Sensitive Detection of Epithelial Ovarian Cancer Biomarkers Using Tag-Laser Induced Breakdown Spectroscopy

Epithelial ovarian cancer (EOC) is the 5th leading cause of death from cancer in women and the main cause of death from gynecological cancer (Barber, 1986). Women have a lifetime risk of ovarian cancer of around 1.5%, which makes it the second most common gynecologic malignancy after breast cancer. Ovarian cancer is often referred to as 'the silent killer' because it frequently causes non-specific symptoms, which contribute to diagnostic delay, diagnosis in a late stage and a poor prognosis. This is one of the reasons for the relatively low, approximately 40%, 5-year survival rate for women diagnosed with advanced EOC. However, when EOC is diagnosed at an early stage this rate increases up to 95% (McGuire et al., 2000). This enhancement demonstrates that early detection of EOC is crucial and it is vital to develop novel diagnostic methods for higher throughput screening of human samples and new biomarkers discovery. One of the important and promising strategies for early cancer diagnosis relies on the development of approaches that can provide accurate detection and identification of specific protein-biomarkers in the serum. These protein-biomarkers would be measured and monitored to yield specific signatures that can be used for the early detection of the disease. Recently, numerous reports demonstrated that a single biomarker (example: CA 125, biomarker of ovarian cancer) approach is highly unlikely to yield results that can accurately distinguish cancer samples from healthy ones. This led researchers to explore the idea of using a basket of biomarkers (Petricoin et al., 2002; Mor et al., 2005) with the expectation that this approach may yield increased specificity and sensitivity for cancer detection. Using this approach, G. Mor et al. reported 95% efficiency discrimination between disease-free and EOC patients, including patients diagnosed with stage I and II disease (Mor et al., 2005). These authors used a blood test, based on the simultaneous identification of four biomarkers: leptin, prolactin, osteopontin, and insulin-like growth factor-II. Petricoin et al. reported the use of mass spectroscopy to develop a classifier that could identify serum from patients with ovarian cancer with 100% sensitivity and 95% specificity (Petricoin et al., 2002). In a follow up study, Zhu et al. reported similar results (Zhu, 2003). However, questions were raised about tests reproducibility and reliability (Wagner, 2003; Garber,