Liquid biopsy for patients with IBD-associated neoplasia

Abstract

Background It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

The diagnostic ability to classify neoplasias occurring in inflammatory bowel disease by artificial intelligence and endoscopists: A pilot study

“…A multi-left, worldwide collaboration to collect further images of IBDN will achieve highly sophisticated AI systems to diagnose IBDN. Moreover, adding an annotation to this diagnostic imaging AI system using background information of patients, which are risk factors of IBDN, such as the duration of IBD, extent of colitis, and genetic factors, 20,21 will lead to further progress. Moreover, a computer-aided detection system for IBD surveillance colonoscopy is needed, based on our pilot study.…”

Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives

“…In the last years, it has merged as a revolutionising and mainstream approach and used to interrogate the transcriptome in various illnesses, as well as some chronic immune-mediated disorders. [166][167][168] From this, genome-wide analyses of gene expression alternations and AS signatures in patients with different subtypes of IBD are also performed by RNA-seq. For example, a recent pioneering study by Li et al presented an interesting genomic landscape of AS signatures in UC patients based on RNA-seq data from two cohorts, and found that skipped exon (SE) and alternative first exon (AFE) were the two most remarkably enriched F I G U R E 7 Transcriptomic analysis of AS events in the pathogenesis of IBD.…”

“…RNA‐seq, the current next‐generation sequencing (NGS) approach, is expected to a superior technology to microarrays, which can provide global and digital rather than analogue information on transcripts and their corresponding isoforms. In the last years, it has merged as a revolutionising and mainstream approach and used to interrogate the transcriptome in various illnesses, as well as some chronic immune‐mediated disorders 166–168 . From this, genome‐wide analyses of gene expression alternations and AS signatures in patients with different subtypes of IBD are also performed by RNA‐seq.…”

Canine chronic enteropathy—Current state-of-the-art and emerging concepts

“…For the next decade, clinical biomarker research in canine CIE should focus on prospective longitudinal studies to critically evaluate the utility of currently established biomarker assays in dogs with CIE in the routine clinical setting. Incorporating the information gained from several markers into algorithms of “individualized biomarker panels” [as reported for the combination of serum CRP and fecal calprotectin concentration ( 108 )] is expected to further increase the diagnostic accuracy of each individual biomarker and eventually culminate in a holistic individual approach to affected dogs via ‘liquid biopsy' ( 243 ).…”