Serum Epidermal Growth Factor Receptor Research Articles

Value of Immunological Biomarkers in Early Prediction of Bacillus Calmette-Guerin Failure in High-Risk Non-muscle-invasive Bladder Cancer

Objectives To investigate the predictive value of different immunological markers on treatment outcomes after bacillus Calmette-Guerin (BCG) induction in high-risk non-muscle-invasive bladder cancer (NMIBC). Patients and Methods Patients who underwent transurethral resection of bladder tumors for NMIBC were assessed for study eligibility. Urine and blood samples were taken from patients at baseline (immediately before the first dose of induction). Urine samples were evaluated for interleukin (IL)-6, IL-8, IL-10, IL-11, and interferon- γ by solid-phase enzyme-linked immunosorbent assay (ELISA). Blood samples were evaluated for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) using quantitative reverse transcriptase-polymerase chain reaction analysis. Each marker was assessed in relation to tumor recurrence. Results Between June 2016 and December 2019, 160 patients were included. Tumor recurrence occurred in 47 (29.38%) patients over a median (IQR) follow-up of 24 (12: 49) months. Using univariate analysis, the following urinary cytokines were associated with higher recurrence: urinary IL-6, 8, 10, 11, and interferon-γ. Also, serum EGFR and HER2 were associated with higher recurrence. On multivariate Cox regression analysis, significant variables include HER2 [HR (95%CI): 2.675 (1.367-5.233), p= 0.004], and IL-11 [HR (95%CI): 0.889 (0.825-0.957), p= 0.002]. Conclusions Serum HER2 and urinary IL-11 could be applied in clinical practice to predict BCG failure in patients with high-risk NMIBC, so those patients could be offered other modalities (radical cystectomy) early with better survival. Further studies are recommended to establish their exact role.

Nanoproteomics deciphers the prognostic value of EGFR family proteins-based liquid biopsy

Monitoring tumor-associated protein status in serum can effectively track tumors and avoid time-consuming, costly, and invasive tissue biopsy. Epidermal growth factor receptor (EGFR) family proteins are often recommended in the clinical management of multiple solid tumors. However, the low-abundance of serum EGFR (sEGFR) family proteins hinders the depth-understanding of their function and tumor management. Herein, a nanoproteomics approach coupling with aptamer-modified MOFs (NMOFs-Apt) with mass spectrometry was developed for the enrichment and quantitative analysis of sEGFR family proteins. This nanoproteomics approach exhibited high sensitivity and specificity for sEGFR family protein quantification, with the limit of quantification as low as 1.00 nM. After detecting 626 patients’ sEGFR family proteins with various malignant tumors, we concluded that the levels of serum proteins had a moderate concordance with tissue counterparts. Metastatic breast cancer patients with a high level of serum human epidermal growth factor receptor 2 (sHER2) and a low level of sEGFR had a poor prognosis, and patients with a sHER2 decrease of more than 20% had longer disease-free time after receiving chemotherapy. This nanoproteomics method provided a simple and effective approach for low-abundant serum protein detection and our results clarified the potential of sHER2 and sEGFR as cancer markers.

Epidermal growth factor receptor inhibition prevents vascular calcifying extracellular vesicle biogenesis.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease, including vascular calcification, leading to higher mortality. The release of calcifying extracellular vesicles (EVs) by vascular smooth muscle cells (VSMCs) promotes ectopic mineralization of vessel walls. Caveolin-1 (CAV1), a structural protein in the plasma membrane, plays a major role in calcifying EV biogenesis in VSMCs. Epidermal growth factor receptor (EGFR) colocalizes with and influences the intracellular trafficking of CAV1. Using a diet-induced mouse model of CKD followed by a high-phosphate diet to promote vascular calcification, we assessed the potential of EGFR inhibition to prevent vascular calcification. Furthermore, we computationally analyzed 7,651 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) and Framingham cohorts to assess potential correlations between coronary artery calcium and single-nucleotide polymorphisms (SNPs) associated with elevated serum levels of EGFR. Mice with CKD developed widespread vascular calcification, associated with increased serum levels of EGFR. In both the CKD mice and human VSMC culture, EGFR inhibition significantly reduced vascular calcification by mitigating the release of CAV1-positive calcifying EVs. EGFR inhibition also increased bone mineral density in CKD mice. Individuals in the MESA and Framingham cohorts with SNPs associated with increased serum EGFR exhibit elevated coronary artery calcium. Given that EGFR inhibitors exhibit clinical safety and efficacy in other pathologies, the current data suggest that EGFR may represent an ideal target to prevent pathological vascular calcification in CKD.NEW & NOTEWORTHY Here, we investigate the potential of epidermal growth factor receptor (EGFR) inhibition to prevent vascular calcification, a leading indicator of and contributor to cardiovascular morbidity and mortality. EGFR interacts and affects the trafficking of the plasma membrane scaffolding protein caveolin-1. Previous studies reported a key role for caveolin-1 in the development of specialized extracellular vesicles that mediate vascular calcification; however, no role of EGFR has been reported. We demonstrated that EGFR inhibition modulates caveolin-1 trafficking and hinders calcifying extracellular vesicle formation, which prevents vascular calcification. Given that EGFR inhibitors are clinically approved for other indications, this may represent a novel therapeutic strategy for vascular calcification.

Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR.

Non-small cell lung cancer (NSCLC) is a malignant tumor. Serum exosomal miR-27b is related to tumor diagnosis. We explored the roles of serum exosomal miR-27b in NSCLC. NSCLC patients were assigned to NSCLC-early/terminal groups, with healthy subjects as controls. miR-27b expression was assessed using reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficiency was analyzed using the receiver operating characteristic curve. The correlation between serum exosomal miR-27b expression and tumor markers carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen (CEA), and cytokeratin 19-soluble fragment (CYFRA21-1) was analyzed using the Pearson analysis. The downstream target genes were predicted. Epidermal growth factor receptor (EGFR) level was assessed using enzyme-linked immunosorbent assay. Correlations of miR-27b expression with serum EGFR level and CA125, CEA, and CYFRA21-1 levels were analyzed using the Pearson analysis. Serum exosomal miR-27b was diminished in NSCLC and was further decreased in the NSCLS-terminal group. The sensitivity of miR-27b < 0.8150 for NSCLC diagnosis was 76.64%, and the specificity was 83.33%. Serum exosomal miR-27b was negatively correlated with CA125, CEA, and CYFRA21-1. miR-27b targeted EGFR. Serum EGFR was raised in NSCLC and was further elevated in the NSCLS-terminal group. miR-27b expression was negatively correlated with EGFR level. EGFR level was positively correlated with CA125, CEA, and CYFRA21-1 levels. Collectively, low expression of miR-27b assisted NSCLC diagnosis, and miR-27b exerted effects on NSCLC through EGFR.

Influence of Serum TGF-β1 and EGFR Levels on the Therapeutic Effect of High-Dose AraC in Patients with Acute Myeloid Leukemia Based on the Decision Curve

To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML). 98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve. After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone. The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.

Dysregulated circulating miR-4429 serves as a novel non-invasive biomarker and is correlated with EGFR mutation in patients with non-small cell lung cancer.

This study aimed to investigate the correlation between microRNA (miR)-4429 and epidermal growth factor receptor (EGFR), the expression, and clinical significance of miR-4429 in patients with non-small cell lung cancer (NSCLC), and the relationship between miR-4429 and EGFR mutation in NSCLC patients. Blood samples were collected from 122 NSCLC patients and 72 healthy volunteers. miR-4429 expression and EGFR mRNA expression were detected by real-time quantitative polymerase chain reaction. Correlation between miR-4429 and EGFR was evaluated by dual-luciferase reporter assay and the Pearson correlation analysis. The ability of serum miR4429 to discriminate between NSCLC patients and healthy controls, and to discriminate between EGFR wild-type (EGFR-W) and EGFR mutant-type (EGFR-M) patients was assessed using receiver operating characteristic analysis. The relationship between miR-4429 and NSCLC patients’ survival was identified by KaplanMeier survival curves and log-rank test. The prognostic value of miR-4429 in NSCLC patients was evaluated by Cox regression analysis. miR-4429 could directly bind to EGFR. Serum miR-4429, decreased in NSCLC patients, was negatively correlated with serum EGFR mRNA expression in NSCLC patients. In addition, miR-4429 had a high diagnostic value for screening NSCLC patients from healthy controls, and was independently correlated with survival prognosis of NSCLC patients. Moreover, miR4429 was decreased in EGFR-M patients, which had a certain screening ability for EGFRM patients. Our findings indicate that miR-4429 is negatively correlated with EGFR in NSCLC, and may function as a diagnostic and prognostic biomarker for NSCLC patients. Additionally, miR-4429 is associated with EGFR mutation in NSCLC patients.

