Biology subjects

Ou, Y.

Publications and source records attributed to Ou, Y..

3 recordsLinked to original sources

bioRxiv2020

Analysis of genetic signatures of tumor microenvironment yields insight into mechanisms of resistance to immunotherapy

BackgroundTherapeutic intervention targeting immune cells have led to remarkable improvements in clinical outcomes of tumor patients. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, due to the lack of appropriate experimental methods, the reason why the immunotherapeutic resistance still existed on the inflamed tumor microenvironment remains unclear. Materials and methodsHere, based on integrated single-cell RNA sequencing technology, we classified tumor microenvironment into inflamed immunotherapeutic responsive and inflamed non-responsive. Then, phenotype-specific genes were identified to show mechanistic differences between distant TME phenotypes. Finally, we screened for some potential favorable TME phenotypes transformation drugs to aid current immunotherapy. ResultsMultiple signaling pathways were phenotypes-specific dysregulated. For example, Interleukin signaling pathways including IL-4 and IL-13 were activated in inflamed TME across multiple tumor types. PPAR signaling pathways and multiple epigenetic pathways were respectively inhibited and activated in inflamed immunotherapeutic non-responsive TME, suggesting a potential mechanism of immunotherapeutic resistance and target for therapy. We also identified some genetic markers of inflamed non-responsive or responsive TME, some of which have shown its potentials to enhance the efficacy of current immunotherapy. ConclusionThese results may contribute to the mechanistic understanding of immunotherapeutic resistance and guide rational therapeutic combinations of distant targeted chemotherapy agents with immunotherapy.

immunology↗

bioRxiv2020

Pan-cancer analysis identified inflamed microenvironment associated multi-omics signatures

BackgroundImmunotherapy has revolutionized cancer therapy. However, responses are not universal. The inflamed tumor microenvironment has been reported to correlate with response in tumor patients. However, how different tumors shape their tumor microenvironment remains a critical unsolved problem. A deeper insight into the molecular characteristics of inflamed tumor microenvironment may be needed. Materials and methodsHere, based on single-cell RNA sequencing technology and TCGA pan-cancer cohort, we investigated multi-omics molecular features of tumor microenvironment phenotypes. Based on single-cell RNA-seq analysis, we classified pan-cancer tumor samples into inflamed or non-inflamed tumor and identified molecular features of these tumors. Analysis of integrating identified gene signatures with a drug-genomic perturbation database identified multiple drugs which may be helpful for converting non-inflamed tumors to inflamed tumors. ResultsOur results revealed several inflamed/non-inflamed tumor microenvironments-specific molecular characteristics. For example, inflamed tumors highly expressed miR-650 and lncRNA including MIR155HG and LINC00426, these tumors showed activated cytokines-related signaling pathways. Interestingly, non-inflamed tumors tended to express several genes related to neurogenesis. Multi-omics analysis demonstrated the neuro phenotype transformation may be induced by hypomethylated promoters of these genes and down-regulated miR-650. Drug discovery analysis revealed histone deacetylase inhibitors may be a potential choice for helping favorable tumor microenvironment phenotype transformation and aiding current immunotherapy. ConclusionOur results provide a comprehensive molecular-level understanding of tumor cell-immune cell interaction and may have profound clinical implications.

immunology↗

bioRxiv2019

Putative protective neural mechanisms in pre-readers with a family history of dyslexia who subsequently develop typical reading skills

Developmental dyslexia is a learning disability characterized by difficulties in word reading. While the prevalence in the general public is around 10-12%, an increased prevalence of 40-60% has been reported for children with a familial risk. Neural atypicalities in the reading network have been observed in children with (FHD+) compared to without (FHD-) a family history of dyslexia, even before reading onset. Despite the hereditary risk, about half of FHD+ children develop typical reading abilities (FHD+Typical) but the underlying neural characteristics and the developmental trajectories of these favorable reading outcomes remain unknown. Utilizing a retrospective, longitudinal approach, this is the first study to examine whether potential protective neural mechanisms are present before reading onset in FHD+Typical. Functional and structural brain characteristics were examined in 69 pre-readers who subsequently developed typical reading abilities (35 FHD+Typical/34 FHD-Typical) using MRI/fMRI. Searchlight-based multivariate pattern analyses identified distinct activation patterns during phonological processing between FHD+Typical and FHD-Typical in right inferior frontal (RIFG) and left temporo-parietal (LTPC) regions. Hypoactivation in LTPC was further demonstrated in FHD+Typical compared to FHD-Typical, suggesting that this previously reported neural characteristic of dyslexia is primarily associated with familial risk. Importantly, FHD+Typical pre-readers exhibited higher activation in RIFG than FHD-Typical, which was associated with increased interhemispheric functional and structural connectivity. These results suggest that putative protective neural mechanisms are already established in FHD+Typical pre-readers and may therefore support their successful reading development. Further studies are needed to investigate the functional significance and developmental trajectories of these neural mechanisms as well as their enabling factors, which has the potential to inform the design of early preventative/remediation strategies.

neuroscience↗