Conventional real-time PCR-based detection of T790M using tumor tissue or blood in patients with EGFR TKI-resistant NSCLC.

Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M mutation in patients with non-small-cell lung cancer, such as being less risky and painful. New techniques with high sensitivity (eg, droplet digital PCR) show promising results during blood biopsy, but the positive rates of identification are still quite unclear. Whether there are other factors, except technology, affecting the results of blood biopsy is unclear. In this study, we used conventional amplification refractory mutation system to detect tumor tissue or blood for T790M mutation in patients clinically resistant to tyrosine kinase inhibitors. A total of 45 patients treated at West China Hospital between 2014 and 2016 were analyzed. The positive rate of T790M mutation was 70.8% based on tissue biopsy and 37.5% based on blood biopsy. Of the 24 patients whose epidermal growth factor receptor gene was genotyped through tissue and blood biopsy, 10 (41.7%) were concordant for T790M mutation status (κ=0.006). Of the 17 patients positive for T790M by tissue biopsy, 7 (41.2%) were positive for T790M by blood biopsy, and 3 of these 7 were only weakly positive. Of the 7 patients negative for T790M by tissue biopsy, 2 (28.6%) were positive by blood biopsy. Our T790M detection rate is higher than that reported by other studies using digital droplet PCR. These results suggest that other factors (eg, clinical features), intrinsically connected with circulating tumor DNA level, also affect the results of blood biopsy, and thus cannot be controlled through technological optimization.

Evaluation of serum matrix metalloproteinase-3 as a biomarker for diagnosis of epilepsy.

OBJECTIVE: Reliable molecular biomarkers for epilepsy have yet to be identified. The present study aims to evaluate the utility of serum metalloproteinase-3 as a diagnostic biomarker for epilepsy. METHODS: Serum MMP-3 levels were assessed in 227 individuals with epilepsy and 97 healthy control subjects. Individuals in the control group had no complaints or signs of any neurological disorder for at least 12months before serum collection. The Luminex FLEXMAP 3D assay was used to determine serum MMP-3 levels. RESULTS: Compared with controls, subjects with epilepsy had significantly lower serum MMP-3 concentrations (p<0.05). Serum MMP-3 concentrations were significantly higher in males than in females (p<0.001). Furthermore, Serum MMP-3 concentrations were strongly correlated with age in both epileptic and control groups. For these reasons, ROC curve analyses were performed in age-matched and gender matched groups. In the population aged 20-40years, when cut-off values of 23.87ng/ml and 12.31ng/ml were chosen for MMP-3 in males and females respectively, the sensitivity and specificity for patients with epilepsy versus controls were 72.22% and 76.67% for males, and 45% and 94.12% for females. And when cut-off MMP-3 concentrations of 20.70ng/ml and 10.92ng/ml were chosen for the ≥40years age group, the sensitivity and specificity to distinguish between epileptic and control subjects were 85.71% and 47.62% versus 85.62% and 100% for male and female groups, respectively. CONCLUSIONS: MMP-3 is reduced in epilepsy patients compared to healthy controls. The potential of MMP-3 as an epilepsy biomarker is limited to certain age brackets and depends on the gender.

Serum matrix metalloproteinase-2: A potential biomarker for diagnosis of epilepsy.

OBJECTIVES: In this study, we evaluate the utility of serum metalloproteinase-2 (MMP-2) as a biomarker for the diagnosis of epilepsy. METHODS: We assessed serum MMP-2 levels in 233 epileptic and 97 healthy control subjects. Control subjects had no complaints or signs of neurological disorders for at least 12 months prior to serum collection. Serum MMP-2 levels were determined using the Luminex technology. RESULTS: Compared with controls, subjects with epilepsy had significantly lower serum MMP-2 concentrations (P<0.05). There was no significant difference between males and females in either group (P>0.05). Serum MMP-2 concentrations were highly correlated with age in both groups, and this correlation was strongest for males. When an MMP-2 cut-off value of 175.40ng/ml was used, the sensitivity for distinguishing subjects with epilepsy from controls was 71.13% and the specificity was 62.66%. CONCLUSIONS: Our results reveal that serum MMP-2 may be a potential biomarker for the diagnosis of epilepsy.