The Association of Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2 with Prognosis of Colorectal Cancer under FOLFOX Chemotherapy

To clarify association of epidermal growth factor receptor, human epidermal growth factor receptor 2 with prognosis of colorectal cancer under FOLFOX chemotherapy. A total of 108 colorectal cancer patients under FOLFOX chemotherapy in the hospital from October 2017 to October 2019 were chosen as research subjects. The baseline data of patients were recorded before treatment and levels of serum tumor markers carcino embryonic antigen and carbohydrate antigen 125 and serum epidermal growth factor receptor and human epidermal growth factor receptor 2 were measured and recorded. After 6 courses of FOLFOX chemotherapy, prognosis of patients was observed. The effective patients were included in good prognosis group and the remaining ones were included in poor prognosis group. The baseline data and laboratory indicators before treatment were assessed between two groups and association of epidermal growth factor receptor and human epidermal growth factor receptor 2 with prognosis of colorectal cancer under FOLFOX chemotherapy was evaluated. Among 108 colorectal cancer patients completing FOLFOX chemotherapy, 18 (16.67 %) had complete response, 29 (26.85 %) had partial response, 37 (34.26 %) had stable disease and 24 (22.22 %) had progressive disease and 56.48 % (61/108) had poor prognosis. Carcino embryonic antigen, carbohydrate antigen 125, epidermal growth factor receptor and human epidermal growth factor receptor 2 in poor prognosis group presented elevation relative to those in good prognosis group, with statistical significance (p<0.05). Logistic regression analysis demonstrated that carcino embryonic antigen, carbohydrate antigen 125, epidermal growth factor receptor and human epidermal growth factor receptor 2 had association with prognosis of colorectal cancer under FOLFOX chemotherapy (odds ratio >1, p<0.05). The receiver operating curve demonstrated that area under curve of serum epidermal growth factor receptor and human epidermal growth factor receptor 2 levels before treatment alone and in combination to predict prognosis of colorectal cancer under FOLFOX chemotherapy were 0.709, 0.766 and 0.828, respectively, all of which had certain predictive value. The up regulation of serum epidermal growth factor receptor and human epidermal growth factor receptor 2 may be a risk factor for unfavourable prognosis of colorectal cancer under FOLFOX chemotherapy, which can be used for predicting prognosis of colorectal cancer under FOLFOX chemotherapy.

The Clinical Role of Serum Epidermal Growth Factor Receptor 3 in Hepatitis C Virus-Infected Patients with Early Hepatocellular Carcinoma.

Simple SummaryThe identification of diagnostic and prognostic biomarkers for the management of patients with hepatocellular carcinoma is an unmet need. Here we investigate the potential clinical utility of the measurement of serum epidermal growth factor receptor 3 (i.e., ERBB3) in hepatitis C virus-infected patients with early hepatocellular carcinoma. Median values of serum ERBB3 were similar between patients with cirrhosis and those with early hepatocellular carcinoma (HCC); therefore, the measurement of the biomarker in the setting of HCC surveillance appeared unsuitable. Conversely, in patients with early HCC, serum ERBB3 values were significantly associated with overall survival, suggesting that the biomarker may be useful to tailor appropriate treatment strategies in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma. Epidermal growth factor receptor 3 (ERBB3) is a surface tyrosine kinase receptor belonging to the EGFR/ERBB family, involved in tumor development and progression. We evaluated the diagnostic and prognostic value of serum ERBB3 measurement in hepatitis C virus (HCV)-infected patients with early hepatocellular carcinoma (HCC). A total of 164 HCV-infected patients (82 with cirrhosis and 82 with early HCC) were included in the study. HCC was classified according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Among patients with HCC, 23 (28%) had a diagnosis of very early tumor (BCLC = 0), while 59 (62%) had a diagnosis of early HCC (BCLC = A). Median overall survival (OS) in patients with HCC was 79.2 (95% CI 51.6–124.8) months. While ERBB3 serum values were similar between patients with cirrhosis and those with HCC (p = 0.993), in the latter, serum ERBB3 ≥ 2860 RU resulted significantly and independently associated with OS (Hazard Ratio = 2.24, 95% CI 1.16–4.35, p = 0.017). Consistently, the 1-, 3-, and 5-year OS rates in patients with serum ERBB3 ≥ 2860 RU were 90% (36/40), 53% (19/36), and 28% (8/29) in comparison to patients with serum ERBB3 < 2860 RU, which were 98% (40/41), 80% (32/40), and 74% (26/35) (Log-rank test; p = 0.014). In conclusion, serum ERBB3 values resulted an independent prognostic factor of patients with early HCC and might be useful to tailor more personalized treatment strategies.

