The five-year survival rate of epithelial ovarian cancer (EOC) is approximately 35–40% despite maximal treatment efforts, highlighting a need for stratification biomarkers for personalized treatment. Here we extract 657 quantitative mathematical descriptors from the preoperative CT images of 364 EOC patients at their initial presentation. Using machine learning, we derive a non-invasive summary-statistic of the primary ovarian tumor based on 4 descriptors, which we name “Radiomic Prognostic Vector” (RPV). RPV reliably identifies the 5% of patients with median overall survival less than 2 years, significantly improves established prognostic methods, and is validated in two independent, multi-center cohorts. Furthermore, genetic, transcriptomic and proteomic analysis from two independent datasets elucidate that stromal phenotype and DNA damage response pathways are activated in RPV-stratified tumors. RPV and its associated analysis platform could be exploited to guide personalized therapy of EOC and is potentially transferrable to other cancer types.

A complex array of chaperones and enzymes reside in the endoplasmic reticulum (ER) to assist the folding and assembly of and the disulfide bond formation in nascent secretory proteins. Here we characterize a novel human putative ER co-chaperone (ERdj5)

Activation of endoplasmic reticulum (ER) stress-related cell signals has been reported in several neurologic disorders and may contribute to neurodegeneration. Endoplasmic reticulum stress is also linked to ischemic injury. However, activation of an ER stress response has not been investigated in multiple sclerosis (MS) lesions. We detected increased expression of ER stress-associated C/EBP homologous protein, immunoglobulin heavy chain-binding protein, and X-box-binding protein 1 in multiple cell types, including oligodendrocytes, astrocytes, T cells, and microglia in active MS lesions. Semiquantitative analysis of expression in active, chronic active, and chronic inactive lesions indicated that levels of immunoglobulin heavy chain-binding protein were significantly higher in acute lesions than in non-MS controls or MS normal-appearing white matter, and that ER stress-associated C/EBP homologous protein was upregulated to the greatest extent at the edges of chronic active lesions. Because demyelination may be triggered by a tissue response to ischemia-like conditions, changes in the hypoxia-related antigen D-110 were also investigated, and it was found that increased ER stress-associated C/EBP homologous protein expression can occur in either the presence or absence of D-110. A possible link between a perturbed ER and lesion development in MS suggests a signaling pathway that may represent a new therapeutic target in MS.

Our results, showing detection of elevated expression of ER stress molecules in lesional tissue, offer compelling evidence for further investigation of the ER stress signalling pathway as a potential therapeutic target for the treatment of MS.