Plasma neuron-specific enolase level as a prognostic marker in patients with non-small cell lung cancer receiving gefitinib

Abstract

Abstract. Determination of the presence of epidermal growth factor receptor (EGFR) gene mutation is useful for predicting the efficacy of gefitinib. However, the survival rate following the initiation of treatment with gefitinib varies among individuals. A retrospective study was conducted to investigate the associations of the pretreatment serum pro-gastrin-releasing peptide (pro-GRP) and plasma neuron-specific enolase (NSE) levels to the patient survival rate following initiation of treatment with gefitinib in non-small cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients with NSCLC harboring EGFR gene mutations who received gefitinib therapy between 2004 and 2012 were included in the study. Data from a total of 41 patients were analyzed. The serum pro-GRP level was measured in 31 patients and the plasma NSE in 22 patients. The progression-free survival (PFS) (P=0.013) and overall survival (OS) (P=0.014, log-rank test) rates decreased as the plasma NSE level increased. Statistical analysis using a Cox proportional hazards regression model adjusted for age, gender, performance status (PS) and disease stage showed that higher NSE levels were associated with shorter PFS (P=0.021) and OS (P=0.0024). By contrast, no association was detected between the serum level of pro-GRP and survival rate. The results suggest that pretreatment NSE measurement could be clinically useful in patients with NSCLC scheduled to receive gefitinib treatment. IntroductionEpidermal growth factor receptor (EGFR) gene mutation is an important predictor of the response to EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. Gefitinib treatment yields a longer progression-free survival (PFS) rate than cytotoxic drug therapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations, including exon 19 deletion and exon 21 L858R (1-3). However, an important clinical problem is that in the majority of cases, the tumor cells soon acquire resistance to gefitinib.Several mechanisms of acquired resistance to gefitinib have been proposed. Hepatocyte growth factor has been shown to induce resistance to gefitinib of lung adenocarcinomas harboring EGFR gene mutations (4). An investigation of 37 cases with acquired resistance to gefitinib revealed the presence of the EGFR T790 mutation, MET amplification, transition from NSCLC to small cell lung cancer (SCLC), or PIK3CA mutation in these cases (5).Blood levels of pro-gastrin releasing peptide (pro-GRP) and neuron-specific enolase (NSE) have been reported to be frequently elevated in patients with SCLC (6), and their measurement has been utilized for diagnosis or evaluation of the treatment outcomes in these patients. Furthermore, elevation of the pretreatment plasma NSE level has also been associated with poor outcomes in patients with NSCLC (7-11). We hypothesized that the blood level of pro-GRP and/or NSE may be associated with the clinical course following initiation of gefitinib therapy in patients with NSCLC harboring EGFR gene mutations. To endorse its va...

Clinical value of Pro‑GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC‑CIK biological therapy

“…A previous study proved that Pro-GRP is highly expressed in SCLC (10), and the specificity and sensitivity of Pro-GRP detection for SCLC diagnosis are higher than those of NSE (22,23). In line with this, the present study also indicated that Pro-GRP is a specific tumor marker of SCLC that had a relatively high expression prior to therapy and exhibited on obvious decrease thereafter.…”

Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib

“…A total of 65 patients fulfilled the criteria and were included in the analysis. Of these, 41 patients who were receiving treatment with gefitinib were also enrolled into our previous study (4). Female patients were slightly dominant, accounting for 53.8% of the population.…”

“…Our previous study reported the existence of an association between the pre-treatment plasma neuron-specific enolase level and the patient survival in EGFR mutation-positive NSCLC patients initiated on gefitinib treatment (4). Neuron-specific enolase is a marker of neuroendocrine tumors, including small cell lung cancer, and functions as a glycolytic enzyme.…”

CA 19-9 and CA 125 as potential predictors of disease recurrence in resectable lung adenocarcinoma

“…NSE is also found in erythrocytes, plasma cells and platelets and may be released to serum due to hemolysis in the procedure of venipuncture [ 14 ]. In patients with NSCLC, NSE has been suggested as a prognostic marker [ 15 ] and some studies have presented an association between increased NSE and shorter survival in EGFR -mutated NSCLC treated with tyrosine kinase inhibitors (TKI´s) [ 16 , 17 ].…”