TMEM158 and FBLP1 as novel marker genes of cisplatin sensitivity in non-small cell lung cancer cells

ABSTRACTEven after development of molecular targeting therapies, platinum-based chemotherapy is still a standard care for treatment of locally advanced non-small cell lung cancer (NSCLC). So far, critical molecular markers capable to predict the therapeutic response in NSCLC patients remain undeterm...

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Published in:Experimental lung research 2012-11, Vol.38 (9-10), p.463-474
Main Authors: Mohammed, Ahmed El Sayed, Eguchi, Hidetaka, Wada, Satoru, Koyama, Nobuyuki, Shimizu, Michio, Otani, Keiko, Ohtaki, Megu, Tanimoto, Keiji, Hiyama, Keiko, Gaber, Mohammed Soliman, Nishiyama, Masahiko
Format: Article
Language:English
Subjects:
Antineoplastic Agents - therapeutic use
Biomarkers, Tumor - metabolism
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Cell Adhesion Molecules - metabolism
Cell Line, Tumor
Cisplatin - therapeutic use
cisplatin-chemotherapy
Cytoskeletal Proteins - metabolism
Drug Resistance, Neoplasm - genetics
Gene Expression
Gene Knockdown Techniques
Humans
Inhibitory Concentration 50
KEYWORDS
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Membrane Proteins - metabolism
microarray
NSCLC
predictive marker
Regression Analysis
Tumor Suppressor Proteins - metabolism
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Summary:ABSTRACTEven after development of molecular targeting therapies, platinum-based chemotherapy is still a standard care for treatment of locally advanced non-small cell lung cancer (NSCLC). So far, critical molecular markers capable to predict the therapeutic response in NSCLC patients remain undetermined. We here attempted to identify novel biomarker genes for cisplatin (CDDP) for a tailored therapy. Initial screening to explorer association of IC50 values of CDDP obtained by MTT assay and gene expression levels measured with oligonucleotide microarray and real-time RT-PCR provided 6 candidate genes, namely, NUBPL, C9orf30, ZNF12, TMEM158, GSK3B, and FBLP1 using 9 lung cancer cells consisting of 3 small and 6 NSCLC cells. These 6 genes together with 5 reported biomarkers, i.e., GSTP1, ERCC1, BRCA1, FRAP1, and RRM1, were subjected to a linear regression analysis using 12 NSCLC cell lines including 6 additional NSCLC cells: only FBLP1 and TMEM158 genes showed positive associations with statistical significances (P = .016 and .026, respectively). The biological significance of these genes was explored by in vitro experiments: Knockdown experiments in PC-9/CDDP cells revealed that the reduced expression of TMEM158 significantly decreased the chemo-resistance against CDDP (P
ISSN:0190-2148
1521-0499
DOI:10.3109/01902148.2012.731625