Abstract 2239: Investigation of the molecular biological significance of YAP/TAZ expression in PNEN

Abstract

Abstract [Background] Neuroendocrine neoplasms (NEN) developing in the digestive organs are relatively rare tumors, with 3 to 5 new cases per 100,000 population annually, most of which occur in the pancreas and digestive tract. In pancreatic neuroendocrine neoplasms (PNEN), the risk of metastasis and progression varies depending on the grade of the tumor, even when the tumor size is small. In clinical practice, it is often difficult to determine the indication for surgery or multidisciplinary treatment with chemotherapy. The mechanisms of tumor formation and progression in PNEN remain unknown. YAP/TAZ have been known to play an important role in pancreatic development. Here, we explore the biological and clinical significance of YAP/TAZ over-expression in PNEN. [Methods] Immunostaining for YAP/TAZ was performed using 92 resected specimens in PNEN patients, and the association between YAP/TAZ overexpression and clinicopathological factors was elucidated. Furthermore, we generated a PNEN cell line with YAP and TAZ over-expression using QGP-1, and examined the intracellular signals regulated by YAP/TAZ expression. [Results and Discussion] The overexpression of YAP, TAZ, and YAP/TAZ were observed in 55, 55, and 32patients, respectively. High YAP expression was significantly associated with positive lymphovascular invasion (p=0.04). YAP/TAZ-high group displayed significantly worse Overall survival (p=0.0023) and recurrence-free survival (p=0.007) compared to those in others. By Western-blotting, YAP/TAZ overexpression in the QGP-1 cell line enhanced phosphorylation of Akt and Erk1/2. [Conclusions] High expression of YAP/TAZ in PNEN was implicated in poor prognosis, and was also associated with Akt, Erk1/2, and mTOR. Citation Format: Yuta Shiraishi, Hiromitsu Hayashi, Daisuke Ogawa, Shinsei Yumoto, Hiroki Sato, Takashi Matsumoto, Toru Takematsu, Masataka Maruno, Masayo Tsukamoto, Tatsunori Miyata, Shigeki Nakagawa, Kosuke Mima, Hidetoshi Nitta, Hideo Baba. Investigation of the molecular biological significance of YAP/TAZ expression in PNEN [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2239.