Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

Genomic and transcriptomic characterization of pre-operative chemotherapy response in patients with osteosarcoma.

Osteosarcoma is a heterogeneous disease with regard to its chemotherapy response and clinical outcomes. This study aims to investigate the genomic and transcriptomic characteristics related to pre-operative chemotherapy response. Samples from 25 osteosarcoma patients were collected to perform both whole exome and transcriptome sequencing. Osteosarcoma had significant amount of chromosomal copy number variants (CNVs). Chemotherapy responders showed the higher chromosomal CNV burden than non-responders (p = 0.0775), but the difference was not significant. The percentage of COSMIC signature 3, associated with homologous recombination repair deficiency, was higher in responders (56%) than in non-responders (45%). Transcriptomic analysis suggested that 11 genes were significantly up-regulated in responders and 18 genes were up-regulated in non-responders. Both GSEA and KEGG enrichment analysis indicted that four pathways related to cardiomyopathy were up-regulated in responders, while neuroactive ligand - receptor interaction was up-regulated in non-responders. Finally, a previously published chemoresistant model was validated using our dataset, with the area under the curve of 0.796 (95% CI, 0.583-1.000). Osteosarcoma had the heterogeneous mutational profile with frequent occurrence of CNVs. Transcriptomic analysis identified several signaling pathways associated with chemotherapy responsiveness to osteosarcoma. Transcriptomic signatures provides a potential research direction for predicting the chemotherapy response.

High-efficiency and low-cost production of cadaverine from a permeabilized-cell bioconversion by a Lysine-induced engineered Escherichia coli.

Cadaverine is the monomer of bio-based nylons polyamide 5.4, 5.6 and 5.10. In this study, a litre-scale integrated strategy was developed for high-efficiency and low-cost production of cadaverine using an engineered Escherichia coli. Firstly, the engineered strain BL21-Pcad-CadA induced by cheap l-lysine-HCl instead of IPTG was constructed. Then the permeabilized cells were served as the biocatalyst for the production of cadaverine, because the enhanced permeability facilitated the mass transfer of the substrate and the release of products. After the replacement of industrial materials and the solution of the scale-up permeabilization process, cadaverine concentration reached 205 g/L with the yield of 92.1% after 20 h in a 2 L bioconversion system, achieving the level of industrial production. Furthermore, the costs of industrial materials for 2 L integrated strategy ($2.78) was only 1/11 of the lab reagents ($30.88). Therefore, the proposed strategy is a promising candidate for the industrial process of cadaverine.