Abstract 7269: Karyopherin α-2, a nuclear export protein, promotes cancer progression in lung adenocarcinoma

Abstract Introduction: Karyopherin α-2 (KPNA2), a nucleocytoplasmic transport protein, regulates the nuclear import of macromolecules and contributes to carcinogenesis. Actually, KPNA2 is upregulated in various types of cancer tissues and serum from cancer patients. In particular, it is associated with cancer invasiveness and poor prognosis in patient. Here, we tried to present the molecular mechanism and clinical significance of KPNA2 in lung cancer progression and metastasis. Method: First, we retrospectively analyzed the data extracted from EMR for patients with non-small cell lung cancer receiving curative surgical resection in Uijeongbu and Bucheon St. Mary’s Hospitals (n=165). Immunohistochemistry staining was performed on the tumor microarray samples using antibodies against KPNA2. The functional assay and gene silencing was conducted. Result: The clinical and pathological information of the experimental group is as follows. Based on the TMA staining, mean KPNA2 score was 36.5 [0-240] and median value was 10. Based on the TMA staining, patients with high KPNA2 expression were related to lymphatic invasion (p = 0.00782), advanced stage (p = 0.0202), and current smoker (p = 0.0074). KPNA2 expression was higher in squamous cell carcinoma than in adenocarcinoma histotype. Patients with high KPNA2 expression showed shorter survival than those with low KPNA2 (median OS (months), 72.8 vs 42.2, P < 0.0001; median RFS (months), 72.8 vs 32.1, P < 0.0011) and relevant to high recurrence (recurrence rate (%), 24.7 vs 44.7, p = 0.007). Further, high KPNA2 expression was associated with poor survival outcomes. Knockdown of KPNA2 in lung cancer cells suppressed the invasion and migration of lung cancer cells and inhibited metastasis in a mouse model of lung cancer. Inversely, KPNA2 overexpression promoted cancer cell growth, invasion, and migration. Moreover, ectopic expression of KPNA2 made lung cancer cells less sensitive to anticancer drugs, Talazoparib and Olaparib, indicating that KPNA2 enhances drug resistance in lung cancer cells. Conclusion: Collectively, this study suggest that KPNA2 promotes invasiveness and metastasis and is associated with poor patient outcomes; therefore, KPNA2 will be a good therapeutic target or a biomarker in lung adenocarcinoma. Citation Format: Inyoung Cheon, Seoree Kim, Sengran Cho, Heejin Lee, Jung-Sook Yoon, Ji Hyun Lee, Sang Hoon Chun, Hye Sung Won, Soon Auck Hong, Yoon Ho Ko, Young-Ho Ahn. Karyopherin α-2, a nuclear export protein, promotes cancer progression in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7269.