Abstract 483P
Background
The prognosis of colon adenocarcinoma (COAD) remains unsatisfactory, but the efficacy of immune checkpoint inhibitors (ICIs) therapy was limited. Microsatellite instability (MSI), Tumor mutation burden (TMB) and Tumor immune microenvironment (TME) of ICIs have been confirmed to be promising predictive biomarkers of ICIs in pan-cancer. The function of MUC16 gene and the correlation with ICIs therapy efficacy have not been revealed.
Methods
Whole exome sequencing (WES) data of 526 COAD patients and 66 Chinese COAD patients were obtained from the Cancer Genome Altas (TCGA) and 3DMed cohort, separately. TMB was defined as the number of somatic nonsynonymous somatic mutations per megabase in the coding region of WES. The tumor-related immune cells infiltration level difference between mutant and wildtype tumors were inferred using TIMER 2.0 (Wilcoxon test). The association between MUC16 mutation states and the efficacy of ICIs was performed in melanoma patients from Miao2018 pan-cancer ICIs treatment cohort.
Results
In total, the alteration frequency of MUC16 gene in COAD was 28% (148/526) in TCGA cohort and 27% (18/66) in Chinese cohort. In TCGA cohort, the expression of MUC16 of COAD tumor tissues was significantly higher than adjacent normal tissues (p<0.001). The level of infiltration of CD8+ T cell, B cell, T cell regulatory (Tregs) and NK cell were all significantly increased in mutated tumors compared with wild-type tumors (p < 0.05). The mutant tumors with significantly higher inferred M1 macrophages than wildtype (p=0.0014), but not in M2 macrophages. In Chinese cohort, the TMB level was higher in mutant group compared to wild-type group (median TMB, mut vs wt = 18.26 vs 2.72 Mut/Mb, p < 0.0001). The percentage of microsatellite instability-high (MSI-H) in MUC16 mutant tumors was 50.00%, while 8.33% in wild-type tumors (Fisher’s exact test, p = 0.0005). The overall survival (OS) of MUC16 mutation group (n=43) were significantly longer than wild-type group (n=108) (median OS, mutation vs wild-type = 20.33 vs 9.77 months; HR 0.59[95% CI 0.37-0.92]; p = 0.019).
Conclusions
The MUC16 mutation COAD tumors had highly TMB levels and infiltrating lymphocytes, which may serve as a potential biomarker to guide ICB therapy in COAD.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T. Chen: Financial Interests, Personal and Institutional, Member: 3D Medicines Inc..M. Huang: Financial Interests, Personal and Institutional, Member: 3D Medicines Inc.. All other authors have declared no conflicts of interest.