Progastrin-Releasing Peptide Precursor and Neuron-Specific Enolase Predict the Efficacy of First-Line Treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Among Non-Small-Cell Lung Cancer Patients Harboring EGFR Mutations.

PurposeLung cancer is the leading cause of cancer-related mortality and non-small-cell lung cancer (NSCLC) accounts for 80–90% of all lung cancers. However, biomarkers to predict the prognosis of NSCLC patients upon treatment with tyrosine kinase inhibitors remain unreliable. Different types of EGFR mutations can help predict the efficacy of tyrosine kinase inhibitor (TKI) treatment among advanced NSCLC patients harboring them. However, survival varies among individuals harboring the same mutation after targeted therapy. This study aimed to investigate the value of serum tumor markers (STMs) and EGFR mutations in the prognostic assessment of progression-free survival (PFS) in advanced-stage EGFR-mutated NSCLC.Patients and MethodsA retrospective clinical review was performed on 81 NSCLC patients harboring EGFR mutations and for whom STM data, measured before commencement of first‐line treatment with tyrosine kinase inhibitors, were available. Associations among EGFR mutations, STMs, baseline clinical features, and PFS were analyzed. Kaplan−Meier method was used to plot survival curves, and Cox logistic regression models were used to identify independent prognostic factors.ResultsExon 19 deletion (19-del) in EGFR, negative neuron-specific enolase (NSE), negative pro-gastrin-releasing peptide precursor (ProGRP) value, and “never smoking” status were significantly associated with improved PFS (P=0.007, P=0.001, P<0.001, and P<0.001, respectively). Multivariate Cox analysis revealed that 19-del in EGFR, never smoking, negative ProGRP value, and negative NSE were independent predictors of PFS.ConclusionThis study demonstrated that 19-del in EGFR may predict longer PFS in advanced-stage EGFR-mutated NSCLC treated with TKIs. Additionally, longer PFS can be predicted by serum tumor markers with negative ProGRP value, negative NSE value before initial treatment, and “never smoking.” Therefore, in addition to the EGFR mutation type and smoking status, physicians can also prognosticate the PFS of tyrosine kinase inhibitors treatment according to the values of ProGRP and NSE before treatment.

Association of cytokines levels with epidermal growth factor receptor mutation in lung cancer patients.

Lung cancer is one of the most frequent types of cancer and the leading cause of cancer-related deaths. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (TK) being highly expressed in lung cancers. Activation of EGFR through oncogenic mutations leads to upregulation of gene expression that may heighten the inflammatory response in certain situations. EGFR acts as a key regulator and a cellular hub for inflammatory cytokine signaling, thereby promoting tumor cell proliferation, invasion, migration, metastases, and survival. The aim of the present study is to determine the serum cytokines levels and EGFR mutation status in lung cancer patients to investigate the association between the EGFR mutation status and cytokines levels with lung cancer patients. Blood and tissue samples of lung cancer patients were collected. The EGFR mutations of lung cancer patients were determined by the immunohistochemistry (IHC) and serum cytokines levels of lung cancer patients were determined using ELISA. Statistically significant association of EGFR mutations with adenocarcinoma subtypes and non-smokers were found (P < 0.05). Lung cancer patients with EGFR mutations had significantly higher tumor necrosis factor-alpha levels when compared to lung cancer patients without EGFR mutations (P < 0.01), and EGFR mutation status was not significantly associated with interleukin-6 levels (P = 0.24). EGFR mutation detection by the IHC method is a potentially useful tool to guide clinicians for personalized treatment of lung cancer patients of adenocarcinoma subtype, and cytokines are good biomarkers for the diagnosis, prognosis, and prediction of treatment responses in lung cancer patients as well as act as therapeutic targets. This study will provide biomarkers for lung cancer diagnosis and treatments.

Effect of gefitinib on serum EGFR and CYFRA21-1 in patients with advanced non-small cell lung cancer.

