Association of Sarcopenia with a Poor Prognosis and Decreased Tumor-Infiltrating CD8-Positive T Cells in Pancreatic Ductal Adenocarcinoma: A Retrospective Analysis
Shigeto Masuda, Kohei Yamakawa, Atsuhiro Masuda, Hirochika Toyama, Keitaro Sofue, Yoshihide Nanno, Shohei Komatsu, Satoshi Omiya, Arata Sakai, Takashi Kobayashi, Takeshi Tanaka, Masahiro Tsujimae, Shigeto Ashina, Masanori Gonda, Shohei Abe, Hisahiro Uemura, Shinya Kohashi, Noriko Inomata, Kae Nagao, Yoshiyuki Harada, Mika Miki, Yosuke Irie, Noriko Juri, Maki Kanzawa, Tomoo Itoh, Takumi Fukumoto, Yuzo Kodama
Abstract
Abstract Background Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30–65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment. Patients and Methods We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration ( KRAS , TP53 , CDKN2A /p16, and SMAD4 ) and tumor immune (CD4 + , CD8 + , and FOXP3 + ) and fibrosis status (stromal collagen). Results In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8 + T cells in the sarcopenia group were significantly less than in the non-sarcopenia group ( P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb). Conclusions Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8 + T cells in localized-stage PDAC. Sarcopenia may worsen a patient’s prognosis by suppressing local tumor immunity.