Clinical and molecular impacts of tumor mutational burden in histological and cytological specimens from cancer patients

BACKGROUND: The tumor mutational burden (TMB) is a promising biomarker for immune checkpoint inhibitor (ICI). However, its relationships with clinical parameters have not been fully explored. We aimed to assess potential factors including age, microsatellite instability (MSI) state, tumor types, and gene mutations that might influence TMB value through analyzing 1,504 tissue samples and 496 blood samples from cancer patients. METHODS: The TMB value of individual samples was calculated by whole-exome sequencing (WES) analysis and major cancer-related gene mutations were evaluated using panel sequencing. MSI was detected with MSI analysis system. RESULTS: The results showed that for blood samples, compared to age 1 (age ≤56 years old) or age 2 (56< age <68 years old) groups, the TMB value in the age 3 group (age ≥68 years old) was significantly higher. The MSI ratio (%) had no linear correlation with TMB, and a significant difference of TMB between Kirsten rat sarcoma viral oncogene homologue (KRAS) other alterations and p.G12 alteration was identified. For tissue samples, compared to age 1 (age ≤53 years old), TMB was higher in the age 2 (53< age <65 years old) group and lower in the age 3 (age ≥65 years old) group. MSI ratio (%) had no linear correlation with TMB. Significant differences in TMB were discovered between adenosquamous carcinoma (ASC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) samples. TMB among KRAS p.G12A, p.G12C, p.G12D, p.G12R, p.G12S, p.G12V, and other KRAS alterations were observed in tissue samples. CONCLUSIONS: In conclusion, analysis of age, tumor types, and KRAS mutations may provide a relative effectivity for estimating TMB.