Genomic profiling studies have demonstrated that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to frontline chemotherapy. We analyzed the mRNA expressions of signature luminal and basal genes in bladder cancer tumor samples from publicly available and MD Anderson Cancer Center cohorts. We developed a quantitative classifier referred to as basal to luminal transition (BLT) score which identified the molecular subtypes of bladder cancer with 80–94% sensitivity and 83–93% specificity. In order to facilitate molecular subtyping of bladder cancer in primary care centers, we analyzed the protein expressions of signature luminal (GATA3) and basal (KRT5/6) markers by immunohistochemistry, which identified molecular subtypes in over 80% of the cases. In conclusion, we provide a tool for assessment of molecular subtypes of bladder cancer in routine clinical practice.
SUMMARY Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARC and 84 cases of conventional urothelial carcinoma (UC), with the TCGA cohort of 408 muscle- invasive bladder cancers serving as the reference. SARCs show a distinct mutational landscape, with enrichment of TP53, RB1, and PIK3CA mutations. They are related to the basal molecular subtype of conventional UCs and could be divided into epithelial-basal and more clinically aggressive mesenchymal subsets on the basis of TP63 and its target gene expression levels. Other analyses reveal that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of the EMT network, and nearly half exhibit a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.
Two-dimensional (2D) superconducting systems are of great importance for exploring exotic quantum physics. The recent development of fabrication techniques has stimulated studies of high-quality singlecrystalline 2D superconductors, where intrinsic properties give rise to unprecedented physical phenomena. Here, we report the observation of Zeeman-type spin-orbit interaction protected superconductivity (Zeeman-protected superconductivity) in 4-monolayer (ML) to 6-ML crystalline Pb films grown on striped incommensurate Pb layers on Si(111) substrates by molecular beam epitaxy. An anomalously large in-plane critical field far beyond the Pauli limit is detected, which can be attributed to the Zeeman-protected superconductivity due to the in-plane inversion symmetry breaking at the interface. Our work demonstrates that, in superconducting heterostructures, the interface can induce Zeeman-type spin-orbit interactions and modulate the superconductivity.
Since the dramatic enhancement of the superconducting transition temperature (T ) was reported in a one-unit-cell FeSe film grown on a SrTiO substrate (1-UC FeSe/STO) by molecular beam epitaxy (MBE), related research on this system has become a new frontier in condensed matter physics. In this paper, we present a brief review on this rapidly developing field, mainly focusing on the superconducting properties of 1-UC FeSe/STO. Experimental evidence for high-temperature superconductivity in 1-UC FeSe/STO, including direct evidence revealed by transport and diamagnetic measurements, as well as other evidence from scanning tunneling microscopy (STM) and angle-resolved photoemission spectroscopy (ARPES), are overviewed. The potential mechanisms of the enhanced superconductivity are also discussed. There are accumulating arguments to suggest that the strengthened Cooper pairing in 1-UC FeSe/STO originates from the interface effects, specifically the charge transfer and coupling to phonon modes in the TiO plane. The study of superconductivity in 1-UC FeSe/STO not only sheds new light on the mechanism of high-temperature superconductors with layered structures, but also provides an insight into the exploration of new superconductors by interface engineering.
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