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High-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening results from PubMed articles. Currently, iCSDB contains 1375 genome-wide screens across 976 human cell lines, covering 28 tissues and 70 cancer types. Importantly, the batch effects from different CRISPR libraries were removed and the screening scores were converted into a single metric to estimate the knockout efficiency. Clinical and molecular information were also integrated to help users to select cell lines of interest readily. Furthermore, we have implemented various interactive tools and viewers to facilitate users to choose, examine and compare the screen results both at the gene and guide RNA levels. iCSDB is available at https://www.kobic.re.kr/icsdb/.

Intratumoral heterogeneity of human epidermal growth factor receptor 2 (HER2) is common in gastric cancer (GC). However, a direct comparison between the results of HER2 immunohistochemistry (IHC) and next-generation sequencing (NGS)–based cancer panel tests has not been explored in GC. We aimed to determine optimal thresholds of HER2 overexpression to be detected by NGS with the data of 168 metastatic GC cases with known expression levels of HER2 by IHC and the copy number alteration of ERBB2 obtained by NGS test by applying tumor heterogeneity index (THI) and receiver operating characteristic curve. GC tissues were obtained via biopsy (N = 103) and gastrectomy (N = 65). HER2 3+ by IHC was observed in 27 cases (16%), and 14 of 27 HER2 IHC 3+ cases (52%) showed intratumoral heterogeneity (

Background and purpose This study evaluated the clinical significance of preoperative sarcopenia according to adjuvant concurrent chemo-radiotherapy (XP-RT) or chemotherapy alone (XP) in the D2 dissected gastric cancer patient cohort of the ARTIST trial. Materials and methods Skeletal muscles at the L3 vertebra level from preoperative computed tomography images among the ARTIST trial participants were measured using validated in-house software. Skeletal muscle index (SMI) was defined as the measured skeletal muscle area divided by the square of the height, and sarcopenia was defined according to the Korean-specific cutoff, i.e. L3 SMI ≤ 49 cm2/m2 for men and ≤31 cm2/m2 for women. Results Among the 440 patients in whom we were able to evaluate L3 SMI, 75 (17.0%) met the definition for preoperative sarcopenia. No differences in treatment-related toxicities or treatment compliance were observed according to the presence of preoperative sarcopenia in either treatment arm. In the subgroup of patients without preoperative sarcopenia, recurrence was significantly lower in the XP-RT arm than that in the XP arm (p = 0.02). Recurrence-free survival (RFS) was also significantly higher in the XP-RT arm (p = 0.02, hazard ratio 0.633, 95% confidence interval 0.433–0.926) in this subgroup. In the multivariate analysis, and after adjusting for significant prognostic factors, the superior outcome of XP-RT arm regarding RFS was maintained in the subgroup of the patients without preoperative sarcopenia. Conclusions Superior clinical outcomes of adjuvant XP-RT over XP were only observed in patients without preoperative sarcopenia.

Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21&ndash, 3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31&ndash, 3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.

Objective To evaluate the effect of perfluorobutane microbubbles (Sonazoid®, GE Healthcare) on steam popping during radiofrequency (RF) ablation for treating hepatocellular carcinoma (HCC), and to assess whether popping affects treatment outcomes. Materials and methods The institutional review board approved this retrospective study, which included 90 consecutive patients with single HCC, who received percutaneous RF ablation as the first-line treatment. The patients were divided into two groups, based on the presence or absence of the popping phenomenon, which was defined as an audible sound with a simultaneous sudden explosion within the ablation zone as detected via ultrasonography during the procedure. The factors contributing to the popping phenomenon were identified using multivariable logistic regression analysis. Local tumor progression (LTP) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with the log-rank test for performing comparisons between the two groups. Results The overall incidence of the popping phenomenon was 25.8% (24/93). Sonazoid® was used in 1 patient (4.2%) in the popping group (n = 24), while it was used in 15 patients (21.7%) in the non-popping group (n = 69). Multivariable analysis revealed that the use of Sonazoid® was the only significant factor for absence of the popping phenomenon (odds ratio = 0.10, p = 0.048). There were no significant differences in cumulative LTP and DFS between the two groups (p = 0.479 and p = 0.424, respectively). Conclusion The use of Sonazoid® has a suppressive effect on the popping phenomenon during RF ablation in patients with HCC. However, the presence of the popping phenomenon may not affect clinical outcomes.