Changes of epidermal growth factor receptor (EGFR) and cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with advanced non-small cell lung cancer (NSCLC) before and after gefitinib treatment were observed to explore the significance of such changes. A total of 175 patients with advanced NSCLC who were admitted to Hubei Cancer Hospital from July 2012 to October 2015 were collected and divided into two groups: the control group (85 patients who received conventional chemotherapy) and the experimental group (90 patients treated with gefitinib combined with chemotherapy). The serum expression levels of EGFR and CYFRA21-1 were detected by enzyme-linked immunosorbent assay (ELISA). The therapeutic efficacy and 3-year survival of the two groups were compared, and the factors affecting the survival of the patients were analyzed. The total effective rate and local effective rate of the experimental group were significantly higher than those of the control group (P<0.05). Before treatment, no significant difference was detected in the levels of EGFR and CYFRA21-1 between the two groups (P>0.05). After treatment, the expression levels of EGFR and CYFRA21-1 in the two groups were significantly lower than those before treatment (P<0.05). According to the 3-year survival rate, the experimental group was divided into the survival group and the non-survival group. Single factor analysis was performed on the general data, showing that the influencing factors of the survival include the KPS score, smoking history, number of lesions, pathological stage, EGFR, and CYFRA21-1. Gefitinib can bring significantly improved therapeutic efficacy, lower expression levels of EGFR and CYFRA21-1, and longer survival time for patients with advanced NSCLC. Indicators including confirmed smoking history, a KPS score less than or equal to 60 points, multiple lesions, pathological stage IV, high expression of EGFR and CYFRA21-1, are important factors affecting the survival of patient with advanced NSCLC.

Serum Epidermal Growth Factor Receptor and p53 in Patients with Acute Myeloid Leukemia

AbstractBackground: Acute myeloid leukemia is a clonal hemat-opoietic disorder that may be derived from either a hemat-opoietic stem cell or a lineage-specific progenitor cell. AML is characterized both by a predominance of immature forms and loss of normal hematopoiesis. p53 is a cell cycle check point control protein that detects DNA damage, controls cell growth, DNA repair and apoptosis. EGFR belongs to a family of receptor tyrosine kinases, it plays an important role in many cancers. Since both markers have a role in cell cycle control, we hypothesized that both p53 and EGFR may have a role in AML.Aim of Study: It was to estimate the levels of p53 and EGFR in the serum of patients with AML.Patients and Methods: The study was carried out on forty newly diagnosed AML patients who were selected from Hemato-Oncology Unit, Internal Medicine Department, Tanta University Hospitals. Also on twenty apparently healthy subjects with matched age and sex served as a control group. All studied subjects were subjected to full history, complete physical examination, estimation of p53 and EGFR levels by ELISA. Data was analyzed by using SPSS.Results: The results demonstrated a significant increase of serum p53 and EGFR levels in AML patients group com-pared to control group. A positive significant correlation was noted between p53 and EGFR. Follow-up of patients' group for 18 months revealed that all patients with low p53 and EGFR levels showed good response to therapy and achieved complete remission while patients with high p53 and EGFR levels showed poor outcome.Conclusion: Estimation of both p53 and EGFR levels could be useful as diagnostic and prognostic biomarkers in AML patients either alone or in combination with other biomarkers.

Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

To study the clinical significance of serum epidermal growth factor receptor (EGFR) gene mutation and serum tumor markers in the prediction of tyrosine kinase inhibitor (TKI) efficacy in patients with lung adenocarcinoma. Ninety patients with pathologically diagnosed lung adenocarcinoma were enrolled. Further, 51 out of 90 patients received the EGFR-TKI therapy, oral gefitinib. The correlations among serum EGFR gene mutations in exons 18-21, serum tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), carbohydrate antigen 125, carbohydrate antigen 15-3 as well as carbohydrate antigen 19-9 (CA19-9) levels, and EGFR-TKI efficacy were determined. There was a high consistency of EGFR gene mutation rate between serum and tissue samples. The serum EGFR gene mutation rate in female patients or non-smokers was significantly higher than that in male patients or smokers, respectively. Serum CA19-9, CA24-2, and CEA levels were significantly correlated with serum EGFR mutation. After receiving gefitinib, the progression-free survivals (PFSs) of patients with high serum CEA level, high serum CA19-9 level, or serum EGFR gene mutation were significantly higher than those of normal patients, respectively. The PFSs were significantly prolonged in patients with EGFR gene mutation and high serum CEA level or patients with EGFR gene mutation and high serum CA19-9 level compared with those in patients with one abnormal biomarker and normal patients. Combined detection of EGFR gene mutations as well as CA19-9 and CEA levels in peripheral blood can predict the efficacy of EGFR-TKI in the treatment of patients with lung adenocarcinoma.

