Cytoplasmic, but not nuclear Nrf2 expression, is associated with inferior survival and relapse rate and response to platinum-based chemotherapy in non-small cell lung cancer

doi:10.1111/1759-7714.13479

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Title:	Cytoplasmic, but not nuclear Nrf2 expression, is associated with inferior survival and relapse rate and response to platinum-based chemotherapy in non-small cell lung cancer
Authors:	Chen, Ming-Jenn Lin, Po-Lin Wang, Lee Cheng, Ya-Min Chen, Chih-Yi Lee, Huei
Contributors:	Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Dept Sports Management, Coll Leisure & Recreat Management Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery Chung Shan Med Univ, Dept Publ Hlth Natl Cheng Kung Univ, Dept Obstet & Gynecol, Coll Med Chung Shan Med Univ Hosp, Dept Surg
Keywords:	NSCLC chemotherapeutic response cytoplasmic Nrf2 prognosis
Date:	2020
Issue Date:	2022-11-18 11:25:00 (UTC+8)
Publisher:	Wiley
Abstract:	Background Several studies have previously indicated that nuclear factor erythroid 2-related factor 2 (Nrf2) expression may promote tumor progression when the Keap1/Nrf2 pathway is activated, but few reports have demonstrated the role of cytoplasmic Nrf2 on tumorigenesis. Methods Immunohistochemistry was conducted to evaluate Nrf2 expression in 167 tumors from surgically-resected patients with non-small cell lung cancer (NSCLC). Univariate and multivariate analyses were performed to examine the association of Nrf2 expression with patients' prognosis. This study was conducted to examine the association of Nrf2 expression with tumor response to cisplatin-based chemotherapy. Results Among these tumors, 56 and 32 of 167 tumors expressed Nrf2 in the cytoplasm (34% for C+/N-) and in the cytoplasm/nucleus (19% for C+/N+), but not in the nucleus of tumor cells. Nrf2 was negatively expressed in the remainder of the tumor samples (C-/N-, 79 of 167, 47%). Univariate analysis indicated that patients with Nrf2 positive tumors (C+/N- plus C+/N+) had worse overall survival (OS), but not relapse-free survival (RFS) than with Nrf2 negative tumors (C-/N-). However, patients with C+/N- tumors possessed worse OS and RFS than those with Nrf2 negative tumors (C-/N-). Multivariate analysis further confirmed the prognostic significance of patients with Nrf2 positive and C+/N- tumors on OS and RFS, but not on RFS for patients with Nrf2 positive tumors. Patients with Nrf2 positive and C+/N- tumors were determined to more frequently have an unfavorable response to cisplatin-based chemotherapy than those with Nrf2 negative tumors. Conclusions Cytoplasmic Nrf2 expression might potentially be used to predict poor prognosis and unfavorable response to cisplatin-based chemotherapy in patients with NSCLC.
Relation:	Thoracic Cancer, v.11, n.7, pp.7
Appears in Collections:	[Dept. of Sports Management] Periodical Articles

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