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Browsing by Author "Liu, Yuting"
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Item Computational Image Analysis Identifies Histopathological Image Features Associated With Somatic Mutations and Patient Survival in Gastric Adenocarcinoma(Frontiers Media, 2021-03-31) Cheng, Jun; Liu, Yuting; Huang, Wei; Hong, Wenhui; Wang, Lingling; Zhan, Xiaohui; Han, Zhi; Ni, Dong; Huang, Kun; Zhang, Jie; Medicine, School of MedicineComputational analysis of histopathological images can identify sub-visual objective image features that may not be visually distinguishable by human eyes, and hence provides better modeling of disease phenotypes. This study aims to investigate whether specific image features are associated with somatic mutations and patient survival in gastric adenocarcinoma (sample size = 310). An automated image analysis pipeline was developed to extract quantitative morphological features from H&E stained whole-slide images. We found that four frequently somatically mutated genes (TP53, ARID1A, OBSCN, and PIK3CA) were significantly associated with tumor morphological changes. A prognostic model built on the image features significantly stratified patients into low-risk and high-risk groups (log-rank test p-value = 2.6e-4). Multivariable Cox regression showed the model predicted risk index was an additional prognostic factor besides tumor grade and stage. Gene ontology enrichment analysis showed that the genes whose expressions mostly correlated with the contributing features in the prognostic model were enriched on biological processes such as cell cycle and muscle contraction. These results demonstrate that histopathological image features can reflect underlying somatic mutations and identify high-risk patients that may benefit from more precise treatment regimens. Both the image features and pipeline are highly interpretable to enable translational applications.Item The emerging role of zinc transporters in cellular homeostasis and cancer(Nature Publishing group, 2017-07-28) Bafaro, Elizabeth; Liu, Yuting; Xu, Yan; Dempski, Robert E; Obstetrics and Gynecology, School of MedicineZinc is an essential micronutrient that plays a role in the structural or enzymatic functions of many cellular proteins. Cellular zinc homeostasis involves the opposing action of two families of metal transporters: the ZnT (SLC30) family that functions to reduce cytoplasmic zinc concentrations and the ZIP (SLC39) family that functions to increase cytoplasmic zinc concentrations. Fluctuations in intracellular zinc levels mediated by these transporter families affect signaling pathways involved in normal cell development, growth, differentiation and death. Consequently, changes in zinc transporter localization and function resulting in zinc dyshomeostasis have pathophysiological effects. Zinc dyshomeostasis has been implicated in the progression of cancer. Here we review recent progress toward understanding the structural basis for zinc transport by ZnT and ZIP family proteins, as well as highlight the roles of zinc as a signaling molecule in physiological conditions and in various cancers. As zinc is emerging as an important signaling molecule in the development and progression of cancer, the ZnT and ZIP transporters that regulate cellular zinc homeostasis are promising candidates for targeted cancer therapy.