Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer.

BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.

Cross-Domain Pattern Classification With Distribution Adaptation Based on Evidence Theory.

In pattern classification, there may not exist labeled patterns in the target domain to train a classifier. Domain adaptation (DA) techniques can transfer the knowledge from the source domain with massive labeled patterns to the target domain for learning a classification model. In practice, some objects in the target domain are easily classified by this classification model, and these objects usually can provide more or less useful information for classifying the other objects in the target domain. So a new method called distribution adaptation based on evidence theory (DAET) is proposed to improve the classification accuracy by combining the complementary information derived from both the source and target domains. In DAET, the objects that are easy to classify are first selected as easy-target objects, and the other objects are regarded as hard-target objects. For each hard-target object, we can obtain one classification result with the assistance of massive labeled patterns in the source domain, and another classification result can be acquired based on the easy-target objects with confidently predicted (pseudo) labels. However, the weights of these classification results may vary because the reliabilities of the used information sources are different. The weights are estimated by mean difference reflecting the information source quality. Then, we discount the classification results with the corresponding weights under the framework of the evidence theory, which is expert at dealing with uncertain information. These discounted classification results are combined by an evidential combination rule for making the final class decision. The effectiveness of DAET for cross-domain pattern classification is evaluated with respect to some advanced DA methods, and the experiment results show DAET can significantly improve the classification accuracy.

Combination of Transferable Classification With Multisource Domain Adaptation Based on Evidential Reasoning.

In applications of domain adaptation, there may exist multiple source domains, which can provide more or less complementary knowledge for pattern classification in the target domain. In order to improve the classification accuracy, a decision-level combination method is proposed for the multisource domain adaptation based on evidential reasoning. The classification results obtained from different source domains usually have different reliabilities/weights, which are calculated according to domain consistency. Therefore, the multiple classification results are discounted by the corresponding weights under belief functions framework, and then, Dempster's rule is employed to combine these discounted results. In order to reduce errors, a neighborhood-based cautious decision-making rule is developed to make the class decision depending on the combination result. The object is assigned to a singleton class if its neighborhoods can be (almost) correctly classified. Otherwise, it is cautiously committed to the disjunction of several possible classes. By doing this, we can well characterize the partial imprecision of classification and reduce the error risk as well. A unified utility value is defined here to reflect the benefit of such classification. This cautious decision-making rule can achieve the maximum unified utility value because partial imprecision is considered better than an error. Several real data sets are used to test the performance of the proposed method, and the experimental results show that our new method can efficiently improve the classification accuracy with respect to other related combination methods.