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Int J Clin Exp Pathol 2013;6(12):2745-2756

Original Article
Potential biomarkers for paclitaxel sensitivity in hypopharynx cancer cell

Cheng-Zhi Xu, Run-Jie Shi, Dong Chen, Yi-Yuan Sun, Qing-Wei Wu, Tao-Wang, Pei-Hua Wang

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University,
Shanghai, China

Received October 6, 2013; Accepted November 3, 2013; Epub November 15, 2013; Published December 1, 2013

Abstract: Paclitaxel has been proved to be active in treatment and larynx preservation of HNSCC, however, the fact that about 20-40% patients
do not respond to paclitaxel makes it urgent to figure out the biomarkers for paclitaxel-based treatment in Hypopharynx cancer (HPC) patients to
improve the therapy effect. In this work, Fadu cells, treated or untreated with low dose of paclitaxel for 24 h, were applied to DNA microarray
chips. The differential expression in mRNAs and miRs was analyzed and the network between expression-altered mRNAs and miRs was
constructed. Differentially expressed genes were mainly enriched in superpathway of cholesterol biosynthesis (ACAT2, MSMO1, LSS, FDFT1
and FDPS etc.), complement system (C3, C1R, C1S, CFR and CFB etc.), interferon signaling (IFIT1, IFIT3, IFITM1 and MX1 etc.), mTOR
signaling (MRAS, PRKAA2, PLD1, RND3 and EIF4A1 etc.) and IGF1 signaling (MRAS, IGFBP7, JUN and FOS etc.), most of these pathways are
implicated in tumorigenesis or chemotherapy resistance. The first three pathways were predicted to be suppressed, while the last two
pathways were predicted to be induced by paclitaxel, suggesting the combination therapy with mTOR inhibition and paclitaxel might be better
than single one. The dramatically expression-altered miRs were miR-112, miR-7, miR-1304, miR-222*, miR-29b-1* (these five miRs were
upregulated) and miR-210 (downregulated). The 26 putative target genes mediated by the 6 miRs were figured out and the miR-gene network
was constructed. Furthermore, immunoblotting assay showed that ERK signaling in Fadu cells was active by low dose of paclitaxel but
repressed by high dose of paclitaxel. Collectively, our data would provide potential biomarkers and therapeutic targets for paclitaxel-based
therapy in HPC patients. (IJCEP1310018).

Keywords: Paclitaxel, hypopharynx cancer, DNA microarray, mTOR signaling

Address correspondence to: Dr. Pei-Hua Wang, Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital,
School of Medicine, Shanghai Jiao Tong University, No. 639 Zhizaoju Road, Shanghai, 200011, China. Tel: +86-21-23271699-5101; E-mail:
wangpeihua0707@126.com