RESEARCH ARTICLE
High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy Guang Yang☯, Xue-Jiao Wang☯, Li-Jun Huang☯, Yong-An Zhou, Feng Tian, Jin-Bo Zhao, Peng Chen, Bo-Ya Liu, Miao-Miao Wen, Xiao-Fei Li*, Zhi-Pei Zhang* Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi’an, 710038, China ☯ These authors contributed equally to this work. * [email protected] (XFL); [email protected] (ZPZ)
Abstract OPEN ACCESS Citation: Yang G, Wang X-J, Huang L-J, Zhou Y-A, Tian F, Zhao J-B, et al. (2015) High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy. PLoS ONE 10(8): e0135576. doi:10.1371/journal.pone.0135576 Editor: Gergely Szakacs, Hungarian Academy of Sciences, HUNGARY Received: October 29, 2014 Accepted: July 23, 2015 Published: August 13, 2015 Copyright: © 2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ATP-binding cassette (ABC) transporters are associated with poor response to chemotherapy, and confer a poor prognosis in various malignancies. However, the association between the expression of the ABC sub-family G member 4 (ABCG4) and prognosis in patients with non-small-cell lung cancer (NSCLC) remains unclear. NSCLC tissue samples (n = 140) and normal lung tissue samples (n = 90) were resected from patients with stage II to IV NSCLC between May 2004 and May 2009. ABCG4 mRNA and protein expressions were detected by RT-PCR, western blot, and immunohistochemistry. Patients received four cycles of cisplatin-based post-surgery chemotherapy and were followed up until May 31st, 2014. ABCG4 positivity rate was higher in NSCLC than in normal lung tissues (48.6% vs. 0%, P75%: 4); b) the staining intensity (no color: 0; yellow: 1; brown: 2; and tan: 3); and c) the two grades were multiplied together and specimens were assigned to one of 4 levels: 0: negative (-); 1–4: weakly positive (+); 5–8: moderately positive (++); 9–12: strongly positive (+++) [34]. For multivariate analysis and comparison with the survival curves,–was defined as negative, and +, ++ and +++ were all defined as positive.
Statistical analysis Statistical analyses were performed using SPSS 18.0 (IBM, Armonk, NY, USA). Associations between immunohistochemical expression and clinical variables were evaluated by Mann-Whitney U or Kruskal-Wallis H test, as appropriate. Overall survival was measured from the start of chemotherapy to the date of death from any cause or the date the patient was last deemed to be alive. Survival curves were estimated by the Kaplan-Meier method, and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Correlations were assessed using the Spearman rank correlation analysis. The rank correlation coefficients were expressed as rs. 0.0rs
High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy Guang Yang☯, Xue-Jiao Wang☯, Li-Jun Huang☯, Yong-An Zhou, Feng Tian, Jin-Bo Zhao, Peng Chen, Bo-Ya Liu, Miao-Miao Wen, Xiao-Fei Li*, Zhi-Pei Zhang* Department of Thoracic Surgery, Tangdu Hospital, the Fourth Military Medical University, Xi’an, 710038, China ☯ These authors contributed equally to this work. * [email protected] (XFL); [email protected] (ZPZ)
Abstract OPEN ACCESS Citation: Yang G, Wang X-J, Huang L-J, Zhou Y-A, Tian F, Zhao J-B, et al. (2015) High ABCG4 Expression Is Associated with Poor Prognosis in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin-Based Chemotherapy. PLoS ONE 10(8): e0135576. doi:10.1371/journal.pone.0135576 Editor: Gergely Szakacs, Hungarian Academy of Sciences, HUNGARY Received: October 29, 2014 Accepted: July 23, 2015 Published: August 13, 2015 Copyright: © 2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ATP-binding cassette (ABC) transporters are associated with poor response to chemotherapy, and confer a poor prognosis in various malignancies. However, the association between the expression of the ABC sub-family G member 4 (ABCG4) and prognosis in patients with non-small-cell lung cancer (NSCLC) remains unclear. NSCLC tissue samples (n = 140) and normal lung tissue samples (n = 90) were resected from patients with stage II to IV NSCLC between May 2004 and May 2009. ABCG4 mRNA and protein expressions were detected by RT-PCR, western blot, and immunohistochemistry. Patients received four cycles of cisplatin-based post-surgery chemotherapy and were followed up until May 31st, 2014. ABCG4 positivity rate was higher in NSCLC than in normal lung tissues (48.6% vs. 0%, P75%: 4); b) the staining intensity (no color: 0; yellow: 1; brown: 2; and tan: 3); and c) the two grades were multiplied together and specimens were assigned to one of 4 levels: 0: negative (-); 1–4: weakly positive (+); 5–8: moderately positive (++); 9–12: strongly positive (+++) [34]. For multivariate analysis and comparison with the survival curves,–was defined as negative, and +, ++ and +++ were all defined as positive.
Statistical analysis Statistical analyses were performed using SPSS 18.0 (IBM, Armonk, NY, USA). Associations between immunohistochemical expression and clinical variables were evaluated by Mann-Whitney U or Kruskal-Wallis H test, as appropriate. Overall survival was measured from the start of chemotherapy to the date of death from any cause or the date the patient was last deemed to be alive. Survival curves were estimated by the Kaplan-Meier method, and compared using the log-rank test. The Cox proportional hazards model was used for univariate and multivariate analyses. Correlations were assessed using the Spearman rank correlation analysis. The rank correlation coefficients were expressed as rs. 0.0rs
