Pretreatment levels of the serum biomarkers CEA, CYFRA 21–1, SCC and the soluble EGFR and its ligands EGF, TGF-alpha, HB-EGF in the prediction of outcome in erlotinib treated non-small-cell lung cancer patients

Abstract

The aim of this study has been to investigate the potential of serum biomarkers used in clinical practice (CEA, CYFRA 21–1, SCC) together with the serum epidermal growth factor receptor (EGFR) and its associated ligands (EGF, TGF-α, HB-EGF) as outcome predictors of non-small cell lung cancer (NSCLC) patients treated with the TKI erlotinib. The pretreatment levels of these markers were evaluated through immunoassays carried out in 58 patients. The progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan-Meier method and differences between groups were compared by means of the Log-Rank test. Association of risk factors with survival was evaluated using the univariate and multivariate Cox modelling procedures. Higher CEA (>5 ng/mL) and sEGFR (>56.87 ng/mL) concentrations associated significantly with a higher overall survival. The pre-treatment sEGFR serum levels constituted an independent prognostic factor. The EGFR gene mutational status and the sEGFR level combination was the single to associate significantly with longer progression-free survival periods, in circumstances in which the EGFR gene was mutated and increased protein serum levels were detected. The overall survival as assessed through a Cox analysis revealed similar death hazards with respect to low sEGFR levels combined both with non-mutated EGFR genotypes and low CEA serum levels. Our results suggest that the pre-treatment CEA and sEGFR serum levels may provide a comparable source of information to that supplied by the EGFR gene mutational status with respect to the prognosis of erlotinib treated NSCLC patients. A combined sEGFR and CEA level appraisal could be of considerable value to select patients to undergo EGFR-TKI treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-0891-0) contains supplementary material, which is available to authorized users.

Three Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting NSCLC

“…In addition, the diagnostic performance of the combination panel of these three lncRNA (AUC, 0.942) was significantly higher than that of CEA [13,14].…”

Interaction of cytokeratin 19 head domain and HER2 in the cytoplasm leads to activation of HER2-Erk pathway

“…The major cellular functions of cytokeratins are mechanical support, cytoarchitecture, cell migration, and signal modulation26. Among keratins, the KRT19 is the smallest member of the type I keratin family and is known as a tumor marker in several kinds of malignancies12131415161718. Regarding the function of KRT19 in cancers, the expression of KRT19 might contribute to the invasiveness of hepatocellular carcinoma (HCC)27.…”

“…In the course of identifying novel partner receptor for TD mutant HER2, we found that cytokeratin 19 (KRT19) is bind to wild type HER2 in A549 lung cancer cell line. KRT19, which is a member of the keratin intermediate filament family of proteins, is well known to be generally overexpressed in various cancers121314151617, and its fragment known as CYFRA has been shown to be a tumor marker in some subsets of lung cancers1218. In this study, we determined the binding sites of KRT19 and HER2 and investigated the impact of KRT19 and HER2 interactions in signal transduction pathways to decode their possible roles in oncogenesis.…”

Factors associated with efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer

“…Another study demonstrated that pretreatment higher CEA (>5 ng/mL) was significantly associated with a higher OS as compared to the normal levels in patients receiving erlotinib. 64 The reason maybe that lung adenocarcinoma patients with high serum CEA levels are more likely to harbor EGFR-sensitive mutations 65,66 according to the study conducted in an unselected NSCLC population and a majority were lung adenocarcinoma patients. 64 A similar conclusion was obtained in another study; however, the cutoff value for CEA levels was 20 ng/ mL.…”