Identification Of Slc38a7 As A Prognostic Marker And Potential Targeted Driver Gene Of Lung Squamous Cell Carcinomas
*Naoki Haratake1, *Qingjiang Hu1, *Tatsuro Okamoto2, *Tomoko Jogo1, *Tetsuzo Tagawa1, *Yoshinao Oda3, *Chie Kikutake4, *Mikita Suyama1, *Motoko Unoki5, *Hiroyuki Sasaki5, *Motosugu Shimokawa6, Masaki Mori1
1Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan2Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan3Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan4Department of Systems Life Sciences, Graduate School of Systems Life Sciences and Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan5Division of Epigenomics, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Fukuoka, Japan6Department of Biostatistics, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
OBJECTIVE(S): We conducted a comprehensive study of squamous cell carcinomas (SCC) patients using RNA-seq and TCGA dataset in order to clarify the driver oncogene of SCC regardless of the amount of smoking.
METHODS: Forty-six samples of 23 patients were analyzed with RNA-seq. We then searched for candidate-oncogenes of each non-light smoker (≤30 pack years) and heavy smoker (>30 pack years) using the TCGA database together.
RESULTS: To identify the candidate oncogenes, we used the following two criteria: 1) the genes of interest had to be overexpressed in tumor tissues of SCC patients in comparison to normal tissues; and 2) using an integrated mRNA expression and DNA copy number profiling analysis from TCGA, the DNA copy number of the genes had to be positively correlated with the mRNA expression . We identified 188 common candidate genes. Among these, in TCGA data set, SLC38A7 was the only prognostic marker that was associated with a significantly poor prognosis. Immunohistochemistry for 203 resected SCC specimens was additionally performed. The SLC38A7 protein-positive group showed significantly shorter OS in comparison to the negative group (median OS 3.9 vs. 2.2 years, p=0.0006).
CONCLUSIONS: SLC38A7, which was previously reported to code the primary lysosomal glutamine exporter required for the extracellular protein-dependent growth of cancer cells, was identified as a candidate oncogene of SCC.
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