LAUSR

Background: Lung cancer is the leading cause of cancer death worldwide. Tumor recurrence is the most common cause of treatment failure after surgical resection. Quaking (QKI) is a functional protein that mediate alternative splicing, which belongs to the STAR family of the KH domain, containing RNA binding proteins. QKI regulate various genes via alternative splicing and circRNA formation during epithelial-mesenchymal transition (EMT). QKI takes an important part in tumorigenesis. QKI has been reported to be associated with progression of human cancer. However, several studies have indicated that QKI was associated with repression of EMT. Furthermore, the prognostic value of QKI in lung cancer patients and its regulatory mechanisms in EMT in lung cancer cells remains unknown. Materials and Methods: A total of 79 patients with resected lung adenocarcinoma were included in the study. QKI expression was determined by immunohistochemistry in tumor specimens. The prognostic value of QKI overexpression and its relationship with clinicopathological variables were investigated. QKI knockdown was performed in H1299 and A549 cells. Western blotting analysis was performed to demonstrated QKI, E-cadherin and vimentin expression. Results: QKI overexpression was significantly associated with female gender (P = 0.045). There was no significant association between QKI overexpression and predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.180). Univariate analysis indicated that predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (P = 0.006) was a significant prognostic factor for worse recurrence-free survival (RFS). QKI overexpression (P = 0.042) was a significant prognostic factor for better RFS. Increased vimentin expression and decreased E-cadherin expression were identified in H1299 and A549 cells after QKI knockdown. Conclusions: QKI overexpression has the potential to be a significant prognostic factor for better RFS in patients with resected lung adenocarcinoma. Increased vimentin expression and decreased E-cadherin expression were identified in H1299-QKIi cells. QKI may possess the ability to inhibit invasion and migration through repressing EMT. Citation Format: Ying-Shiun Kao, Jung-Jyh Hung. Quaking overexpression downregulates epithelial-mesenchymal transition in lung cancer cells [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 1224.