CA125/MUC16 Is Dispensable for Mouse Development and Reproduction

Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 homozygous mutant mice are null mutants. Muc16 homozygous mutant mice are viable, fertile, and develop normally. Histological analysis shows that Muc16 homozygous mutant tissues are normal. By the age of 1 year, Muc16 homozygous mutant mice appear normal. Downregulation of transcripts from another mucin gene (Muc1) was detected in the Muc16 homozygous mutant uterus. Lack of any prominent abnormal phenotype in these Muc16 knockout mice suggests that CA125/MUC16 is not required for normal development or reproduction. These knockout mice provide a unique platform for future studies to identify the role of CA125/MUC16 in organ homeostasis and ovarian cancer

Serum Biomarkers in Gastric Cancer

Serum tumor markers are blood-based biomarkers that are potentially useful in cancer detection, surveillance following curative surgery, prediction of drug response or resistance, and monitoring therapy in advance setting. International guidelines do not accept tumor markers in the process of gastric cancer (GC) diagnosis. Their usefulness in GC can be mainly acknowledged in monitoring the effectiveness of antineoplastic therapy and the surveillance period and in identifying patients at risk for GC. The majority of the commonly used tumor biomarkers are neither specific nor sensitive; moreover, the issue of the almost complete lack of prospectively validated data remains. The four most frequently used tumor biomarkers in GC follow-up are carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), and carbohydrate antigen 72-4 (CA 72-4). In particular, the value of pretreatment serum CEA also represents an independent prognostic factor; CA 19-9 value is often used for the diagnosis of GC; CA 72-4 is considered the major marker for GC, mainly for detecting advanced stages; and elevated serum CA 125 levels are associated with a variety of benign and malignant causes of pelvic mass, including peritoneal metastasis of GC. Specific gastric biomarkers, i.e., pepsinogen (PG) I, PGII, gastrin-17 (G-17), and anti-Helicobacter pylori (HP) antibodies, are being used to identify patients at risk for development of GC, particularly combined in a panel test (GastroPanel) which provides comprehensive information on both the structure and the function of the entire stomach mucosa. In the era of precision medicine, liquid biopsy may represent a prognostic or predictive biomarker and a noninvasive tool for monitoring disease in terms of evaluation of response to systemic therapy as well as in monitoring clonal evolution. It could also be useful for screening and earlier detection, but patients with early stage disease often harbor a plasma concentration of mutant template molecules which is beyond the limit of detection of the most diffuse technologies

Glycans and glycoproteins as specific biomarkers for cancer

Protein glycosylation and other post-translational modifications are involved in potentially all aspects of human growth and development. Defective glycosylation has adverse effects on human physiological conditions and accompanies many chronic and infectious diseases. Altered glycosylation can occur at the onset and/or during tumor progression. Identifying these changes at early disease stages may aid in making decisions regarding treatments as early intervention can greatly enhance survival. This review highlights some of the efforts being made to identify N- and O-glycosylation profile shifts in cancer using mass spectrometry. The analysis of single or panels of potential glycoprotein cancer markers are covered. Other emerging technologies like global glycan release and site-specific glycosylation analysis and quantitation are also discussed