Abstract 4620: Expression of nestin affect resistance to chemotherapy and clinical outcome in small cell lung caner
Authors: Kazuki Sone, Ken Maeno, Eiji Kunii, Osamu Takakuwa, Akira Takeuchi, Satoshi Fukuda, Takamitsu Asano, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Tetsuya Oguri, Akio Niimi
Journal: Cancer Research (2018)

Abstract Background: Small cell lung cancer (SCLC) is an aggressive and highly metastatic lung cancer subtype. Nestin is a member of the intermediate filament family and serves as a potential proliferative and multipotency marker in neural progenitor and stem cell. Aberrant expression of nestin is linked to malignant characteristics and poor prognosis in different cancers, including non-small cell lung cancer. However, in SCLC, the association between nestin expression and clinicopathological feature or prognosis has remained unclear. In this study, we examined whether the expression of nestin affect malignant feature and clinical outcome in SCLC. Material and methods: To assess the function of nestin, a short hairpin RNA (shRNA) targeting nestin and a forced expression vector of the nestin gene were transfected into SCLC cell lines (DMS53 and SKLC17). And three lung cancer cell lines (PC6, PC9 and PC14) and their cisplatin-resistant sub-lines were also analyzed. Nestin expression levels were assayed using Western blotting. Cell proliferation assay was performed using both nestin knock-down and overexpressed cell lines. Growth in vivo was assessed in SCID mice using a nestin knock-down cell line. Chemosensitivity was expressed as the drug concentration for IC50 in MTS cell proliferation assay. Then we retrospectively examined 84 SCLC patients. Correlations between immunohistochemical expression of nestin and various clinicopathological features were evaluated. Result: In nestin knock-down and overexpression cell lines, nesin expression was related to cell proliferation in vitro and vivo and resistance to anticancer drugs (cisplatin, etoposide and SN-38). Nestin expression levels of three cisplatin-resistant cells were increased than their parent cell lines. In 84 SCLC patients (16 patients were surgically resected, and 68 patietns were biopsied), 24 patients had nestin positive tumor. Nestin positive ratio tended to be higher in operated patients than biopsied patients. Nestin expression was not associated with age, sex, smoking status, disease stage and serum pro-gastrin releasing peptide (ProGRP) levels. There were no significant differences between nestin positive and negative patients for response rate (RR), progression free survival (PFS) and overall survival (OS) in 1st line chemotherapy. However, positive expression of nestin was associated with shorter PFS in 2nd line chemotherapy (median PFS; nestin positive 81 days vs negative 117 days, P=0.03). Conclusion: Nestin expression lead to resistance to chemotherapy and worse outcome in SCLC patients. Citation Format: Kazuki Sone, Ken Maeno, Eiji Kunii, Osamu Takakuwa, Akira Takeuchi, Satoshi Fukuda, Takamitsu Asano, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Tetsuya Oguri, Akio Niimi. Expression of nestin affect resistance to chemotherapy and clinical outcome in small cell lung caner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4620.