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. 2020 Jan;9(2):487-495.
doi: 10.1002/cam4.2706. Epub 2019 Nov 25.

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations

Huijuan Wang  1 , Ziqi Wang  1 , Guowei Zhang  1 , Mina Zhang  1 , Xiaojuan Zhang  1 , Haixia Li  1 , Xuanxuan Zheng  1 , Zhiyong Ma  1
Affiliations
Free PMC article

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations

Huijuan Wang et al. Cancer Med. 2020 Jan.
Free PMC article

Abstract

Background: A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC).

Methods: Data from 552 patients with advanced NSCLC treated from January 2015 to June 2017 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Next-generation sequencing was used to detect mutations in eight reported driver genes and various risk factors were evaluated.

Results: Of the 552 patients with advanced NSCLC, 153 (27.7%) had brain metastases. The univariate analysis showed that age (P = .008), gender (P = .016), smoking history (P = .010), lymph node metastasis (P = .003), and three driver genes, positive epidermal growth factor receptor (EGFR) mutation (P = .001), positive anaplastic lymphoma kinase (ALK) gene fusion (P = .021), and positive rearranged during transfection (RET) gene fusion (P = .003), were the factors influencing the incidence of brain metastasis. Logistic multivariate regression analysis revealed that positive EGFR mutation (P = .012), positive ALK gene fusion (P = .015), positive RET gene fusion (P = .003), pathological type (P = .009), lymph node N2-3 metastasis (P < .001), and a younger age (P < .001) were independent risk factors for brain metastasis. In addition, a receiver operating characteristic (ROC) curve was plotted with the above factors with an area under the curve = 0.705 (P < .001).

Conclusions: An EGFR mutation, ALK gene fusion, and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes.

Impact: An EGFR mutation, and ALK and RET gene fusions are risk factors for brain metastasis in advanced NSCLC patients.

Keywords: brain metastases; clinicopathological features; driver genes; lung cancer; non-small cell lung cancer (NSCLC); targeted therapy.

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Conflict of interest statement

The authors declare there are no potential conflicts of interest.

Figures

Figure 1
Figure 1
Distribution of 8 main driver gene mutations and double site gene mutations in 552 patients with lung cancer
Figure 2
Figure 2
Epidermal growth factor receptor (EGFR), RET, anaplastic lymphoma kinase (ALK) gene status, lymph node metastasis, age, and pathological type including multifactor receiver operating characteristic (ROC) curve
See this image and copyright information in PMC

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