Re-Clustering and Profiling of Digestive System Tumors According to Microenvironment Components

BACKGROUND: Immunotherapy has become the most promising therapy in digestive system tumors besides conventional chemotherapy and radiotherapy. But only a few patients can benefit from different types of immunotherapies, such as immune checkpoint blockade (ICB). To identify these ICB-susceptible patients, methods are urgently needed to screen and profile subgroups of patients with different responsiveness to ICB. METHODS: This study carried out analysis on patients with digestive system tumors that were obtained from Cancer Genome Atlas (TCGA) cohorts. The analyses were mainly performed using GraphPad Prism 7 and R language. RESULTS: We have quantified the microenvironmental components of eight digestive system tumor patients in TCGA cohorts and evaluated their clinical value. We re-clustered patients based on their microenvironment composition and divided these patients into six clusters. The differences between these six clusters were profiled, including survival conditions, enriched biological processes, genomic mutations, and microenvironment traits. Cluster 3 was the most immune-related cluster, exhibiting a high infiltration of non-tumor components and poor survival status, along with an inhibitory immune status, and we found that patients with high stromal score indicated a poor response in ICB cohort. CONCLUSIONS: Our research provides a new strategy based on the microenvironment components for the reclassification of digestive system tumors, which could provide guidance for prognosis judgment and treatment response prediction like ICB.