is a potential prognostic biomarker and correlates with immune cell infiltration in non-small cell lung cancer.

BACKGROUND

The tumor microenvironment (TME) plays an important role in tumor progression and immunotherapy responses in non-small cell lung cancer (NSCLC). The programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) checkpoint is a central mediator of immunosuppression in the TME. However, there is still a need to identify additional biomarkers that could reflect the difference in TME and PD-L1 expression in NSCLC patients. To this end, we focused on the expression of G-protein-coupled receptor family C group 5 type A () in NSCLC. , is a retinoic acid-inducible gene that plays multiple roles in NSCLC. However, little is known about the role of in regulating the TME and PD-L1. Our objective was to describe the critical role of expression in NSCLC in the setting of immune cell infiltration.

METHODS

We identified the relationship between GPRC5A expression and the clinicopathologic characteristics of NSCLC patients in the Fudan University Shanghai Cancer Center (FUSCC) cohort. Furthermore, we validated as a predictive biomarker by using public databases to reveal the relationship between expression and immune cell infiltration. To correlate the expression of GPRC5A with the spatial distribution of PD-L1 in NSCLC samples, we performed multiplex immunohistochemistry (mIHC).

RESULTS

Low GPRC5A expression is associated with earlier pathological stage (pStage). Analysis of immune cell infiltration indicates there is a relationship between low expression and increased infiltration of CD8 T cells, activated CD4 T cells, and M1 macrophages within the TME. Furthermore, low expression is associated with an increased immunophenotype score (IPS) in NSCLC. Additionally, analysis of mIHC reveals there is a correlation between low GPRC5A expression and spatial distribution of tumoral PD-L1 expression.

CONCLUSIONS

Our study revealed the relationship between low expression of GPRC5A and earlier pStage in NSCLC. Furthermore, we observed that low expression of is associated with increased infiltration of immune cells, higher IPS, and spatial distribution of PD-L1-positive tumor cells. Therefore, we speculate that low expression of is associated with immunotherapy, but further validation is still required.