1237P - Association of LRRC15 protein expression with 5-year survival in lung adenocarcinoma patients

Background

LRRC15 (leucine-rich repeat containing 15) is part of the family of leucine-rich repeat proteins, and is a novel factor recently associated with aggressive cancer phenotypes. It is expressed on the cell surface, mostly in the (non-tumour) stroma of common cancers, and on a subset of lung cancer associated fibroblasts. However, in cancers of mesenchymal origin, LRRC15 is also expressed on tumour cells. Recent studies suggest a role for LRRC15 in invasion and immune modulation. The aim of this study is to understand the clinical relevance of LRRC15 expression in a lung adenocarcinoma cohort.

Methods

Tissue samples from 82 cases of early-stage lung adenocarcinoma were assessed for LRRC15 expression, along with pan-cytokeratin to distinguish tumour and stromal cells, using multiplex immunohistochemistry. Images were captured and then analysed using Zeiss Axio Scanner Z1 and Indica HALO AI image analysis platform, respectively. Tumour and stroma area were classified using Densenet v2, followed by quality control of annotated regions. Subsequently, LRRC15 expression intensity was quantified in tumour and stromal areas, and its association with 5-year survival was assessed.

Results

LRRC15 is expressed in lung adenocarcinoma with differing levels of expression across the patient cohort. Expression is more common in the stroma area, but is also observed less frequently in tumour cells. Kaplan-Meier survival analysis showed that high LRRC15 expression in stroma (non-tumour) area is associated with better 5-year survival in patients, with 67% lower risk of death (HR: 0.33, 95% CI: 0.16-0.68, P < 0.01).

Conclusions

Higher LRRC15 stromal expression in early-stage lung adenocarcinoma is indicative of better 5-year survival. LRRC15 expression in the stroma may be impacting on immune cell function to influence clinical outcome.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of St Andrews.

Funding

Melville Trust.

Disclosure

All authors have declared no conflicts of interest.