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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.
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            et al.,  who analyzed bikunin protein levels in the plasma   Mesothelin: Mesothelin was discovered at the National
                52
            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
                             54
            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
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