iRhom1 rescues cognitive dysfunction in multiple sclerosis via preventing myelin injury.

Multiple sclerosis (MS) is characterized by myelin sheath injury. A disintegrin and metalloprotease-17 (ADAM17), a disintegrin and metalloproteinase, is essential in regulating oligodendrocyte (OL) regeneration and remyelination under demyelinating conditions. iRhom1, a highly conserved inactive protease that belongs to the rhomboid family, is one of key regulators for ADAM17 maturation. However, it is unknown whether iRhom1 also plays a role in central neuron system myelination under demyelinating conditions like MS. In this study, we investigated the function of iRhom1/ADAM17 in cognitive capability in MS by establishing the mice with iRhom1 overexpression in the hippocampus.

Gene expression profiling for the diagnosis of multiple primary malignant tumors.

BACKGROUND: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. METHODS: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. RESULTS: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins. CONCLUSIONS: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

UriBLAD: A Urine-Based Gene Expression Assay for Noninvasive Detection of Bladder Cancer.

Bladder cancer is the most common urinary system neoplasm, with approximately 550,000 new cases per year worldwide. Current methods for diagnosis and monitoring of bladder cancer are often invasive and/or lack sensitivity and specificity. In this study, the authors aimed to develop an accurate, noninvasive urine-based gene expression assay for the detection of bladder cancer. Urine specimens were collected at five Chinese hospitals from patients with bladder cancer, and from healthy and other control subjects. The expression levels of 70 genes were characterized by quantitative RT-PCR in a training cohort of 211 samples. Machine learning approaches were used to identify a 32-gene signature to classify cancer status. The performance of this gene signature was further validated in a multicenter, prospective cohort of 317 samples. In the blind validation set, the 32-gene signature achieved encouraging performance of 90% accuracy, 83% sensitivity, and 95% specificity. The area under the receiver operating characteristic curve reached 0.93. Importantly, the 32-gene signature performed well in the detection of non-muscle invasive tumor and low-grade tumor with sensitivities of 81.6% and 81%, respectively. In conclusion, we present a novel gene expression assay using urine samples that can accurately discriminate patients with bladder cancer from controls. The results might prompt further development of this gene expression assay into an in vitro diagnostic test amenable to routine clinical practice.