|Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR|
|Wang, Fen; Wang, Shuhang; Wang, Zhijie; Duan, Jianchun; An, Tongtong; Zhao, Jun; Bai, Hua; Wang, Jie|
|关键词||EGFR phosphorylation EGFR mutation Non-small cell lung cancer|
|刊名||JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH|
|WOS标题词||Science & Technology|
|关键词[WOS]||GROWTH-FACTOR RECEPTOR ; CELL LUNG-CANCER ; TYROSINE KINASE DOMAIN ; PULMONARY ADENOCARCINOMA ; MOLECULAR PREDICTORS ; ACTIVATING MUTATIONS ; POOR-PROGNOSIS ; ERBB RECEPTORS ; TUMOR RESPONSE ; GEFITINIB|
Background: EGFR mutation is a strong predictive factor of EGFR-TKIs therapy. However, at least 10% of patients with EGFR wild-type are responsive to TKIs, suggesting that other determinants of outcome besides EGFR mutation might exist. We hypothesized that activation of phosphorylated EGFR could be a potential predictive biomarker to EGFR-TKIs treatment among patients in wild-type EGFR.
Method: Total of 205 stage IIIb and IV NSCLC patients, tissue samples of whom were available for molecular analysis, were enrolled in this study. The phosphorylation of EGFR at tyrosine 1068 (pTyr1068) and 1173 (pTyr1173) were assessed by immunohistochemistry, and EGFR mutations were detected by denaturing high performance liquid chromatograph (DHPLC).
Results: Among 205 patients assessable for EGFR mutation and phosphorylation analysis, 92 (44.9%) were EGFR mutant and 165 patients (57.6%) had pTyr1173 expression. Superior progression-free survival (PFS) was seen after EGFR-TKIs therapy in patients with pTyr1068 expression compared to pTyr1068 negative ones (median PFS 7.0 months vs. 1.2 months, P < 0.001). Inversely, patients with pTyr1173 had a shorter PFS (4.8 months VS. 7.7 months, P = 0.016). In subgroup of patients with wild-type EGFR, pTyr1068 expression positive ones had a significantly prolonged PFS (4.2 months vs. 1.2 months P < 0.001) compared with those without pTyr1068 expression. Sixteen patients with both wild-type EGFR and pTyr1068 who responded to EGFR-TKIs had median PFS of 15.6 months (95% CI: 7.28-23.9).
Conclusion: pTyr1068 may be a predictive biomarker for screening the population for clinical response to EGFR-TKIs treatment; especially for patients with wild-type EGFR.
|资助机构||China National Funds for Distinguished Young Scientists ; Capital Development Foundation|
|作者单位||Peking Univ, Dept Thorac Med Oncol, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100036, Peoples R China|
|Wang, Fen,Wang, Shuhang,Wang, Zhijie,et al. Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2012,31.|
|APA||Wang, Fen.,Wang, Shuhang.,Wang, Zhijie.,Duan, Jianchun.,An, Tongtong.,...&Wang, Jie.(2012).Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,31.|
|MLA||Wang, Fen,et al."Phosphorylated EGFR expression may predict outcome of EGFR-TKIs therapy for the advanced NSCLC patients with wild-type EGFR".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 31(2012).|