85P - In silico evaluation of the transcriptomic and immunologic profile of lung adenocarcinomas with deletions or disruptive mutations of SMARCA4

Background

Characterization of the immune microenvironment is key. In tumors with wide presence of genomic alterations like non-small cell lung cancer (NSCLC) the evaluation of the immune profile can help to better select treatment options. In this study we explored the transcriptomic landscape of lung adenocarcinoma tumors (LUAD) with genomic alterations at SMARCA4.

Methods

Data from TCGA was downloaded to evaluate the expression of transcripts up or down regulated when deletions or disruptive mutations of SMARCA4 were present in LUAD. Median values were used and genes with fold change (FC) > than 2.5 were selected. Gene set enrichment analysis was performed with Enricher. TIMER platform was employed to investigate the association with immune cell populations.

Results

Of the 507 evaluated patients, disruptive mutations were present in 43 and gene deletions in 5. Molecular/biological functions enriched within the upregulated genes in tumors with SMACA4 deletions included: ncRNA 3'-end processing (GO:0043628) or ketosteroid monooxygenase activity (GO:0047086), among others; involving representative genes like CT45A10; SAGE1; CT45A3; CT45A5; CT45A1, AKR1C1; AKR1C2, CBR1 or CBR3. In tumors with no deletion the most represented molecular/biological functions included the antigen processing and presentation of lipid antigen via MHC class Ib (GO:0048003) with relevant genes as: CD1E; CD1C; CD1B; CD1A; CX3CR1; P2RY12, among others. Presence of CD1A, CD1B, CD1C, CD1E in tumors with no SMARCA4 genomic alterations strongly associated with the presence of dendritic cells (DC) (Corr Rho 0.41, 0.48, 0.44 and 0.45, respectively) and dendritic resting cells (DRC) (Corr Rho 0.75, 0.70, 0.71 and 0.72, respectively). A direct comparison between SMARC4 deletions and DC and DRC, showed a clear negative correlation (Corr Rho -0.5, -4,3, respectively). Similar findings were observed with SMARC4 mutations (DC Corr -0.69, DRC Corr -0.91).

Conclusions

SMARCA4 deletions in LUAD tumors associated with loss of antigen presenting genes including CD1E; CD1C; CD1B; CD1A that are present in myeloid dendritic cells. We hypothesized that loss of antigen presentation functions can be present in LUAD with genomic alterations of SMARCA4.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.