Miaomiao Sheng

Precision medicine has been well recognized since it was proposed, and the invention of liquid biopsy meets the needs of this era. Circulating tumor DNA (ctDNA), one of the most promising components of liquid biopsies, has quickly become the focus of research in recent years because of its unique advantages in clinical application. This article reviews the clinical application of ctDNA in breast cancer detection in recent years and its potential clinical value.

Dai W, et al. J Breast Cancer. 2019 Mar;22:e19. https://doi.org/10.4048/jbc.2019.22.e19

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

Targeted drugs for unselected patients with advanced non-small-cell lung cancer: a network meta-analysis

Purpose Exon 19 deletion and exon 21 L858R mutation were the most common epidermal growth factor receptor (EGFR) mutations. We examined the clinical impact of these two mutations in patients with non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) treatment. Methods The outcomes of interest were progression-free survival (PFS), overall survival (OS) and objective response rates (ORR), network meta-analysis and direct meta-analysis were conducted to calculate the efficacy of EGFR-TKIs between these two mutations. We also investigated the association between EGFR mutation types and clinical characteristics. Results A total of 4835 patients from 26 trials were assessed. EGFR-TKIs, compared with chemotherapy, significantly prolonged PFS and OS in both exon 19 deletion and exon 21 L858R mutation based on 8 trials. Network meta-analysis revealed that treatment with EGFR-TKIs had greater benefit in exon 19 deletion than in exon 21 L858R mutation. Furthermore, direct meta-analysis from 12 studies showed the similar result; patients with exon 19 deletion had a significantly longer PFS compared with exon 21 L858R mutation (HR, 0.69; 95 % CI, 0.57–0.82; P < 0.001). There were also greater benefit on OS (HR, 0.61; 95 % CI, 0.43–0.86; P = 0.005) and higher ORR (OR, 2.14; 95 % CI, 1.63–2.81; P < 0.001). Additionally, we found that a significant association between the type of mutation and age (P < 0.001) or smoking status (P = 0.022), but no other significant differences were detected in sex, histologic subtype and performance status between these two mutations. Conclusions Patients with NSCLC and EGFR exon 19 deletion had a longer PFS, OS and higher response rates after EGFR-TKI therapy compared with exon 21 L858R mutation.