Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer

Abstract

Knowledge of mucins and their multiple roles in various normal and pathological processes has improved greatly in the past two decades. Mucins belong to a family of glycoproteins characterised by densely O-glycosylated repetitive domains and expressed by various surface epithelial cells. Altered expression of mucins is present in various diseases, including cancer. Ovarian cancer is the sixth most common cancer worldwide and the seventh leading cause of cancer-related deaths in women. The most common ovarian cancer is epithelial ovarian carcinoma, which is characterised by few early symptoms, widespread peritoneal dissemination, and ascites at advanced stages that result in poor prognosis. After diagnosis, 5 year survival is only 35–45%. Therefore, improved strategies for early diagnosis and treatment are needed. Because of the surface epithelial origin of epithelial ovarian cancer, mucins are obvious biomolecules for investigation as markers for early diagnosis and as therapeutic targets. We discuss the potential role and clinical usefulness of mucins in early diagnosis, prognosis, and treatment of ovarian cancer.

GLI1 facilitates the migration and invasion of pancreatic cancer cells through MUC5AC-mediated attenuation of E-cadherin

“…Currently, mucins are classified into membrane-associated mucins (MUC1, MUC3, MUC4, MUC12, MUC13, MUC15, MUC16, MUC17, MUC20 and MUC21), secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC19) and secreted non-gel-forming mucins (MUC7 and MUC8) by the HUGO nomenclature. Many previous studies have revealed that mucin expression profiles are a prognostic biomarker in some types of cancers Singh et al, 2008;Briggs et al, 2009). For instance, the expressions of MUC1, MUC2 and MUC5AC were statistically associated with a shorter survival time for pancreatic cancer patients in the United States (Takikita et al, 2009), suggesting that mucin functions not only to protect the normal epithelial surface from harsh environments but also to regulate cancer cell properties.…”

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

“…4 Nonetheless, increased serum levels of CA125 are also found in 68% of patients with benign ovarian tumors and about 1% of healthy women. Therefore, CA125 specificity and sensitivity for diagnosis of EOC are low.…”

Epitope presentation is an important determinant of the utility of antigens identified from protein arrays in the development of autoantibody diagnostic assays

“…The most commonly used biomarker for ovarian cancer is Cancer Antigen 125 (CA125) or Mucin16 which is thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces [9]. Elevated levels of this antigen are detected in over 90% of sera of disseminated ovarian cancer cases but only in 50% of patients in the early stages of the disease [10].…”

“…The high attrition rate of promising autoantigens identified by array screening can in part be explained by the presentation of the epitope of the antigen in the subsequent method of validation and this study provides directions on maximising the potential of candidate biomarkers. The most commonly used biomarker for ovarian cancer is Cancer Antigen 125 (CA125) or Mucin16 which is thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces [9]. Elevated levels of this antigen are detected in over 90% of sera of disseminated ovarian cancer cases but only in 50% of patients in the early stages of the disease [10].…”