Analysis of gene mutation associated with tyrosine kinase inhibitor sensitivity of epidermal growth factor receptor in cervical cancer patients.

Cervical cancer is frequent in females. Epidermal growth factor receptor has a prominent expression in certain malignant tumors. This study aims to observe the expressional profile of epidermal growth factor receptor (EGFR) in cervical cancer patients, and mutation of EGFR gene related with its sensitivity towards tyrosine kinase inhibitor. Cervical cancer patients from our hospital were recruited as the experimental group, in parallel with chronic cervicitis patients as control group. Serum EGFR level was measured by enzyme-linked immunosorbent assay (ELISA), and EGFR levels in cervical tissues were quantified by immunohistochemistry assay (IHC) staining. Real Time-PCR (RT-PCR) examined mutations of exon 18, 19, and 21 of the EGFR gene, to analyze their correlation with clinical or pathological features. Serum EGFR in experimental group was 1.16 ± 0.04 ng/ml, significantly higher than control group (p < 0.05). EGFR positive rate was 71.1% in cancer tissues, significantly higher compared to controlled or adjacent tissues (p < 0.05). Mutation rats of EGFR exon 19 and exon 21 were 3.3% and 5%, respectively. No mutation was found in exon 18. Such mutations of EGFR gene were related with cancer differentiation grade, tumor-lymph-node-metastasis (TNM) stage, lymph node or distal metastasis (p < 0.05), but not age, Karnofsky performance score (KPS) score or infiltration depth. EGFR is highly expressed in serum and tumors of cervical cancer patients, some of which showed mutations of exon 19 and 21 of EGFR gene with relatively lower frequency. Mutation rates were significantly higher in patients with highly differentiated grade, early TNM stage, and those without lymph node or distal metastasis.

Resonance Rayleigh scattering assay for EGFR using antibody immobilized gold nanoparticles.

A highly selectivity determination of epidermal growth factor receptor (EGFR) has been described in the article. Antibody immobilized cysteamine (Cys) functionalized gold nanoparticles (AuNP) were proposed as immunosensors, and resonance Rayleigh scattering (RRS) was used for detection. First, Cys stabilized AuNPs (Cys-AuNP) were prepared by the reduction of chloroauric acid with sodium borohydride in the presence of Cys. Further, anti-EGFR antibody (Cetuximab, C225) was covalently linked to the Cys-AuNP by carbodiimide-mediated amidation protocol to yield the C225-AuNP immunoprobe. The prepared conjugations were characterized by ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Based on the specific binding of C225 to EGFR, an RRS method was established to determine the concentration of EGFR. Under the optimal conditions, the concentration of EGFR was related to the intensity of RRS in the range 30-130ng ml-1 with a low detection limit of 4.0ng ml-1 . Meanwhile, the proposed immunosensor exhibited excellent selectivity and anti-interference property. The method was applied to the determination of EGFR in human serum and cancer cell lysate samples with satisfactory results.

Abstract B63: Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: A systematic review

