ArticleBritish journal of cancer2023
Predicting response to immune checkpoint blockade in NSCLC with tumour-only RNA-seq.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Tumour mutational burden: clinical utility, challenges and emerging improvements.Nature reviews. Clinical oncology · 2024Review
- In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma.Frontiers in immunology · 2024Article
- A unified DNA- and RNA-based NGS strategy for the analysis of multiple types of variants at the dual nucleic acid level in solid tumors.Journal of clinical laboratory analysis · 2023Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeted RNA sequencing (RNA-seq) from FFPE specimens is used clinically in cancer for its ability to estimate gene expression and to detect fusions. Using a cohort of NSCLC patients, we sought to determine whether targeted RNA-seq could be used to measure tumour mutational burden (TMB) and the expression of immune-cell-restricted genes from FFPE specimens and whether these could predict response to immune checkpoint blockade.
methodsUsing The Cancer Genome Atlas LUAD dataset, we developed a method for determining TMB from tumour-only RNA-seq and showed a correlation with DNA sequencing derived TMB calculated from tumour/normal sample pairs (Spearman correlation = 0.79, 95% CI [0.73, 0.83]. We applied this method to targeted sequencing data from our patient cohort and validated these results against TMB estimates obtained using an orthogonal assay (Spearman correlation = 0.49, 95% CI [0.24, 0.68]).
resultsWe observed that the RNA measure of TMB was significantly higher in responders to immune blockade treatment (P = 0.028) and that it was predictive of response (AUC = 0.640 with 95% CI [0.493, 0.786]). By contrast, the expression of immune-cell-restricted genes was uncorrelated with patient outcome.
conclusionTMB calculated from targeted RNA sequencing has a similar diagnostic ability to TMB generated from targeted DNA sequencing.
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