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Int J Clin Exp Pathol 2013;6(9):1734-1746

Original Article
Array analysis for potential biomarker of gemcitabine identification in non-small cell lung
cancer cell lines

Hai-Hong Zhang, Zhi-Yi Zhang, Chun-Li Che, Yi-Fang Mei, Yu-Zhi Shi

Department of rheumatism and immunology, First Clinical Medical College affiliated to Harbin Medical University, Harbin, China; Department of
respiratory medicine, First Clinical Medical College affiliated to Harbin Medical University, Harbin, China

Received May 6, 2013; Accepted August 5, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: Gemcitabine is one of the most widely used drugs for the treatment of advanced Non-small cell lung cancer (NSCLC), but modest
objective response rate of patients to gemcitabine makes it necessary to identify novel biomarkers for patients who can benefit from
gemcitabine-based therapy and to improve the effect of clinical therapy. In this work, 3 NSCLC cell lines displaying different sensitivities to
gemcitabine were applied for mRNA and microRNA (miR) expression chips to figure out the biomarkers for gemcitabine sensitivity. Genes
whose expression increased dramatically in sensitive cell lines were mainly enriched in cell adhesion (NRP2, CXCR3, CDK5R1, IL32 and
CDH2) and secretory granule (SLC11A1, GP5, CD36 and IGF1), while genes with significantly upregulated expression in resistant cell line
were mainly clustered in methylation modification (HIST1H2BF, RAB23 and TP53) and oxidoreductase (TP53I3, CYP27B1 and SOD3). The
most intriguing is the activation of Wnt/β-catenin signaling in gemcitabine resistant NSCLC cell lines. The miR-155, miR-10a, miR-30a, miR-
24-2* and miR-30c-2* were upregulated in sensitive cell lines, while expression of miR-200c, miR-203, miR-885-5p, miR-195 and miR-25*
was increased in resistant cell line. Genes with significantly altered expression and putatively mediated by the expression-changed miRs were
mainly enriched in chromatin assembly (MAF, HLF, BCL2, and IGSF3), anti-apoptosis (BCL2, IGF1 and IKBKB), protein kinase (NRP2, PAK7
and CDK5R1) (all the above genes were upregulated in sensitive cells) and small GTPase mediated signal transduction (GNA13, RAP2A,
ARHGAP5 and RAB23, down-regulated in sensitive cells). Our results might provide potential biomarkers for gemcitabine sensitivity prediction
and putative targets to overcome gemcitabine resistance in NSCLC patients. (IJCEP1305003).

Keywords: Non-small cell lung cancer, gemcitabine, gene expression profiles, miR expression profiles

Address correspondence to: Dr. Yu-Zhi Shi, Department of respiratory medicine, First Clinical Medical College affiliated to Harbin Medical
University, Harbin, China. E-mail: yuzhishi_harbin@163.com