Highlights of This Issue

Abstract

A metalloendopeptidase, nardilysin (NRDC), has been suggested to play important roles in inflammation and several cancer types. Yoh and colleagues explored the feasibility of serum NRDC as a prognostic biomarker in patients undergoing surgical resection for intrahepatic cholangiocarcinoma (ICC), the second-most common primary liver cancer with high metastatic rate. As a result, high NRDC levels were associated with poorer prognosis. Serum NRDC levels also were correlated with epithelial mesenchymal transition-related genes in primary tumors. Together, serum NRDC can be a clinically relevant tool for predicting the postoperative outcomes of ICC and therefore contribute to develop a treatment strategy.Up to 50,000 thyroidectomies are performed unnecessarily in the United States annually due to the inability to diagnose benign versus cancerous thyroid nodules. By using genome wide DNA methylation analysis of 109 thyroid tissues, Yim and colleagues found that benign nodules differ from adjacent thyroid tissues and malignant nodules. By using tissue specific epigenetic patterns for benign and malignant thyroid nodules, the authors developed a highly accurate thyroid cancer diagnostic test with an estimated 97% PPV and 100% NPV. Thus, a tissue-specific DNA methylation approach has the potential to provide standard-of-care cancer diagnoses for thyroid nodules.The cellular adhesion molecule VCAM-1 is upregulated on vascular endothelial cells in disease. Using mouse models of brain metastases, Cheng and colleagues show that vascular VCAM-1 is expressed early following metastatic seeding in the brain across a number of different tumor types. Moreover, an MR imaging probe targeted to VCAM-1 enabled detection of micrometastatic deposits that were undetectable using the standard clinical diagnostic method of gadolinium-enhanced MRI. This VCAM-1-targeted MRI approach has the potential to drastically alter the management of patients at risk of brain metastasis in existing treatment paradigms and will lead to greater personalization of care.SGK1 is a conserved member of the AG family of serine/threonine kinases that is highly expressed at the tops of intestinal crypts, suggesting a role in differentiation. SGK1 expression is often reduced in colorectal cancer, with poorly differentiated tumors resulting in a worse prognosis. To explore its role in differentiation, Lee and colleagues conducted a multiomics approach to demonstrate that SGK1 re-expression directly promotes the differentiation of colorectal cancer cells, while inhibiting metastatic potential in a mouse orthotopic xenograft model. This work proposes a greater focus upon therapeutic agents that promote tumor differentiation, rather than simply targeting cell survival, for future research.