Abstract 4829: The clinical significance of APOBEC3B in esophageal squamous cell carcinoma
Authors: Keisuke Kosumi, Yoshifumi Baba, Takatsugu Ishimoto, Kenichi Nakamura, Kazuto Harada, Mayuko Ohuchi, Yuki Kiyozumi, Daisuke Izumi, Ryuma Tokunaga, Junji Kurashige, Ryuichi Karashima, Yukiharu Hiyoshi, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
Journal: Cancer Research (2015)

Abstract Backgrounds: APOBEC3B is one of the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family, and APOBEC3B can induce transitions into target DNA through cytidine deamination. To date, APOBEC attracts attention due to its functioning as part of the innate immune system by protecting against retrovirus and retrotransposon propagation. And, recent studies revealed that APOBEC3B might contribute to several mutations in various types of cancers, including cervical, breast, head and neck, lung, bladder cancers, and APOBEC3B may have a crucial role in carcinogenesis and cancer development. Esophageal squamous cell carcinoma (ESCC) reportedly has several molecular features, and we recently reported that long interspersed nucleotide element 1 (LINE-1) hypomethylation might contribute to poor prognosis and PIK3CA mutation to good prognosis in ESCC. However, there is no report which investigates the relationship between APOBEC3B expression, clinical and pathological features in ESCC. Methods: We compared the expression of APOBEC3B mRNA between cancer tissues and noncancerous esophageal mucosae by using GEO profiles and ESCC frozen tissues. In addition, we investigated the relationships between the APOBEC3B immunohistochemical expression levels, clinical and pathological features, and molecular features including p53 expression, global DNA methylation level and PIK3CA mutation. We quantified LINE-1 retrotransposons, of which a substantial portion of the human genome consists, to assess global DNA methylation. Results: APOBEC3B expression at mRNA level was significantly higher in cancer tissues than in noncancerous esophageal mucosae (P = 0.050). In the immunohistochemical study, the APOBEC3B expression of ESCC was stronger than that of noncancerous esophageal mucosa. We found no significant correlation of APOBEC3B expression with tumor size, T stage, N stage and pStage (P = 0.74, P = 0.32, P = 0.19, P = 0.23, respectively). There were no correlation between APOBEC3B expression and prognosis. There was no correlation between APOBEC3B expression and p53 expression (P = 0.23), but, interestingly, a high expression of APOBEC3B was significantly associated with LINE-1 hypomethyaltion and PIK3CA mutation (P = 0.029, P = 0.020). Conclusions: APOBEC3B high expression had significant relationships with LINE-1 hypomethylation and PIK3CA mutation, supporting that APOBEC3B might contribute to malignant behavior through the molecular features in ESCC. Citation Format: Keisuke Kosumi, Yoshifumi Baba, Takatsugu Ishimoto, Kenichi Nakamura, Kazuto Harada, Mayuko Ohuchi, Yuki Kiyozumi, Daisuke Izumi, Ryuma Tokunaga, Junji Kurashige, Ryuichi Karashima, Yukiharu Hiyoshi, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba. The clinical significance of APOBEC3B in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4829. doi:10.1158/1538-7445.AM2015-4829