Abstract 181P
Background
Recently, results of many studies suggested that patients with squamous cell lung cancer (SqCLC) could benefit from immune checkpoint inhibitors (ICIs). However, not all patients receiving ICIs could respond well and many biomarkers were selected and employed to identify the subset of patients most likely to derive clinical benefits. Some studies investigated components of proteasome in melanoma, which showed a superior value than PD-L1, TMB and CD8+ T cell on predicting ICIs’ effect. Here, we performed a comprehensive analysis on proteasome-related genes and their correlation with immunity and immunotherapy in SqCLC.
Methods
An integrated analysis of transcriptomic data from TCGA and GEO database was performed. Gene set variation analysis (GSEA) was employed to investigate the relative activity of signal pathways. CIBERSORT, quanTIseq and single-sample GSEA were used for evaluating tumor immune microenvironment (TIME). Survival analysis and receiver operating characteristic were used to estimate the value of each proteasome-related gene on predicting ICIs’ effect.
Results
A total of 1870 SqCLC patients from 21 cohorts were analyzed in this study. In the result of pathway enrichment analysis, PSMB10, PSMB9, PSMB8, PSME1 and PSMC3IP were shown high correlation with immunity-related pathways, and there were 16, 13, 13, 9 and 8 cohorts that enriched more than 50% of all immunity-related pathways for the five genes, respectively. In terms of TIME analysis, PSMB10, PSMB9, PSMB8 and PSME1 has 47, 46, 41 and 41 statistically significant results, respectively, from totally 63 CD8+ T cell calculated by three algorithms in 21 cohorts, and all of these four genes were positively correlated with high infiltration of CD8+ T cell. As for the evaluation of predictive value on immunotherapy, only PSMB10 was statistically significant (mPFS: 7.33 months vs 0.70 month, p = 0.03; AUC: 0.89, 95%CI 0.65–1).
Conclusions
Among 54 proteasome-related genes, PSMB8, PSMB9 and PSMB10, three important catalytic subunits of immunoproteasome, can distinguish TIME and have high activity of immune-related pathways in SqCLC, in which PSMB10 has the potential as a biomarker of ICIs’ effect.
Legal entity responsible for the study
The authors.
Funding
This work was supported by the China National Major Project for New Drug Innovation (2017ZX09304015, 2019ZX09201-002).
Disclosure
All authors have declared no conflicts of interest.