[Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma].

Objective: To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods: In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results: Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%, 7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high, medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%, 5/7 and 6/11 in high, medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15, 2/4 and 3/6, respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions: The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.

[The diagnostic performance of galactomannan detection for invasive pulmonary aspergillosis in non-neutropenic hosts].

Objective: To evaluate the diagnostic performance of galactomannan(GM)detection in serum and BALF for invasive pulmonary aspergillosis (IPA) in non-neutropenic hosts. Methods: A pospective study was performed for 1 356 non-neutropenic hosts admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from September 2014 to October 2015. Serum GM test was performed for all, and BALF GM test for a proportion of the patients. The patients were divided into an IPA group and a non-IPA group. SPSS 20.0 was adopted for statistical analysis. Results: A total of 1 361 cases were enrolled, aging 18-96 years, with an average age of (64±15) years. There were 879 male and 477 female patients. Thirty-nine cases were diagnosed as IPA, accounting for 2.9%. For serum GM test, the sensitivity, specificity, PPV and NPV were 43.6%(17/39), 94.1%(1 239/1 317), 17.9%(17/95)and 98.3%(1 239/1 261)respectively. Ninety-six cases received serum and BALF GM tests at the same time. If the cut-off value of BALF GM test was 0.8, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 60.5%(49/81), 28.9%(13/45), 96.1%(49/51)respectively, but if the value was 1.0, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 74.1%(60/81), 38.2%(13/34), 96.8%(60/62)respectively. The ROC curve area of BALF GM, serum GM and the combined serum and BALF GM was 0.87, 0.75 and 0.90, respectively. Conclusions: The sensitivity of serum GM test in non-neutropenic hosts was low, but it had a high negative predictive value.The best BALF GM cut-off value was 1.0. The combined serum and BALF GM tests improved the diagnostic performance.

A novel label-free fluorescence strategy for methyltransferase activity assay based on dsDNA-templated copper nanoparticles coupled with an endonuclease-assisted signal transduction system.

Evaluating DNA methyltransferase (MTase) activity has received considerable attention due to its significance in the fields of early cancer clinical diagnostics and drug discovery. Herein, we proposed a novel label-free fluorescence method for MTase activity assay by coupling double-stranded DNA (dsDNA)-templated copper nanoparticles (CuNPs) with an endonuclease-assisted signal transduction system. In this strategy, dsDNA molecules were first methylated by DNA adenine methylation (Dam) MTase and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved DNA fragments could not act as efficient templates for the formation of fluorescent CuNPs and thus no fluorescence signal was produced. Under optimized experimental conditions, the developed strategy exhibited a sensitive fluorescence response to Dam MTase activity. This strategy was also demonstrated to provide an excellent platform to the inhibitor screening for Dam MTase. These results demonstrated the great potential for the practical applications of the proposed strategy for Dam MTase activity assay.