Utilizing tumor microenvironment microbial profiles and host gene expressions for survival subtyping in diverse types of cancers

Abstract The tumor microbiome, a complex community of microbes found in tumors, has been found to be linked to cancer development, progression, and treatment outcome. However, it remains a bottleneck in distangling the relationship between the tumor microbiome and patient survival. In this study, we aimed to decode this complex relationship by developing ASD-cancer (autoencoder-based subtypes detector for cancer), a semi-supervised deep learning framework that could extract survival-related features from tumor microbiome and transcriptome data, and identify patients’ survival subtypes. By using samples from The Cancer Genome Atlas database, we identified two statistically distinct survival subtypes across all 20 types of cancer. Our framework provided improved risk-stratification (e.g., for Liver hepatocellular carcinoma, LIHC, log-rank test, P = 8.12E-6) compared to PCA (e.g., for LIHC, log-rank test, P = 0.87), predicted survival subtypes accurately, and identified biomarkers for survival subtypes. Additionally, we identified potential interactions between microbes and genes that may play roles in survival. For instance, in LIHC, Arcobacter , Methylocella , and Isoptericola may regulate host survival through interactions with host genes enriched in the HIF-1 signaling pathway, indicating these species as potential therapy targets. Further experiments on validation dataset have also supported these patterns. Collectively, ASD-cancer has enabled accurate survival subtyping and biomarker discovery, which could facilitate personalized treatment for a broad-spectrum types of cancers.