Abstract
Abstract Background: PPIB (Peptidylprolyl isomerase B) is involved in cellular transcriptional regulation, immune response, chemotaxis, and proliferation. Recent studies have shown that PPIB is linked to tumor progression and chemoresistance. The role of PPIB in non-small cell lung cancer (NSCLC) has not been explored. We aimed to investigate the significance of PPIB in NSCLC and its mechanism of action. Methods: The role of PPIB was assessed in 5 human NSCLC cell lines. PPIB expression was examined using RNA in situ hybridization (RNA-ISH) on tissue microarrays consisting of 544 NSCLC cases and Ki-67 expression was evaluated by immunohistochemical assays (IHC). RNA-ISH and IHC scores were evaluated by digital image analysis and used to compare patients' prognostic outcomes. Results: PPIB overexpression promoted proliferation, colony formation and migration of NSCLC tumor cells. We also confirmed the oncogenic properties of PPIB expression in PPIB transfected human bronchogenic epithelial cells. In NSCLC tumor samples, high PPIB expression correlated with lymph node metastasis and recurrence (p = 0.018 and 0.026, respectively), while Ki-67 overexpression correlated with advanced tumor stage (p < 0.001). Patients with high PPIB expression assessed by RNA-ISH (PPIBhigh), exhibited significantly shorter disease-free survival (DFS) time than those who were PPIBlow [HR (95% CI) = 1.53 (1.11-2.10), p = 0.008]. Multivariate analysis revealed that combined Ki-67high/PPIBhigh expression was an independent predictor of shorter DFS [HR (95% CI) = 1.71 (1.26-2.31), p < 0.001]. Conclusions: These findings suggest that PPIB plays a role in NSCLC tumor growth and is associated with unfavorable disease-free survival. PPIB may have value as a prognostic marker and a potential target molecule for NSCLC treatment. Citation Format: Jeongwon Kim, Joon-Yong Chung, Stephen M. Hewitt, Ilseon Hwang, Joon Seon Song, Chang-Min Choi, Eunho Cho, Kwon-Ho Song, Tae Woo Kim, Kris Ylaya. PPIB expression associates with tumor progression and unfavorable disease-free survival of non-small cell lung cancer [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 4311.
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