Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD). Trajectory inference identifies three phases of control tissue fibroblast activation, leading to myofibroblast enrichment in tumour samples: initial upregulation of inflammatory cytokines, followed by stress-response signalling and ultimately increased expression of fibrillar collagens. Myofibroblasts correlate with poor overall survival rates in LUAD, associated with loss of epithelial differentiation, TP53 mutations, proximal molecular subtypes and myeloid cell recruitment. In squamous carcinomas myofibroblasts were not prognostic despite being transcriptomically equivalent. These findings have important implications for developing fibroblast-targeting strategies for cancer therapy

Which surrogate marker can be used to assess the effectiveness of the laboratory and its contribution to clinical outcome?

Assessment of the effectiveness of the clinical laboratory and its contribution to outcomes is gaining increasing emphasis, as part of the overall attempts at making clinical services more transparent and accountable. Tools traditionally used in the assessment of laboratory effectiveness and efficiency have included laboratory accreditation, Q-probes, performance in quality assurance programmes and staffing and cost issues. There is, however, a need to introduce different measures that highlight the laboratory efficiency and contribution to clinical effectiveness and outcomes. Such measures should, ideally, be quantifiable and evidence-based. The use of markers of efficiency and effectiveness could be used as tools to aid this process. Such markers could include incident reporting, the appropriateness of assay repertoire, adding value to reports, the quality of comments made, provision of information on the effect of analytical and biological variation on results, cascading requests to help making diagnoses and unearthing such diagnoses. We suggest that these measures contribute towards the implementation of the clinical governance agenda in relation to the laboratory, and could be used as indicators in laboratory accreditation