Abstract The epidermal growth factor receptor (EGFR) and its ligands are involved in breast cancer pathogenesis and serve as co-targets for dual- and pan-EGFR-inhibitors in breast cancer treatment. There are indications that EGFR and EGFR-ligands are involved in resistance towards certain breast cancer treatments, including trastuzumab and antiendocrine treatment. The aim of the systematic review is to explore the validity of EGFR and EGFR-ligands in blood as prognostic and predictive biomarkers in breast cancer. The systematic review is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Literature searches were conducted in PubMed, Embase, and Cochrane Library to identify publications exploring correlations between levels of EGFR or EGFR-ligands in serum or plasma of breast cancer patients and prognostic or predictive outcome measures. A total of 2152 publications were identified and assessed for eligibility through title screening, followed by abstract screening and eventually assessment of full-text reports. A total of 16 publications were eligible for inclusion, of which 12 studies evaluated EGFR in serum and 5 studies evaluated one or more of the EGFR-ligands in serum. Current evidence indicates associations between low baseline serum-EGFR and shorter survival or reduced response to treatment in patients with advanced or metastatic breast cancer, especially in patients with estrogen and/or progesterone receptor-positive tumors. Though several studies did not find the same significant trends, none of the identified studies reported opposing results. Regarding EGFR-ligands, the prognostic and predictive value of S-Amphiregulin (S-AREG), S-Epidermal Growth Factor (S-EGF), and S-Transforming Growth Factor-α (S-TGFα) in breast cancer has been investigated in several studies, whereas no studies evaluated S-Betacellulin, S-Heparin Binding Epidermal Growth factor, S-Epiregulin, or S-Epigen. Most of the studies evaluating S-AREG, S-EGF, or S-TGFα included few patients and all studies were performed on patients experiencing HER2-positive advanced breast cancer (in one study HER2-status was not reported). Only one larger study was identified. In this study no associations between S-AREG, S-EGF, or S-TGFα and progression-free survival were observed in patients receiving either pertuzumab+trastuzumab+docetaxel or placebo+trastuzumab+docetaxel. However, decreases or increases in tumor marker levels were not evaluated in this study. The utility of both S-EGFR and serum levels of EGFR-ligands as predictive and prognostic markers in breast cancer has only been investigated in highly selected subsets of breast cancer patients, so extensive aspects remain to be uncovered. Based on the current knowledge, it is not possible to make recommendations either for or against clinical application. Large, well-planned studies are needed in order to clarify and validate the clinical impact of EGFR and EGFR-ligands in the clinical management of breast cancer patients. Citation Format: Ina Mathilde Kjaer, Troels Bechmann, Ivan Brandslund, Jonna Skov Madsen. Prognostic and predictive value of EGFR and EGFR-ligands in blood of breast cancer patients: A systematic review [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B63.

The importance of programmed death ligand 1 gene expression, epidermal growth factor receptor gene mutations and serum epidermal growth factor receptor levels in Turkish non-small cell lung cancer patients.

This study aims to investigate the possible relationships between epidermal growth factor receptor gene mutations, serum epidermal growth factor receptor levels, programmed death ligand gene expression levels and the risks and survivals of resectable nonsmall cell lung cancer patients. Deoxyribonucleic acid isolation was performed from peripheral blood samples and tumor tissues. The mutation analysis was performed for epidermal growth factor receptor. Programmed death ligand 1 gene expression levels were examined pathologically and histopathologically following the tissue tracing of 36 non-small cell lung cancer patients (29 males, 7 females; mean age 60.1 years; range, 41 to 79 years) and analyzed using real-time polymerase chain reaction. Epidermal growth factor receptor serum levels were assessed in all patients. As a result of mutation analyses in 21 patients (28.5% of all adenocarcinoma patients), epidermal growth factor receptor mutation was determined in at least one exon in six patients. In epidermal growth factor receptor mutation detected patients, programmed death ligand 1 gene expression levels were associated with lymph node metastasis (p=0.036). However, epidermal growth factor receptor mutations were not statistically significantly associated according to histopathological examination (p>0.05). Of patients carrying exon 20 (c.2303G>T) mutations, 25% had tumors with perineural invasion. There was a statistically significant association between exon 20 insertions and c.2303G>T and lymphatic invasion (p=0.02), lymph node metastasis and exon 20 insertions (p=0.03). Patients with lower serum epidermal growth factor receptor levels (<400 pg/mL) had better survival time than those with higher serum epidermal growth factor receptor levels (p=0.04). Programmed death ligand 1 gene expression and epidermal growth factor receptor mutation might have a combined effect on non-small cell lung cancer. Programmed death ligand 1 gene expression in tumor pathology may also be a significant feature for tumor progression and tumorigenesis. Serum epidermal growth factor receptor levels seem to be associated with survival.

Pivotal Role of Liquid Biopsy in Diagnosing, Managing and Monitoring Early and Advanced Stages of Lung Cancer among Asian Population

