MiRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer.

Abstract

PURPOSE:

To investigate the possible role of microRNAs in the resistance to platinum based chemotherapy in non-small cell lung cancer (NSCLC), explore their potential role and find potential biomarkers for prediction of the response to platinum.

RESULTS:

21 miRNAs were deregulated in A549/CDDP. Increased miR-21 expression significantly increased the resistance of A549 cell to platinum, whereas reduced miR-21 decreased the resistance of A549/CDDP cell. This finding was further validated in the tissue samples of 58 patients and it was found that miR-21 expression was significantly increased in platinum based chemotherapy-resistant patients (n = 58, p = 0.000). And increased miR-21 expression was associated with the shorter DFS (p = 0.008). Among these 58 patients, 32 had the corresponding plasma samples and similar tendencies were detected in 68.75% patients. Finally, transfection of A549/CDDP with anti-miR-21 increased the expression of PTEN and decreased Bcl-2. In contrast, pre-miR-21 decreased the expression of PTEN and increased Bcl-2 in A549.

PATIENTS AND METHODS:

Microarray was employed to compare the expression of miRNAs between A549 and A549/CDDP cells. The effect of a differently expressed miRNA (miR-21) was examined on the sensitivity of cells to platinum. MiR-21 expression in NSCLC tumor tissues and matched plasma sample was also analyzed by Real-time PCR.

CONCLUSION:

Our data suggests that the expression level of miR-21 in tumor tissue and plasma might be used as a biomarker to predict adjuvant platinum based chemotherapy response and disease free survival in patients with NSCLC. Thus, it may serve as a novel therapeutic target to modulate platinum-based chemotherapy.

• Authors: Wen Gao, Xiao Lu, Lingxiang Liu, Jing Xu, Dongjie Feng, Yongqian Shu
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 13 Issue 5 Pg. 330-40 (Mar 2012) ISSN: 1555-8576 [Electronic] United States
• PMID: 22237007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• MIRN21 microRNA, human
• MicroRNAs
• Organoplatinum Compounds

Topics

• Biomarkers, Tumor (biosynthesis, genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Drug Resistance, Neoplasm
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• MicroRNAs (biosynthesis, genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Organoplatinum Compounds (pharmacology)