TIMEDB: tumor immune micro-environment cell composition database with automatic analysis and interactive visualization.

Deciphering the cell-type composition in the tumor immune microenvironment (TIME) can significantly increase the efficacy of cancer treatment and improve the prognosis of cancer. Such a task has benefited from microarrays and RNA sequencing technologies, which have been widely adopted in cancer studies, resulting in extensive expression profiles with clinical phenotypes across multiple cancers. Current state-of-the-art tools can infer cell-type composition from bulk expression profiles, providing the possibility of investigating the inter-heterogeneity and intra-heterogeneity of TIME across cancer types. Much can be gained from these tools in conjunction with a well-curated database of TIME cell-type composition data, accompanied by the corresponding clinical information. However, currently available databases fall short in data volume, multi-platform dataset integration, and tool integration. In this work, we introduce TIMEDB (https://timedb.deepomics.org), an online database for human tumor immune microenvironment cell-type composition estimated from bulk expression profiles. TIMEDB stores manually curated expression profiles, cell-type composition profiles, and the corresponding clinical information of a total of 39,706 samples from 546 datasets across 43 cancer types. TIMEDB comes readily equipped with online tools for automatic analysis and interactive visualization, and aims to serve the community as a convenient tool for investigating the human tumor microenvironment.

P21 and P27 promote tumorigenesis and progression via cell cycle acceleration in seminal vesicles of TRAMP mice.

Transgenic adenocarcinoma mouse prostate (TRAMP) model is established to mimic human prostate cancer progression, where seminal vesicle lesions often occur and has been described as phyllodes-like epithelial-stromal tumors. However, the molecular mechanism regulating tumorigenesis and progression in seminal vesicles of TRAMP mice remains largely unknown. In this study, C57BL/6 TRAMP mice were found to have a significantly shorter lifespan than wild-type (WT) mice and all of the seminal vesicles were markedly increased in size and weight with age from 24 weeks exhibiting a clearly papillary-phyllode pattern, though no obvious difference was observed in multiple organs including heart, liver, spleen, lungs, kidneys, testicles and bone between TRAMP and WT mice, and less than 10% of TRAMP mice developed prostate tumors. Western blotting showed Cyclin (CCN) B1 and CCND1 were remarkably overexpressed in seminal vesicle tumors of TRAMP mice at 24 weeks of age and increased with age till the end of trial, which was confirmed by Immunohistochemistry (IHC). P21 and P27 were also significantly augmented, whereas P53 and phosphorylated P53 (p-P53) were constantly expressed in normal controls and P53 did not appear to be mutated. Not only cyclin-dependent kinase (CDK) 1 and phosphorylated forkhead box protein (FOX) O1 but also CDK4, CDK6 and phosphorylated retinoblastoma-associated protein (RB) had similar increase trends, so did epidermal growth factor receptor (EGFR), AKT serine/threonine kinase (AKT), and their respective phosphorylation levels. Signal transducer and activator of transcription (STAT) 3, p-STAT3, enhancer of zeste homolog 2 (EZH2) and EZH2 mediated trimethylation of histone H3 lysine 27 (H3K27me3) were considerably elevated, too. Taken together, this finding suggests P21 and P27 promote carcinogenesis and development in seminal vesicles of TRAMP mice via accelerating cell cycle progression, in which oncogenic transformation of P21 and P27 might be through regulation of EGFR-AKT signaling.