Abstract
Early detection of ovarian cancer has been a challenge to manage the high mortality rate caused by this deadly disease. The trends in mortality have been reduced by the scientific contributions from the corners across the globe, however accounting for the fifth leading cause of gynecological mortality. The complexities in the clinical presentation, origin of tumor, and gene expression profiles had added to much difficulty in understanding and diagnosis of the disease. Stage 1 diagnosis of ovarian cancer improves the 5-year survival rate to around 92%. Cancer antigen-125 (CA-125) is the gold standard tumor marker found at abnormally high levels in the blood of many women in ovarian cancer. However, many non-cancerous conditions exhibit high levels of CA-125 and several women have normal CA-125 level in the early stage of ovarian cancer, suggesting CA-125 biomarker is not specific enough for the screening of early stage ovarian cancer. In addition, several other biomarkers, including HE4 have been added in the diagnostic field for higher sensitivity and specificity in the diagnosis and progression of ovarian cancer. HE4 is a prospective single serum biomarker which has been approved by the FDA to monitor the disease progression in epithelial ovarian cancer. However, owing to low sensitivity and specificity, combination of a panel of biomarkers has been proposed in the diagnosis of the disease. Based on extensive biomarkers research findings, here we discuss current trends in diagnostic approaches and updated potential several panels of cancer biomarkers for early detection of ovarian cancer. It has been recently reported that CA125 in combinations with two or more biomarkers have outperformed single biomarker assays for early detection of the disease. Moreover, CA-125 with CA 19–9, EGFR, G-CSF, Eotaxin, IL-2R, cVCAM, MIF improved the sensitivity with 98.2 % and specificity of 98.7% in early stage detection of ovarian cancer. Overall, this review demonstrates a panel of biomarkers signature as the potential tool for prototype development in future and other advanced approaches for early diagnosis of ovarian cancer to avoid false-diagnosis and excessive cost.
Highlights
Ovarian cancer does not occur frequently, accounts for the fifth-leading cause of cancer mortality among women worldwide
The five year survival estimate of ovarian cancer when the disease is localised in the ovary at the time of diagnosis is 92 %; diagnosis at late stage dropped the estimate to 29 % (Siegel et al, 2017)
The findings showed that ovarian cancer biomarkers such as HE4 and glycodelin exhibited a change-point in 80 % and 60 % respectively; whereas CA125 level does not show change-point
Summary
Ovarian cancer does not occur frequently, accounts for the fifth-leading cause of cancer mortality among women worldwide. 2011–2015 data report 11.6 per 100,000 annual cases of women and 7.2 per 100,000 deaths per year with ovarian cancer (from https://seer.cancer.gov/statfacts/html/ovary.html; SEER, Surveillance, Epidemiology, and End Results Program) Such poor projection of this disease is due to its advance metastasis at the time of presentation and difficulty in diagnosis in its early stage. Histological perspective of ovarian cancer further outlined four transcriptional subtypes of epithelial ovarian cancer as serous, endometrioid, mucinous, and clear cell ovarian cancer of which serous tumors are the most common, representing 40 % of all epithelial tumors (Quirk and Natarajan, 2005; Muinao et al, 2018b) Another classification identified ovarian cancer as the low grade type I with frequent mutations in BRAF, KRAS (Quirk and Natarajan, 2005), and PTEN; whereas high grade type II that harbour mutations in p53 (Banerjee and Kaye, 2013), BRCA1, and BRCA2. This review attempts to draw the importance of the combination of biomarker panels rather than a single biomarker approach in the early diagnosis of ovarian cancer for higher specificity and sensitivity
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