Abstract 470P
Background
Colorectal cancer (CRC) accounts for high rates of morbidity and mortality among people with solid tumors worldwide. As traditional treatments are limited and often intolerant for patients with advanced CRC, immunotherapy could be a promising way. In order to explore the potential use of immunotherapy biomarkers, we aimed to assess gene alteration and its correlations with microsatellite instability (MSI), tumor mutation burden (TMB) and tumor neoantigens burden (TNB) in Chinese CRC populations.
Methods
133 samples were collected from May, 2020 to February, 2021. All specimens were detected by OncoDrug-Seq 603-gene panel assay through next generation sequencing (NGS) using Illumina NovaSeq 6000. TMB-H was set up as higher than 75% of total quantile, TNB-H was set up as higher than 80%, and TNB-L was defined as less than 50%. MSI was calculated by msisensor2 software (MSI-H was defined as score greater than 20%).
Results
There were three individuals who had MSI-H and the rest were MSS. 21 individuals had TMB-H and 112 patients had TMB-L. As for TNB level, 32 patients were TNB-H, 43 patients were TNB-M, and 58 patients were TNB-L. There were 179 altered genes among all 133 patients. The top five genes with mutational incidence were TP53 (68%), APC (64%), KRAS (53%), PIK3CA (15%), PTEN (8%). Among top five gene mutation, only one gene mutation was associated with TNB, which was KRAS (p=0.45). While, age and gender were not associated with MSI, TMB and TNB level in Chinese CRC patients. Mutational incidences of significant pathways (from KEGG database) were also analyzed. Six signaling pathways were related, including Wnt signaling pathway (68%), ERK signaling pathway (66%), PI3K -Akt signaling pathway (64%), RAS signaling pathway (53%), and TGFβ signaling pathway (7%).
Conclusions
The landscape of gene alteration and MSI, TMB and TNB among Chinese CRC populations in this study will further assist the utilization of these biomarkers to immunotherapy strategies.
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.