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Tumor Discovery Immunohistochemistry profiling of ovarian cysts
OPN plays a prognostic role by predicting the progression serum in women with ovarian cancer compared to women
of disease in late-stage epithelial ovarian cancer with a with benign ovarian cysts. Notably, CKB expression is
specificity of 34% and sensitivity of 81%. The possibility high in early-stage ovarian tumors, making it a potential
of measuring OPN in urine samples of patients with high- biomarker for early detection of ovarian cancer. 56,57
grade ovarian cancer presents an opportunity for early Human prostasin (PSN): PSN is located on chromosome
diagnosis of ovarian cancer. 50 16p11.2 and is a 40 kDa, trypsin-like proteinase responsible
Bikunin: Bikunin is a glycoprotein with several functions, for activating epithelial sodium channels. PSN has been
known to mediate the suppression of invasion and designated as a novel biomarker for ovarian cancer,
metastasis of cancer cells. It can be measured in the tissue demonstrating a sensitivity of 51% and specificity of 94%.
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and plasma of patients with malignant conditions and However, a study by Tamir et al. reported a sensitivity of
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serves as a prognostic marker for benign and malignant 92% and specificity of 94% for detecting ovarian cancer
ovarian pathologies. A study reported that high levels of when PSN was combined with CA125. Clinically, PSN
pre-operative bikunin are indicative of ovarian cancer serves as a differential diagnostic biomarker for ovarian
prognosis. This finding was consolidated by Tanaka cancer.
51
et al., who analyzed bikunin protein levels in the plasma Mesothelin: Mesothelin was discovered at the National
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of ovarian cancer patients (n = 327), benign ovarian cyst Cancer Institute, United States, in 1996. It is found in
patients (n = 200), and healthy controls (n = 200). The the mesothelial cells lining the peritoneum, pleura, and
study concluded that bikunin is a useful prognostic marker pericardium. It is an antigen with tumor differentiation
of ovarian pathology, demonstrating 70% specificity and properties, exhibiting a widespread expression in tumors,
75% sensitivity. particularly in 70% of ovarian cancers. Tumor cells
Vascular endothelial growth factor (VEGF): VEGF expressing mesothelin showed a greater tendency to
is a protein that enhances vascular permeability and migrate and metastasize. As a potential novel biomarker
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plays a role in regulating physiological and pathological for ovarian cancer, higher levels of mesothelin are
angiogenesis, as well as tumorigenesis. Elevated levels of associated with poor overall survival rates in patients.
VEGF levels have been observed in ovarian cancer patients. McIntosh et al. demonstrated that a panel combining
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In a study by Matsuzaki et al., 12 out of 18 tumor samples mesothelin and CA125 biomarkers yielded enhanced
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from late-stage serous epithelial ovarian cancer patients sensitivity for early detection of ovarian cancer. 62,63
showed strong positivity for VEGF, while six revealed low Transthyretin (TTR): TTR, a natural serum protein, is
to negative expression of VEGF. The study reported that synthesized in the liver, retina, and choroid plexus. As a
the levels of VEGF sensitivity and specificity were 79% and major carrier for serum thyroxine and retinal complex, it is
74%, respectively. 53 responsible for transporting thyroid hormone and retinol-
Human epididymis protein 4 (HE4): HE4 was first binding proteins. TTR has been identified as a potential
discovered as a biomarker of ovarian cancer in 1999. It diagnostic biomarker for early-stage ovarian cancer
is a peptide protease inhibitor that plays a critical role (I-II), with reduced levels correlating with the disease. It
in the innate immune response of epithelial tissues and is found to negatively regulate epithelial ovarian cancer,
belongs to the whey acidic four-disulfide core (WFDC) and further reductions in TTR levels are associated with
protein family. HE4 was identified in the epithelium of the progression of ovarian cancer. TTR has a sensitivity
the distal epididymis. Since its discovery, HE4 has been of 47% and specificity of 95%, respectively, in detecting
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observed to be significantly elevated in ovarian cancer ovarian cancer. However, when combined with HE4,
and endometrial cancer, with a specificity of 95% and a TTR demonstrated improved sensitivity and specificity as
sensitivity of 73%. Interestingly, studies indicated that HE4 compared with CA125, independently. 63,64
protein is not expressed on the surface epithelium of the Transferrin: Transferrin is a protein synthesized in
ovaries; however, its expression is found in 100% of human hepatocytes that plays a crucial role in transporting plasma
endometrioid epithelial ovarian cancer cases and slightly iron to the cells. It has been implicated in promoting tumor
less in serous ovarian carcinoma. 55 development and survival through its anti-apoptotic
Creatine kinase B (CKB): CKB is known for its effects. While transferring has clinical applications in
function in the metabolism of vertebral cells and exhibits ovarian cancer detection, it exhibits low sensitivity (73%)
unregulated expression in some cancers. CKB is a cytosolic and specificity (74%). However, its diagnostic performance
form of creatine kinase. Studies have documented elevated can be improved when used in combination with other
expression of CKB in ovarian cancer. Research indicates biomarkers. A study reported that transferrin levels are
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that CKB activity is significantly higher in pre-operative negatively regulated in the sera of patients with ovarian
Volume 4 Issue 1 (2025) 19 doi: 10.36922/td.5369

