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Association of cytoplasmic p27 expression with an unfavorable response to cisplatin-based chemotherapy and poor outcomes in non-small cell lung cancer

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Tumor Biology

Abstract

Reduced nuclear p27 expression is associated with a poor outcome in various cancers, including non-small cell lung cancer (NSCLC). Cytoplasmic p27 expression was shown to be associated with an unfavorable response to chemotherapy and poor outcomes in some carcinomas, but it has not been well studied in NSCLC. Herein, p27 expression in 219 tumors surgically resected from NSCLC patients was evaluated by immunohistochemistry (IHC). The most common of p27 immunostaining in lung tumors was observed in the cytoplasm (N−/C+, 32 %), followed by negative (N−/C−, 29 %), nucleus (N+/C−, 24 %), and nucleus plus cytoplasm (N+/C+, 15 %). Kaplan–Meier and Cox regression models showed that p27 N−/C+ tumors exhibited the worst overall survival (OS) and relapse-free survival (RFS) among the four categories of tumors. Among 135 of 219 patients who received cisplatin-based chemotherapy, p27 N−/C+ tumors most commonly showed an unfavorable response to cisplatin-based chemotherapy, followed by p27 N−/C− tumors when p27 N+/C− tumors were used as a reference. IHC analysis for phosphorylated extracellular signal-regulated kinase (p-ERK) and Bcl-2 expression in the lung tumors was performed to test whether ERK activation could enhance p27 nuclear export and the expression of Bcl-2 to test whether ERK activation could enhance p27 nuclear export and Bcl-2 expression. The data showed that p-ERK expression was positively correlated with cytoplasmic p27 (N−/C+) and Bcl-2 expression in the lung tumors. Patients with high Bcl-2-expressing tumors treated with cisplatin-based chemotherapy showed unfavorable predictive values in a subset of this study population. Therefore, we suggest that cytoplasmic p27 (N−/C+) via ERK-activated Bcl-2 expression may predict an unfavorable response to cisplatin-based chemotherapy and poor outcomes in NSCLC.

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Acknowledgments

This work was jointly supported by grants from the National Health Research Institute (NHRI-EX103-10328BI) and the Ministry of Science and Technology (MOST103-2320-B-038-036-MY2) Taiwan.

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    Authors and Affiliations

    1. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, China

      Tsang-Chi Lin & Lung-Hung Tsai

    2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, China

      Tsang-Chi Lin, Lung-Hung Tsai, Ming-Chih Chou & Chih-Yi Chen

    3. Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Room 5, 12th floor, No. 3, Park Street, Nangang District, 115, Taipei City, Taiwan, China

      Huei Lee

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    1. Tsang-Chi Lin
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    Correspondence to Huei Lee.

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    The IRB approval was accepted by the hospital’s institutional review board (Institutional Review Board, Chung Shan Medical University Hospital; No. CS07115).

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    Tsang-Chi Lin and Lung-Hung Tsai contributed equally to this work.

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    Lin, TC., Tsai, LH., Chou, MC. et al. Association of cytoplasmic p27 expression with an unfavorable response to cisplatin-based chemotherapy and poor outcomes in non-small cell lung cancer. Tumor Biol. 37, 4017–4023 (2016). https://doi.org/10.1007/s13277-015-4272-7

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    • DOI: https://doi.org/10.1007/s13277-015-4272-7

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