Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application of integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this is attributed to the clinical success of immune checkpoint blockades in diverse malignancies. However, effective tools for comprehensively interpreting multi-omics data are still warranted to provide increased granularity into the intrinsic mechanism of oncogenesis and immunotherapeutic sensitivity. Therefore, we developed a computational tool for effective Immuno-Oncology Biological Research (IOBR), providing a comprehensive investigation of the estimation of reported or user-built signatures, TME deconvolution, and signature construction based on multi-omics data. Notably, IOBR offers batch analyses of these signatures and their correlations with clinical phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, and signatures generated from single-cell RNA sequencing (scRNA-seq) data in different cancer settings. Additionally, IOBR integrates multiple existing microenvironmental deconvolution methodologies and signature construction tools for convenient comparison and selection. Collectively, IOBR is a user-friendly tool for leveraging multi-omics data to facilitate immuno-oncology exploration and to unveil tumor-immune interactions and accelerating precision immunotherapy.
BackgroundDurable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains unclear.MethodsWe developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms.ResultsThe predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial (NCT02589496, N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features.ConclusionsCurrent study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy.
BackgroundEvidence increasingly suggested that impaired respiratory function remained in about 40% of patients with coronavirus disease 2019 (COVID-19) after discharge, jeopardizing their activities of daily living and quality of life (QoL) in a long term. Pulmonary rehabilitation (PR) can improve exercise capacity and QoL in individuals with chronic lung disease; however, evidence on the effect of PR for patients with post-COIVD-19 was scarce. This study aimed to conduct a systematic review and meta-analysis to evaluate the effect of PR on lung impairment for patients with post-COVID-19.MethodsFive databases were searched for all the published trials of PR for patients with post-COVID-19 from 2019 to October 2021. Data were extracted using a standardized form. The risks of bias of included studies were assessed using the Cochrane risk of the bias assessment tool. Data were synthesized where possible; otherwise, qualitative analysis was done.ResultsAmong 6,000 retrieved studies, 3 studies with 233 patients after COVID-19 were included. The pooled estimate of PR effect on 6-min walk test (6-MWT) (50.41, 95% CI 34.34 to 66.48; p < 0.0001) was in favor of the experiment group with clinical importance. It is found that PR could improve the symptom of dyspnea and QoL; however, its effect on pulmonary function test was inconsistent across studies. The risk of bias of included studies varied, with major concerns on the risk of blinding of participants and interventions performers.ConclusionThe review showed that PR could improve exercise capacity measured by 6-MWT among patients with mild-to-moderate lung impairment after COVID-19. The interpretation of effects on lung function, dyspnea, and QoL should be cautious due to inadequate and conflicting data reported across studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289562, identifier: CRD42021289562.
Acupuncture showed clinical and long-lasting benefits compared with sham acupuncture for chronic prostatitis/chronic pelvic pain syndrome. Randomized controlled trials with larger sample sizes are needed in the future.
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