Expression of FGFR1 and EFGR in triple negative breast cancer and analyzing their interaction

  • 羅 竹君

Student thesis: Doctoral Thesis

Abstract

Prevalence of triple negative breast cancer (TNBC) is around 15% in Taiwan and the treatment presents a major clinical challenge owing to heterogeneity of cancer genome Currently chemotherapy is the mainstay of treatment of TNBC patients due to lack of common target Searching new therapeutic target is an important issue for TNBC patients In the previous studies overexpression of epidermal growth factor receptor (EGFR) is detected in approximately 70% of TNBC populations and indicated as a negative prognostic factor However the response of single use of EGFR monoclonal antibody (Cetuximab) did not achieve a better outcome comparing to combination of cetuximab and cisplatin in phase II clinical trial This result suggests that most patients have alternate mechanisms other than EGFR pathway Overexpression of fibroblast growth factor receptor 1 (FGFR1) which is also a transmembrane protein has also been proposed as a poor prognostic factor for breast cancer in recent clinical studies Therefore we tried to investigate the expression and interaction of EGFR and FGFR1 in triple negative breast cancer in Taiwan population First we tested the immunohistochemical staining with monoclonal antibody to examine the expression of targeted protein in triple-negative breast cancer We analyzed the clinicopathological and survival information based on the immunoscoring There was strong correlation between the overexpression of EGFR and poor prognosis of the patients; however the relationship between clinical prognosis of the patients and expression of FGFR1 was weak After further analysis FGFR1 overexpression was correlated with poor prognosis in low EGFR expression groups We presumed that the relationship between the EGFR and FGFR1 in the regulation of tumor growth was not co-occurrence In addition analyzing the mRNA expression and copy number alteration (CNA) of these two genes also showed the same trend in the public database (PrognoScan & cBioPortal) According to our study overexpression of EGFR was correlated to poor outcome in TNBC populations In patients with low EGFR expression FGFR1 overexpression predicted poor prognosis FGFR1 might participate in the regulation pathway of TNBC in the absence of EGFR activation
Date of Award2019
Original languageEnglish
SupervisorHui-Ping Hsu (Supervisor)

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