dept Lab, Hefei, Anhui, Peoples R China
[2] Second Peoples Hosp Hefei City, Dept Obstet & Gynaecol, Hefei, Anhui, Peoples R China
来源
MEDICAL SCIENCE MONITOR | 2016年 / 22卷
基金
中国国家自然科学基金;
关键词
Antineoplastic Agents; Colorectal Neoplasms; Fluorouracil; MicroRNAs; CIRCULATING MICRORNAS; APOPTOSIS; OXALIPLATIN; EXPRESSION; FLUOROURACIL; METASTASIS; LEUCOVORIN; CARCINOMA; ADJUVANT; SURVIVAL;
D O I
10.12659/MSM.900674
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: 5-Fluorouracil (5-FU) based treatment is the standard therapy for metastatic colorectal cancer (CRC), but the development of chemoresistance is inevitable. Increasing evidence shows that dysregulation of microRNAs (miRNAs) is involved in malignant transformation. Thus, it is imperative that we find new diagnostic and prognostic marker for chemotherapy in CRC. Material/Methods: For clinical parameter analysis, 78 CRC tissues and adjacent normal tissues and 45 serum specimens from CRC patients were included in this study. For chemo-response analysis, 116 primary tissues were collected from the patients receiving first-line 5-FU treatment. Quantitative Real-Time PCR (qRT-PCR) was used to detect microRNAs expression. Results: The expression of miR-429 was significantly increased in both serum and primary tissues from CRC patients, and enhanced miR-429 level was associated with tumor size, lymph node metastasis, and TNM stage. The diagnostic and prognostic values were also confirmed in CRC by using primary tissues. For patients receiving 5-FU-based treatment, miR-429 levels were significantly lower in responding group. The proportions of patients that did not experience response to therapy were higher in primary tumors with high miR-429 expression levels as compared with primary tumors with low miR-429 expression levels. Finally, Kaplan-Meier survival analysis showed that miR-429 is an independent prognostic indicator for chemo-response to 5-FU therapy among CRC patients. Conclusions: High level of miR-429 expression was correlated with enhanced malignant potential and poor prognosis of CRC patients. Furthermore, miR-429 could affect the chemo-sensitivity of CRC patients to 5-FU therapy and was associated with poor response to 5-FU-based chemotherapy in patients with CRC.
引用
收藏
页码:3352 / 3361
页数:10
相关论文
共 28 条
[1]   Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study [J].
Andre, Thierry ;
de Gramont, Armand ;
Vernerey, Dewi ;
Chibaudel, Benoist ;
Bonnetain, Franck ;
Tijeras-Raballand, Annemilai ;
Scriva, Aurelie ;
Hickish, Tamas ;
Tabernero, Josep ;
Van Laethem, Jean Luc ;
Banzi, Maria ;
Maartense, Eduard ;
Shmueli, Einat ;
Carlsson, Goran U. ;
Scheithauer, Werner ;
Papamichael, Demetris ;
Moeehler, Marcus ;
Landolfi, Stefania ;
Demetter, Pieter ;
Colote, Soudhir ;
Tournigand, Christophe ;
Louvet, Christophe ;
Duval, Alex ;
Flejou, Jean-Francois ;
de Gramont, Aimery .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (35) :4176-+
[2]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[3]   Role for a bidentate ribonuclease in the initiation step of RNA interference [J].
Bernstein, E ;
Caudy, AA ;
Hammond, SM ;
Hannon, GJ .
NATURE, 2001, 409 (6818) :363-366
[4]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[5]   MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes [J].
Cantini, Laura ;
Isella, Claudio ;
Petti, Consalvo ;
Picco, Gabriele ;
Chiola, Simone ;
Ficarra, Elisa ;
Caselle, Michele ;
Medico, Enzo .
NATURE COMMUNICATIONS, 2015, 6
[6]   MicroRNAs as oncogenes and tumor suppressors [J].
Chen, CZ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1768-1771
[7]   Deregulation of miR-200b, miR-200c and miR-429 indicates its potential relevant role in patients with colorectal cancer liver metastasis [J].
Cristobal, Ion ;
Rincon, Raul ;
Manso, Rebeca ;
Carames, Cristina ;
Aguilera, Oscar ;
Madoz-Gurpide, Juan ;
Rojo, Federico ;
Garcia-Foncillas, Jesus .
JOURNAL OF SURGICAL ONCOLOGY, 2014, 110 (04) :484-485
[8]   A Randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer [J].
Goldberg, RM ;
Sargent, DJ ;
Morton, RF ;
Fuchs, CS ;
Ramanathan, RK ;
Williamson, SK ;
Findlay, BP ;
Pitot, HC ;
Alberts, SR .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (01) :23-30
[9]   Long noncoding RNAs: Novel players in colorectal cancer [J].
Han, Dong ;
Wang, Meng ;
Ma, Ning ;
Xu, Ya ;
Jiang, Yuting ;
Gao, Xu .
CANCER LETTERS, 2015, 361 (01) :13-21
[10]   miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer [J].
Karaayvaz, M. ;
Zhai, H. ;
Ju, J. .
CELL DEATH & DISEASE, 2013, 4 :e659-e659