Abstract 5444: Clinical significance of tetraspanin CD63 in human ESCC

Abstract

Abstract Background: ESCC(Esophageal Squamous Cell Carcinoma) is highly aggressive due to its tendency to metastasize to the lymph nodes and organs. Our laboratory previously reported that the exosome amount in the peripheral blood could predict the prognosis of ESCC patients. CD63 is a tetraspanin family protein and is often used as a marker of exosome.CD63 highly express in early stage melanoma and thought to be a suppressive factor against EMT (epithelial-to-mesenchymal transition) in melanoma. On the other hand, some report confirmed CD63 as a prometastatic factor via regulating E cadherin expression. The function of CD63 are still controversial. We herein assessed CD63 expression and clinicopathological findings in ESCCpatient, and assessed molecular roles of CD63 in ESCC cell lines. Materials and methods: The relationship between the CD63 expression in the resected ESCC specimen (from 1997 to 2006, n=86) and clinicathological features were assessed using immunohistochemical staining. Human ESCC cell lines (TE2,TE15) were used as high CD63 expression cell lines for in vitro analysis. CD63 was knockdown using siRNA, and CD63 down regulate was confirmed by western blot and PCR. The influence on the cell behavior and gene expressions were assessed by cell proliferation assay, mRNA microarray, and GSEA(Gene Set Enrichment Analysis). Results: There were no statistically significant correlation between the CD63 expression and age, sex, tumor depth (T), lymph node metastasis (N), distant organ metastasis (M), differentiation of tumor, lymphatic vessel invasion (ly), venous invasion (v), the type of progression. As for the prognosis, the high CD63 expression patients have significantly poorer prognosis than the low expression of CD63 patients. (P=0.047, log rank test). In vitro study, cell proliferation assay showed down expression of CD63 reduce cell proliferation. Knock down of CD63 downregulates HER2 expression and influence on other ERBB signaling pathways. Conclusions: High CD63 expression predicts poor prognosis in human ESCC. The molecular function of CD63 could have relationship to ERBB signaling pathways in human ESCC cells. Citation Format: Yasunori Matsumoto, Masayuki Kano, Kentaro Murakami, Satoshi Endo, Takeshi Toyozumi, Tadashi Shiraishi, Toshiki Kamata, Takahiro Ryuzaki, Kazuya Kinoshita, Soichiro Hirasawa, Hisahiro Matsubara. Clinical significance of tetraspanin CD63 in human ESCC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5444.