RATIONALE: Non-small cell lung cancer (NSCLC) remains the leading cause ofcancer-related deaths among Asian population. Liquid biopsy is a new technology thatprovides information on tumor gene profiling through examination of cell-free DNA(CfDNA) in whole blood. This produces data on genetic alterations found in tumortissue that could be used for prompt and effective management of NSCLC. MATERIALS AND METHODS: Between September 2016 and December 2016, weretrospectively collected and reviewed the medical records of thirty-five patients whowere suspected or diagnosed of lung cancer, then underwent serum epidermal growthfactor receptor (EGFR) for further investigation. Liquid biopsy results were comparedwith the subjects’ final diagnosis. RESULTS: The final diagnoses revealed eighteen (51%) benign and seventeen (49%)malignant cases. Fourteen out of seventeen malignant cases were diagnosed asadenocarcinoma. The remaining three out of seventeen subjects’ diagnoses were:anaplastic giant cell, carcinoid tumor and thyroid cancer with lung metastasis. Thesethree were considered as true negative for EGFR liquid biopsy results. The fourteenmalignant cases were divided into two categories which were surgical and chemotherapyor TKI groups. In the surgical group, five were positive for tissue EGFR mutationfollowed by a negative serum EGFR results post-surgery. One out of the five casesreported negative serum EGFR just four days post-operatively.In the chemotherapy or tyrosine kinase inhibitor (TKI) group, four out of nine weretested prior to treatment with three positive results. One was negative serum EGFR buthad positive tissue EGFR. One case out of nine reported positive EGFR followed by anegative EGFR at thirteen days while on treatment. The last four subjects were testedduring prolonged treatment. Two from the four cases reported negative results. Onedetected resistance and the last case was negative EGFR but later deteriorated. CONCLUSION: Liquid biopsy’s roles include lung cancer screening, treatmentevaluation, assessment of recurrence or resistance, an alternative for tissue biopsy anda complementary blood test with radiographic imaging. This test substantially improvespatient care and outcomes at all stages of lung cancer. Keywords: lung cancer diagnosis, Non-small cell lung cancer, liquid biopsy, epidermalgrowth factor receptor

Evaluation of serum epidermal growth factor receptor (EGFR) in correlation to circulating tumor cells in patients with metastatic breast cancer

Overexpression of epidermal growth factor receptor in breast cancer is associated with estrogen receptor negativity, higher histological grade and larger tumors. The aim of the present study was to evaluate the clinical significance of serum EGFR (sEGFR) in relation to circulating tumor cells (CTCs) in metastatic breast cancer. 252 patients were enrolled in this prospective multicentre study. Blood was drawn before start of a new line of therapy. sEGFR was determined using a sandwich-type ELISA. CTCs were detected using CellSearch. sEGFR was determined in 48 healthy controls and 252 patients, with no significant differences between the two groups. Clinical-pathological parameters did not correlate with sEGFR, irrespective of the cutoff chosen. Patients with sEGFR levels above the 50th and 75th percentile were more likely to present with <5 CTCs per 7.5 ml blood (p = 0.007; p = 0.003). Patients with sEGFR ≥73 ng/ml had significantly longer overall survival than those with sEGFR <73 ng/ml (19.7 vs. 15.2 months; p = 0.007). In the multivariate analysis, presence of ≥5 CTCs, higher grading and higher line of therapy remained independent predictors of shorter OS, while only higher line of therapy and presence of ≥5 CTCs were independent predictors of shorter PFS.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AND CARCINOEMBRYONIC ANTIGEN (CEA) RELATIONSHIP OF LUNG ADENOKARSINOMA IN SAIFUL ANWAR HOSPITA MALANG

Abstract: EGFR mutations is associated with sensitivity to tyrosine kinase inhibitors (TKI’s) therapy which are found in Lung Adenocarcinoma. There are some limitations in detecting EGFR mutation. CEA is also expected to predict treatment efficiency of EGFR-TKI's therapy. In this study, we investigated the relationship between serum Carcinoembryonic antigen (CEA) and Epidermal Growth Factor Receptor (EGFR) Mutations in Lung Adenocarcinoma patient. Methods : The research was conducted in Dr. Saiful Anwar General Hospital Malang. From May 2014 to November 2015, 54 lung adenocarcinoma patients who had underwent measurements of EGFR mutation and serum CEA level were retrospectively recruited. None of them had surgery, radiotherapy, chemotherapy and targeted therapy. EGFR mutation was detected using PCR, serum CEA levels were analyzed using electrochemical luminescence. Result: Abnormal serum levels of CEA were significantly associated with EGFR mutation (95% CI, P=0,043) with an odds ratio of 3.4 (95% CI: 1.010-11.451). The area under the ROC curve for CEA was 0.558 (95% CI, P=0.078). Conclusion: Serum CEA is associated with mutation of EGFR in lung adenocarcinoma patients. Keywords : Lung cancer, adenocarcinoma, EGFR, CEA