Liquid biopsy: circulating tumor DNA monitors neoadjuvant chemotherapy response and prognosis in stage II/III gastric cancer.

A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II-III GC. Seventy-nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2-lymphadenectomy. Plasma at baseline, post-NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425-gene panel to detect genomic alterations (GAs). Results show that the mean cell-free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL-1 vs 14.40 ng·mL-1 ). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post-NACT, and postsurgery). The maximum variant allele frequency (max-VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max-VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3-year OS was 73% for the post-NACT ctDNA-negative patients and 34% for ctDNA-positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II-III GC patients.

Comparison of the somatic mutations between circulating tumor DNA and tissue DNA in Chinese patients with non-small cell lung cancer.

BACKGROUND: Non-invasive liquid biopsies of circulating tumor DNA (ctDNA) is a rapidly growing field in the research of non-small cell lung cancer (NSCLC). In this study, factors affecting the concordance of mutations in paired plasma and tissue and the detection rate of ctDNA in real-world Chinese patients with NSCLC were identified. METHODS: Peripheral blood and paired formalin-fixed paraffin-embedded tumor tissue samples from 125 NSCLC patients were collected and analyzed by sequencing 15 genes. Serological biomarkers were tested by immunoassay. RESULTS: The overall concordance between tumor and plasma samples and the detection rate of somatic mutations in ctDNA was 69.2% and 78.4%, respectively. The concordance and detection rate raised with clinical stage were stage I: 14.3%, 14.3%; stage II: 53.3%, 60.0%; stage III: 71.4%, 78.1%; stage IV: 74.1%, 85.2%. With increased tumor diameter, the concordance and detection rate raised from 33.33% to 71.64% and 33.33% to 80.8%, respectively. For patients with partial response, stable disease, progressive disease, and who were treatment-naïve, the concordance and detection rates were 0.0%, 62.7%, 75.2, 73.6%, and 16.7%, 61.9%, 83.3%, 86.5%, respectively. Serological markers: CEA, CA125, NSE, and CYFRA21-1 were significantly higher for patients with detectable somatic alterations in ctDNA than in those who were ctDNA negative (17.08 ng/mL vs. 3.95 ng/mL, 21.63 U/mL vs. 18.27 U/mL, 17.68 U/mL vs. 14.14 U/mL, and 6.55 U/mL vs. 3.81 U/mL, respectively). CONCLUSION: Advanced-stage, treatment naïve or poor therapy outcome, and large tumor size were associated with a high concordance and detection rate. Patients with detectable mutations in ctDNA had a higher level of carcinoembryonic antigen, CA125, NSE, and CYFRA21-1.

Inhibitory effects of silybin on the efflux pump of methicillin­resistant Staphylococcus aureus.

Bacterial multidrug resistance efflux systems serve an important role in antimicrobial resistance. Thus, identifying novel and effective efflux pump inhibitors that are safe with no adverse side effects is urgently required. Silybin is a flavonolignan component of the extract from the milk thistle seed. To order to investigate the mechanism by which silybin inhibits the efflux system of methicillin­resistant Staphylococcus aureus (MRSA), antimicrobial susceptibility testing and the double­plate method were used to evaluate the effect of silybin on MRSA41577. The ability of silybin to inhibit the efflux of ciprofloxacin from MRSA was evaluated by performing a fluorescence assay. Reverse transcription­quantitative polymerase chain reaction analysis revealed that silybin reduced the expression of the quinolone resistance protein NorA (norA) and quaternary ammonium resistance proteins A/B (qacA/B) efflux genes in MRSA. This suggested that silybin may effectively inhibit the efflux system of MRSA41577. Compared with the control, MRSA41577 treated with silybin for 16 h exhibited a 36 and 49% reduction in the expression of norA and qacA/B, respectively. Inhibition of the expression of these genes by silybin restored the sensitivity of MRSA41577 to antibiotics, indicating that efflux pump inhibitors, which act by inhibiting the efflux system of MRSA, may disrupt the MRSA resistance to antibiotics, rendering the bacteria sensitive to these drugs.