Bladder urothelial carcinoma (BUC) is the most lethal malignancy of the urinary tract. Treatment for the disease highly depends on the invasiveness of cancer cells. Therefore, a predictive biomarker needs to be identified for invasive BUC. In this study, we employed proteomics methods on urine liquid-based cytology (LBC) samples and a BUC cell line library to determine a novel predictive biomarker for invasive BUC. Furthermore, an in vitro three-dimensional (3D) invasion study for biological significance and diagnostic validation through immunocytochemistry (ICC) were also performed. The proteomic analysis suggested moesin (MSN) as a potential biomarker to predict the invasiveness of BUC. The in vitro 3D invasion study showed that inhibition of MSN significantly decreased invasiveness in BUC cell lines. Further validation using ICC ultimately confirmed moesin (MSN) as a potential biomarker to predict the invasiveness of BUC (p = 0.023). In conclusion, we suggest moesin as a potential diagnostic marker for early detection of BUC with invasion in LBC and as a potential therapeutic target.

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

Overwhelming and persistent inflammation of retinal pigment epithelium (RPE) induces destructive changes in the retinal environment. However, the precise mechanisms remain unclear. In this study, we aimed to investigate RPE-specific biological and metabolic responses against intense inflammation and identify the molecular characteristics determining pathological progression. We performed quantitative analyses of the proteome and phosphoproteome of the human-derived RPE cell line ARPE-19 after treatment with lipopolysaccharide (LPS) for 45 min or 24 h using the latest isobaric tandem-mass tags (TMTs) labeling approach. This approach led to the identification of 8984 proteins, of which 261 showed a 1.5-fold change in abundance after 24 h of treatment with LPS. A parallel phosphoproteome analysis identified 20,632 unique phosphopeptides from 3207 phosphoproteins with 3103 phosphorylation sites. Integrated proteomic and phosphoproteomic analyses showed significant downregulation of proteins related to mitochondrial respiration and cell cycle checkpoint, while proteins related to lipid metabolism, amino acid metabolism, cell-matrix adhesion, and endoplasmic reticulum (ER) stress were upregulated after LPS stimulation. Further, phosphorylation events in multiple pathways, including MAPKK and Wnt/β-catenin signalings, were identified as involved in LPS-triggered pathobiology. In essence, our findings reveal multiple integrated signals exerted by RPE under inflammation and are expected to give insight into the development of therapeutic interventions for RPE disorders.