Journal: Molecular therapy : the journal of the American Society of Gene Therapy

Article Title: PD-L1 P146R is prognostic and a negative predictor of response to immunotherapy in gastric cancer.

doi: 10.1016/j.ymthe.2021.09.013

Figure Lengend Snippet: Figure 1. rs17718883 is associated with better overall survival in GC patients (A) GC patients with rs17718883 have higher overall survival (OS) rate and longer median survival time (MST) relative to counterparts with wild-type (WT) PD-L1. Ka- plan-Meier survival curve showing that the PD-L1 rs17718883 polymorphism correlates with OS in patients with GC. rs17718883 was detected in blood samples of 101 GC patients. (B) IHC analysis of PD-L1 expression in GC tissues. Representative images for PD-L1 expression. Magnification, 10; scale bar, 20 mm. (C and D) The protein expression profile is similar for PD-L1 WT and rs17718883. Correlation between PD-L1 expression level and rs17718883; correlation between rs17718883 and PD-L1 combined positive score (CPS). HR, hazard ratio; CI, confidence interval; ns, no significance.

Article Snippet: To investigate the effects of PD-L1 rs17718883 polymorphism on efficacy of PD-1/PD-L1 blockade therapy in GC cells, T cells were incubated with or without 1 ng/mL PD-1 antibody nivolumab (MedChem Express) for 4 days and then co-cultivated with indicated GC cells that labeled with the LIVE/DEAD Cell-Mediated Cytotoxicity Kit (Life Technologies), at a ratio of 10:1 for 6 h. The cell lysis was measured by flow cytometry.

Techniques: Expressing

Journal: PLoS Genetics

Article Title: Intra-patient Inter-metastatic Genetic Heterogeneity in Colorectal Cancer as a Key Determinant of Survival after Curative Liver Resection

doi: 10.1371/journal.pgen.1006225

Figure Lengend Snippet: (A) Summarized patient-wise, the DNA copy number profiles of liver metastases (n = 134 from 45 patients) show high-frequency gains (vertical axis; red) on chromosome arms 7p,7q, 8q, 13q, and 20q, and losses (blue) on 1p, 4p, 4q, 8p, 17p, and 18q. In this plot, chromosome numbers are indicated on the horizontal axes, and chromosomes and chromosome arms are separated by vertical lines. (B) Hierarchical clustering of metastatic deposits collected at first liver resection (n = 123 from 45 patients)based on DNA copy numbers. In 23 patients, the metastatic deposits clustered in a patient-wise manner (different tones of grey distinguish among metastases from individual patients plotted adjacent to each other). Four patients had solitary metastases. In 18 patients, the metastatic deposits were separated in multiple clusters (individual color for each patient), indicating intra-patient heterogeneity. Clustering was done by complete linkage, based on Euclidean distance metrics. (C)Intra-patient inter-metastatic genetic heterogeneity was measured as the average pair-wise Euclidean distance of genome-wide copy numbers among all metastases from each patient (illustrated for a patient with three liver metastases). (D) Violin plot (left) showing the distribution of intra-patient inter-metastatic genetic heterogeneity among the 41 patients with multiple metastatic deposits collected at first liver resection (range 1.7 to 9.7; median 4.7). The right panel shows representative individual copy number segmentation profiles of two metastases from a patient with a level of heterogeneity above (5.0; blue) and below (2.6; red) the median level.

Article Snippet: All 140 tumor samples were analyzed for DNA copy number variation using the Affymetrix Genome-Wide Human SNP Array 6.0 (Affymetrix Inc., Santa Clara, CA).

Techniques: Genome Wide