Predicting response to immune checkpoint blockade in NSCLC with tumour-only RNA-seq.
Br J Cancer
; 128(6): 1148-1154, 2023 04.
Article
in En
| MEDLINE
| ID: mdl-36572732
ABSTRACT
BACKGROUND:
Targeted 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.METHODS:
Using 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]).RESULTS:
We 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.CONCLUSION:
TMB calculated from targeted RNA sequencing has a similar diagnostic ability to TMB generated from targeted DNA sequencing.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Antineoplastic Agents, Immunological
/
Lung Neoplasms
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Br J Cancer
Year:
2023
Type:
Article
Affiliation country:
Australia