Abstract 1770: The association between sarcopenia and cellular senescence of cancer associated fibroblast in pancreatic cancer

Abstract

Abstract Background: Sarcopenia is a syndrome that is characterized by progressive and generalized loss of skeletal muscle mass and strength. Several recent studies have shown that sarcopenia has prognostic significance for patients with malignant disease, including cancers of the esophagus, colon, pancreas and liver. On the other hand, cellular senescence is gaining increased attention from clinicians and researchers, yet incompletely understood role in the development of malignant disease. Previous studies reported that Caveolin-1 expression in cancer associated fibroblast is associated with cancer progression, and it is known in recent years that caveolin-1 plays a major role in controlling cellular senescence. Therefore, we hypothesized that sarcopenia causes cellular senescence of cancer associated fibroblast (CAF). The aim of this study is to clarify the between sarcopenia and cellular senescence of CAF through Caveolin-1 in pancreatic cancer. Methods: All consecutive patients with pancreatic cancer underwent curative resection between January 2004 and December 2014 were enrolled in this retrospective study. Skeletal muscle and visceral fat amount at the third lumbar vertebra (L3) in the inferior direction were quantified using enhanced computed tomography. The patients were divided into two groups, with and without sarcopenia, based on Japan Society of Hepatology guidelines for sarcopenia. Next, Caveolin-1 expression was analyzed by immunohistochemistry (IHC). Moreover, we investigated the relationship between sarcopenia and Caveolin-1 expression. Results: Forty-one (31.5%) of 130 patients were identified with sarcopenia. Kaplan-Meier analysis showed that patients with sarcopenia had a significantly worse cancer specific survival than patients without sarcopenia (3-year-survival: 37.2% vs 50.4%, respectively, p = 0.038). While, a high level of Caveolin-1 expression was detected in 29.2% (38/130) of our samples. High Caveolin-1 expression in CAF significantly correlated with poor prognoses with respect to overall survival (log-rank p = 0.014) and disease-free survival (log-rank p = 0.0015). However, there was no relationship between sarcopenia and IHC score of Caveolin-1 expression in CAF. Conclusion: The present result suggested that sarcopenia and Caveolin-1 expression of CAF in patient with pancreatic cancer is respectively associated with poor prognosis, but not associated each other. Now, we focus on Caveolin-1 expression of CAF, and establish primary cultures of CAF from the pancreatic cancer tissues and examine its function. Citation Format: Kensuke Yamamura, Yo-ichi Yamashita, Yuki Kitano, Kota Arima, Takayoshi Kaida, Tatsunori Miyata, Shigeki Nakagawa, Kosuke Mima, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Hideo Baba. The association between sarcopenia and cellular senescence of cancer associated fibroblast in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1770. doi:10.1158/1538-7445.AM2017-1770