Open Access

Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion

  • Authors:
    • Haihong Yang
    • Fengnan Wang
    • Qiuhua Deng
    • Dakai Xiao
    • Ping He
    • Xiaodong Lin
    • Dongyun He
  • View Affiliations

  • Published online on: January 25, 2019     https://doi.org/10.3892/ol.2019.9972
  • Pages: 3071-3076
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Secondary KIT gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion‑positive advanced non‑small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c‑Kit) or platelet‑derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c‑Kit (p‑c‑Kit) and phosphorylated PDGFRA (p‑PDGFRA) and the prognosis of ALK fusion NSCLC was investigated. Advanced stage NSCLC samples with ALK fusion were tested for their p‑c‑Kit and p‑PDGFRA content by immunohistochemical staining, and for its association with crizotinib efficacy and the survival of the patients. Of 64 eligible ALK‑positive patients with NSCLC, 30 (46.9%) were p‑c‑Kit‑positive and 10 (15.7%) were p‑PDGFRA‑positive. Brain metastases were more common in ALK‑positive cases that were p‑PDGFRA‑positive compared with those who were p‑PDGFRA‑negative. ALK‑positive patients treated with crizotinib, who exhibited high levels of p‑c‑Kit had significantly lower progression‑free survival times than those with low levels. In addition, the patients with high levels of p‑c‑Kit exhibited lower overall survival times than those with low levels. Furthermore, multivariate analysis indicated that high levels of p‑c‑Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time. However, no statistically significant difference was observed in the survival of patients with different p‑PDGFRA levels. p‑PDGFRA was more frequently expressed in the ALK‑positive cases with brain metastasis. c‑Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC.
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March-2019
Volume 17 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yang H, Wang F, Deng Q, Xiao D, He P, Lin X and He D: Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion. Oncol Lett 17: 3071-3076, 2019
APA
Yang, H., Wang, F., Deng, Q., Xiao, D., He, P., Lin, X., & He, D. (2019). Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion. Oncology Letters, 17, 3071-3076. https://doi.org/10.3892/ol.2019.9972
MLA
Yang, H., Wang, F., Deng, Q., Xiao, D., He, P., Lin, X., He, D."Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion". Oncology Letters 17.3 (2019): 3071-3076.
Chicago
Yang, H., Wang, F., Deng, Q., Xiao, D., He, P., Lin, X., He, D."Predictive and prognostic value of phosphorylated c‑KIT and PDGFRA in advanced non‑small cell lung cancer harboring ALK fusion". Oncology Letters 17, no. 3 (2019): 3071-3076. https://doi.org/10.3892/ol.2019.9972