Correlation of EGFR Del 19 with Fn14/JAK/STAT signaling molecules in non-small cell lung cancer

Sun,Ying; Han,Yong; Wang,Xiaoping; Wang,Wuping; Wang,Xuejiao; Wen,Miaomiao; Xia,Jinghua; Xing,Hao; Li,Xiaofei; Zhang,Zhipei

doi:10.3892/or.2016.4905

Correlation of EGFR Del 19 with Fn14/JAK/STAT signaling molecules in non-small cell lung cancer

Authors:
- Ying Sun
- Yong Han
- Xiaoping Wang
- Wuping Wang
- Xuejiao Wang
- Miaomiao Wen
- Jinghua Xia
- Hao Xing
- Xiaofei Li
- Zhipei Zhang
View Affiliations

Affiliations: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: June 23, 2016 https://doi.org/10.3892/or.2016.4905
Pages: 1030-1040

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Abstract

Previous research has shown that p-EGFR (particularly mutated EGFR) may activate fibroblast growth factor-inducible 14 (Fn14) expression in non-small cell lung cancer (NSCLC), and the JAK/STAT signaling pathway may participate in this process. Thus, in order to verify this hypothesis, correlations among the expression levels of EGFR Del 19, Fn14 and JAK/STAT were detected and analyzed. The expression and location of these molecules were assessed using IHC, immunohistofluorescence, RT-qPCR and western blotting. The differences and correlations in the expression of these molecules and clinical pathological characteristics were statistically analyzed using Mann-Whitney U, Kruskal‑Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of EGFR Del 19 and Fn14 expression on survival. Data showed that EGFR Del 19, Fn14 and JAK1/STAT1 expression was significantly related with differentiation, pTNM stage and lymphatic metastasis (P<0.01) and there was a marked correlation of EGFR Del 19, Fn14 and JAK1/STAT1 expression with histological type, differentiation, pTNM stage of NSCLC (P<0.05; rs>0.3). Immunohistofluorescence showed that there was a co-localization phenomenon between EGFR Del 19 and Fn14 expression. NSCLC patients with higher EGFR Del 19/Fn14 expression had a significantly worse prognosis than those with lower EGFR Del 19/Fn14 expression (P=0.0155/P=0.001; log-rank test). The multivariate analysis indicated that Fn14 expression may be an independent prognostic factor in NSCLC with EGFR Del 19 [hazard ratio (HR), 0.326; P=0.042]. Therefore, our results indicate that EGFR Del 19 may promote Fn14 and JAK1/STAT1 expression in NSCLC and Fn14 may serve as a prognostic biomarker in NSCLC with EGFR Del 19.

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