Tumor mutation burden predicts aggressiveness and prognosis of gastrointestinal stromal tumor

Tumor mutation burden (TMB) has emerged as a promising predictive biomarker for assessing immunotherapy efficacy and clinical outcomes across a wide range of cancer types. We aim to investigate the prognostic value of TMB in gastrointestinal stromal tumor (GIST) in the present study.

We collected and analyzed data from two independent datasets on the cBioPortal for Cancer Genomics, spanning 1991-2021 and 2015-2021 respectively. All the tumor samples were analyzed by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) next-generation sequencing. TMB was defined as the total number of somatic non-synonymous mutations per coding area of a tumor genome. The primary outcome was the recurrence-free survival (RFS). Survival analysis was performed by the Kaplan-Meier method and Cox regression analysis were used to perform survival analysis and identify prognostic factors.

In total, 317 GIST patients were enrolled. Higher TMB was significantly correlated with larger tumor size (P=0.01), higher mitotic count (P<0.001), risk grade (P<0.001) and presence of metastasis (P=0.003). Non-gastric GIST and older patients exhibited higher TMB compared to gastric GIST and younger patients (P=0.002 and P=0.02, respectively). TMB was significantly correlated with prognosis and was an independent prognostic factor of RFS [hazard ratio (HR) =1.692, 95% confidence interval (CI): 1.106-2.588, P=0.02]. Moreover, high-risk patients with elevated TMB had significantly worse prognosis (P=0.01).

TMB appears significantly associated with aggressive clinicopathological features in GIST and serves as an independent prognostic marker. These findings suggest that TMB may hold potential for stratifying GIST patients who may require closer follow-up and more frequent surveillance.