Abstract 85P
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.
Resources from the same session
77P - Normative data on the sexual health questionnaires - QLQ-SHQ22, and the sexual domains of the QLQ-BR23/BR45 - for Norwegian general population with and without cancer
Presenter: Ragnhild Åsberg
Session: Poster session 09
78P - Peroxiredoxin-1 knockout negatively affects the viability of ph+ B-cell acute lymphoblastic leukemia cells and sensitizes them to tyrosine kinase inhibitors
Presenter: Jaromir Hunia
Session: Poster session 09
79P - Co-delivered crizotinib and gefitinib based on nanoparticle for synergically overcoming resistance lung adenocarcinoma treatment
Presenter: Haiyu Zhou
Session: Poster session 09
80P - Steroidal oximes: A new potential therapeutic approach for cancer treatment
Presenter: Mafalda Laranjo
Session: Poster session 09
81P - miR-23b and -133a role on TRAIL-induced apoptosis pathway components expression and TRAIL sensitization in lung adenocarcinoma cells
Presenter: Denise Leite
Session: Poster session 09
83P - Impact of VHL-associated tumor treatment on mental health: An international patient survey
Presenter: Othon Iliopoulos
Session: Poster session 09
84P - Microenvironment immune differences between sexes in multiple myeloma
Presenter: Maria de los Angeles Clavo
Session: Poster session 09
86P - Effect of chemotherapy-induced autophagic secretome on natural killer cell activity
Presenter: Ayfer Karlitepe
Session: Poster session 09
87P - WIP1 phosphatase promotes etoposide induced autophagy in medulloblastoma and neuroblastoma
Presenter: Hatice Pilevneli
Session: Poster session 09
88P - PPM1D/WIP1 phosphatase mediates basal and genotoxic stress-induced autophagy via ULK-1 de-phosphorylation
Presenter: Ceylan Ak
Session: Poster session 09