MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis

被引:202
作者
Gao, Wen [1 ]
Shen, Hua [1 ]
Liu, Lingxiang [1 ]
Xu, Jian [2 ]
Xu, Jing [1 ]
Shu, Yongqian [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing 210029, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Clin Lab, Nanjing 210029, Peoples R China
关键词
MiR-21; Microarray; Prognosis; QRT-PCR; Real-time PCR; Squamous cell lung carcinoma; MICRORNA EXPRESSION; REDUCED EXPRESSION; COLORECTAL-CANCER; BREAST-CANCER; METASTASIS; PROFILES; SURVIVAL; INVASION; PDCD4; SIGNATURES;
D O I
10.1007/s00432-010-0918-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study compared miRNA expression patterns in primary squamous cell lung carcinoma specimens with those of matched normal lung tissue in order to determine their potential relevance to clinicopathological factors and patient postoperative survival times. Locked nucleic acids miRNA microarray expression profiling was performed on four matched pairs of tissues. After microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR) (real-time PCR), miR-21 was selected for further TaqMan real-time PCR study in 30 matched tissue pairs. Seven miRNAs of hsa-miR-21, hsa-miR-31, hsa-miR-34a, hsa-miR-22*, hsa-miR-504, hsa-miR-18a, and hsa-miR-412 were observed to be upregulated greater than twofold in the squamous cell lung carcinoma tissues compared with normal tissues, whereas 23 miRNAs of hsa-miR-30a, hsa-miR-30d, hsa-miR-126, hsa-miR-652, hsa-miR-100, hsa-miR-143, hsa-miR-130a, hsa-miR-145, hsa-miR-30e, hsa-miR-126*, hsa-miR-181a, hsa-miR-125b, hsa-miR-886-3p, hsa-miR-451, hsa-miR-29c, hsa-miR-26b, hsa-miR-101, hsa-miR-320, hsa-miR-30b, hsa-miR-886-5p, hsa-miR-29a, hsa-miR-26a, and hsa-miR-99a were found to be downregulated greater than twofold. MiR-21 was overexpressed in 73.3% of the squamous cell lung carcinoma specimens examined (P = 0.022). The relationship between the miR-21 expression level and various clinicopathologic factors was also analyzed. High-level expression of miR-21 was significantly correlated with shortened survival time (P = 0.022, log-rank test; Kaplan-Meier). Multivariate Cox proportional hazard regression analysis revealed this significant prognostic impact (P = 0.000; HR 1.293; 95% CI 1.123-1.489) to be independent of clinical disease stage (P = 0.013; HR 2.660; 95% CI 1.229-5.758) and other clinicopathologic factors. Expression patterns of miRNAs were found to be systematically altered in squamous cell lung carcinoma tissue. High miR-21 expression is associated with shortened survival time, indicating that miR-21 may serve as a molecular diagnostic and prognostic marker for patients with squamous cell lung carcinoma.
引用
收藏
页码:557 / 566
页数:10
相关论文
共 39 条
[1]  
[Anonymous], 2002, AJCC CANC STAGING HD
[2]   MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer [J].
Asangani, I. A. ;
Rasheed, S. A. K. ;
Nikolova, D. A. ;
Leupold, J. H. ;
Colburn, N. H. ;
Post, S. ;
Allgayer, H. .
ONCOGENE, 2008, 27 (15) :2128-2136
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   MicroRNAs modulate the chemosensitivity of tumor cells [J].
Blower, Paul E. ;
Chung, Ji-Hyun ;
Verducci, Joseph S. ;
Lin, Shili ;
Park, Jong-Kook ;
Dai, Zunyan ;
Liu, Chang-Gong ;
Schmittgen, Thomas D. ;
Reinhold, William C. ;
Croce, Carlo M. ;
Weinstein, John N. ;
Sadee, Wolfgang .
MOLECULAR CANCER THERAPEUTICS, 2008, 7 (01) :1-9
[5]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[6]   MicroRNA-cancer connection: The beginning of a new tale [J].
Calin, George Adrian ;
Croce, Carlo Maria .
CANCER RESEARCH, 2006, 66 (15) :7390-7394
[7]   A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA) [J].
Castoldi, M ;
Schmidt, S ;
Benes, V ;
Noerholm, M ;
Kulozik, AE ;
Hentze, MW ;
Muckenthaler, MU .
RNA, 2006, 12 (05) :913-920
[8]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[9]  
Chan SH, 2008, ANTICANCER RES, V28, P907
[10]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9