Abstract 1177P
Background
TSC1 and TSC2 are important tumor suppressor genes, but their research in NSCLC are still limited, especially their association with immunotherapy. This study aims to investigate the relationship of TSC1/TSC2 variants and immunotherapy in Chinese NSCLC patients.
Methods
Retrospective patients were collected, short variants, copy number variations, gene rearrangements and Tumor Mutation Burden (TMB) were analyzed following CAP/CLIA-certificated workflows. Wilcoxon Rank Sum Test were applied to significance statistics.
Results
TSC1/2 variants were detected in 3.3% patients (n=10,182), with 150 (44.4%) in TSC1 and 192 (56.8%) in TSC2. In TSC1/2-altered patients, 58.5% were male, 47.6% were at advanced stage (stage III or IV) and the median age was 61 years old (range, 29-81 years old). In TSC1 altered cases, the median TMB was 4.7 muts/Mb, ranging from 0 to 88.3 muts/Mb. In TSC2 altered cases, the median TMB was 7.7 muts/Mb, ranging from 0 to 128.7 muts/Mb. Interestingly, TMB in TSC1/TSC2 altered patients and other patients showed significant difference, with a p-value of 1.9x10-09 (11.29 vs 7.35 muts/Mb in mean), with 125 (37.0%) showed TMB-H. Moreover, TSC2 and TSC1 patients showed significant difference in TMB (p-value=0.0007). In TSC1 or TSC2 altered cases, TP53 (53.8%), EGFR (40.8%), BRAF (18.6%), KRAS (14.5%) and CDKN2A (13.0%) were the top 5 co-occurred mutated genes. Furthermore, 248 patients harboring TSC1/TSC2 variants were analyzed by IHC with PD-L1 antibody, 30.6% showed positive (TPS>1%) and recommended immunotherapy treatment. What’s more, we found that in TSC1 cases the advanced stage group showed significant higher PD-L1 positive than early stage group (43.4% vs 17.8%, p-value=9.06e-05), other stages showed no significance.
Conclusions
TSC1/2 variants group showed higher TMB and PD-L1 expression compared to non-TSC1/2 variants group. This information may suggest the potential utilities of TSC1/2 mutation status on immunotherapy in NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Shanghai OrigiMed Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.