Abstract
Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared to normal ovarian tissues and serous type ovarian tumors by Western blot analysis and immunohistochemistry. To further elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2 in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2 protein was detected in the serum of mucinous ovarian cancer patients by Western blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of mucinous ovarian cancer and an ELISA assay may facilitate the early detection of mucinous ovarian cancer using patient serum.
Highlights
Ovarian cancer is one of the most lethal gynecologic malignancies and has among the worst of prognoses
anterior gradient 2 (AGR2) was markedly up-regulated in all mucinous-type ovarian cancers, but no significant expression (< 25% of all cases) was observed in serous-type ovarian cancers compared with normal ovarian tissues (Figure 1)
To confirm the expression of AGR2 mRNA in mucinous ovarian cancers, reverse transcriptase (RT)-PCR analysis was performed in six different human mucinous ovarian cancer tissues and one normal human ovarian tissue (Figure 1C)
Summary
Ovarian cancer is one of the most lethal gynecologic malignancies and has among the worst of prognoses. The lethality of ovarian cancer is primarily attributable to the advanced stage of the disease at the time of the initial diagnosis. The cure rate from currently available therapies is as high as 90% when the cancer is detected in an early stage (American Cancer Society, 2005), the majority of early-stage cancers are asymptomatic and most cases are diagnosed at an advanced stage. Screening for an early-stage diagnosis can significantly reduce mortality. The identification of reliable diagnostic biomarkers for the early detection of ovarian cancer is critical for reducing the mortality rate of ovarian cancer. Identification of meaningful tumor biomarkers with potential clinical application would provide useful information regarding patient diagnosis, prognosis, and possible therapeutic options
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