Abstract 1159: Downregulation of TMPRSS11B in squamous cell carcinoma

Abstract

Abstract [Background] Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers. The molecular mechanism of ESCC development has not been fully elucidated. [Aim] The aim of this study is to identify responsible genes for ESCC development. [Materials and Methods] Firstly, we performed transcriptome sequence (RNA-seq) analysis of surgically resected tumor and corresponding normal tissues form 3 ESCC patients with different tumor locus, histrogical differentiation, and TNM stage.by RNA-seq analysis: (Case 1) upper thoracic esophagus, well differentiated SCC, TNM, Stage I; (Case 2) middle thoracic esophagus, poorly differentiated SCC, T3N0M0, Stage II; and (Case 3) lower thoracic esophagus, moderately differentiated SCC, T3N1M0, Stage III. Next, we validated the expression status of the candidate gene in 64 clinical samples and 10 ESCC cell lines (KYSE150, KYSE270, KYSE410, KYSE450, KYSE510, TE1, TE6, TE8, TE9, and TE10) using quantitative real-time PCR (qRT-PCR). [Results] In RNA-seq analysis, 34 genes showed more than 30-fold decrease in tumor samples compared to normal tissues, and the most downregulated gene was transmembrane protease serine 11B (TMPRSS11B). Amon these 34 genes, other 5 genes of TMPRSS11 family (TMPRSS11A, TMPRSS11BNL, TMPRSS11D, TMPRSS11E, and TMPRSS11F) were included. qRT-PCR analysis revealed that TMPRSS11B expression in ESCC samples were lower than those in normal samples (p < 0.001). Downregulation of TMPRSS11B in tumor samples compared to corresponding normal samples were observed in 51 cases out of 64 (79.7%). Patients with expression levels of TMPRSS11B that were below the median value were assigned to the low expression group (n = 32), whereas those with expression values above the median were assigned to the high expression group (n = 32). Significant difference was not observed between two groups regarding clinicopathological data, including age, gender, TNM stage, and lymphatic/venous invasion. TMPRSS11B expression was not detected in all of ESCC cell lines and noncancerous esophageal epithelial cell line, HET1A. [Conclusion] Our results suggest that downreguration of TMPRSS11B expression occurs in early stage of the ESCC oncogenesis and that TMPRSS11B has tumor suppressive roles in ESCC development. Citation Format: Suburu Amano, Takeshi Iwaya, Satoshi Nishizuka, Kohei Kume, Chie Ito, Yuji Akiyama, Yoshihiro Shioi, Fumitaka Endo, Akira Sasaki. Downregulation of TMPRSS11B in squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1159.