J Cancer 2016; 7(12):1610-1620. doi:10.7150/jca.14923

Research Paper

MicroRNA Expression Profile on Solid Subtype of Invasive Lung Adenocarcinoma Reveals a Panel of Four miRNAs to Be Associated with Poor Prognosis in Chinese Patients

Yong-Qiang Zhang1,*, Wei-Ya Wang2,*, Jian-Xin Xue3, Yan Xu1, Ping Fan1, Bennett Adam Caughey4, Wei-Wei Tan1, Gui-Qun Cao5, Li-Li Jiang2, You Lu3, Kang Zhang4,5,6, Xun Hu1✉

1. Biorepository, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
2. Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China
3. Department of Thoracic Oncology and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
4. Institute for Genomic Medicine, University of California, San Diego, San Diego, CA 92093, USA
5. Molecular Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, China
6. Department of Ophthalmology, University of California, San Diego, San Diego, CA 92093, USA.
*These two authors contribute to this article equally.

Abstract

According to the reclassification of lung adenocarcinoma (LAC) proposed in 2011, solid predominant lung adenocarcinoma (SPA) has been associated with poor outcomes for LAC patients. However, the prognostic value of the presence of solid subtype remains unclear. Besides, there is little data about the roles of microRNA (miRNA) in solid subtype of LAC. In this study, 243 LAC patients were classified into solid subtype positive and negative groups (S+ LAC, n=134 and S- LAC, n=109) according to whether the solid subtype was more than 5% of the tumor component or not. We analyzed the relationship between solid subtype and patients' outcome by univariate and multivariate analyses. Solid subtype was proved to be significantly associated with the 5-year overall survival and played as an independent prognostic factor for stage I-III invasive LAC patients. Then miRNA microarray was used to identify differentially expressed miRNAs in solid subtype, resulting in 31 differential miRNAs. Quantitative reverse transcription-PCR (QRT-PCR) was used to validate 4 key miRNAs (miR-133b, miR-155-5p, miR-124-3p, miR-145-5p). Further, CCK-8 and transwell assays were performed to validate the impact of one dysregulated miRNA (miR-133b) on LAC cell function. Interestingly, while miR-133b could significantly inhibit the proliferation of A549 and SPC-A1, it showed no effect on the migration or invasion of LAC cell lines. These results suggest that solid subtype can exert independent prognostic impact on LAC patients, and 4 important dysregulated miRNAs in solid subtype of LAC may be involved in the malignancy of S+LAC, thus may further have clinical perspective for S+ LAC in the future.

Keywords: Lung adenocarcinoma, stage I-III, Solid subtype, Prognosis, microRNA (miRNA).

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How to cite this article:
Zhang YQ, Wang WY, Xue JX, Xu Y, Fan P, Caughey BA, Tan WW, Cao GQ, Jiang LL, Lu Y, Zhang K, Hu X. MicroRNA Expression Profile on Solid Subtype of Invasive Lung Adenocarcinoma Reveals a Panel of Four miRNAs to Be Associated with Poor Prognosis in Chinese Patients. J Cancer 2016; 7(12):1610-1620. doi:10.7150/jca.14923. Available from http://www.jcancer.org/v07p1610.htm