Identification of SLC38A7 as a Prognostic Marker and Potential Therapeutic Target of Lung Squamous Cell Carcinoma

Naoki Haratake, Qingjiang Hu, Tatsuro Okamoto, Tomoko Jogo, Gouji Toyokawa, Fumihiko Kinoshita, Tomoyoshi Takenaka, Tetsuzo Tagawa, Norifumi Iseda, Shinji Itoh, Yuichi Yamada, Yoshinao Oda, Mototsugu Shimokawa, Chie Kikutake, Mikita Suyama, Motoko Unoki, Hiroyuki Sasaki, Masaki Mori

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: No effective molecular targeted therapy has been established for squamous cell lung cancer (SCC). We conducted a comprehensive study of SCC patients using RNA-sequencing and The Cancer Genome Atlas (TCGA) dataset in order to clarify the driver oncogene of SCC.

METHOD: Forty-six samples of 23 patients were totally analyzed with RNA-sequencing. We then searched for candidate-oncogenes of SCC using the TCGA database. To identify candidate oncogenes, we used the following two criteria: 1) the genes of interest were 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 using the TCGA dataset, the DNA copy number of the genes was positively correlated with the mRNA expression.

RESULT: We identified 188 candidate-oncogenes. Among those, the high expression of SLC38A7 was a strong prognostic marker that was significantly associated with a poor prognosis in terms of both overall survival (OS) and recurrence-free survival in the TCGA dataset (p < 0.05). Additionally, 202 resected SCC specimens were also subjected to an immunohistochemical analysis. Patients with the high expression of SLC38A7 (alternative name is SNAT7) protein showed significantly shorter OS in comparison to those with the low expression of SLC38A7 protein (median OS 3.9 years [95% CI, 2.4-6.4 years] vs. 2.2 years [95% CI, 1.9-4.1 years]; log rank test: p = 0.0021).

CONCLUSION: SLC38A7, which is the primary lysosomal glutamine transporter required for the extracellular protein-dependent growth of cancer cells, was identified as a candidate therapeutic target of SCC.

Original languageEnglish
JournalAnnals of surgery
DOIs
Publication statusE-pub ahead of print - Jun 18 2021

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