Page 28 - TD-4-1

Tumor Discovery Immunohistochemistry profiling of ovarian cysts

cancer. A combination of transferrin, CA-125, TTR, and CDH1, and PAR-4. The use of methylation-specific PCR
72
ApoA1 using a proteomic analytical method, the panel recorded 82% sensitivity and 100% specificity of a panel of
achieved a sensitivity of 89% and specificity of 92% for tumor-specific methylated DNA (BRCA1, RASSF1A, APC,
early detection of ovarian cancer. 66,67 p14ARF, p16INK4a, and DAPK) in the serum of ovarian
Apolipoprotein A-I (ApoA-I): ApoA-I is a primary cancer patients. 64
component of high-density lipoprotein and has been shown MicroRNAs (MiRNAs): MiRNAs have garnered
to have reduced levels in the serum of patients with ovarian attention as potential epigenetic biomarkers of ovarian
cancer. The mechanism linking ApoA-I to cancer remains cancer. They are a family of non-protein-coding single-
unclear, but it has been proposed that it may be associated stranded RNA molecules (18 – 24 nucleotides) that serve as
with free radical-mediated damage to cell membranes, downregulators of gene expression. They specifically bind
leading to lipid peroxidation. A panel of ApoA-1, CA125, to messenger RNAs. MiRNAs are involved in regulating
and β2-M biomarkers has been identified as critical for over 60% of the total human genes and play key roles in
the early detection of ovarian cancer, enhancing higher the cell cycle, differentiation, development, metabolism,
specificity of 98% and higher sensitivity of 94%. 67,68 inflammation, proliferation, and immune response. Studies
Tumor antigen-associated auto-antibody (TAAbs): have noted distinct miRNA expression profiles in different
73
TAAbs are produced by an over-expression of proteins ovarian cancers, suggesting their potential use as diagnostic
or mutations in cancer patients, with different types and prognostic biomarkers of ovarian cancer as well as other
74
75
corresponding with specific tumor types. They represent cancer types. Previous study on the role of miRNA in
a novel serum biomarker for the early detection and ovarian cancer has revealed that miR-21, miR-200a, miR-
diagnosis of high-grade serous epithelial ovarian cancer, 200b, miR-200c, miR-141, miR-214, miR-203, and miR-205
among other cancers. One of the most studied TAAbs in are potential biomarkers for ovarian cancer diagnosis.
ovarian cancer is serum antibodies against p53. Different Aldehyde dehydrogenase-1 (ALDH-1): ALDH-1 is
panels (p53, PTPRA, and PTGFR) have been designed a protein belonging to the ALDH family, encoded by
for early detection and differential diagnosis of ovarian the gene ALDH1A1 gene located on chromosome 9q21.
tumors. The study by Gadomska et al. identified 11 It plays a role in the oxidation of aldehydes through a
69
69
TAAbs: ICAM3, CTAG2, p53, STYXL1, PVR, POMC, pyridine-dependent mechanism. Studies have confirmed
NUDT11, TRIM39, UHMK1, KSR1, and NXF3. These ALDH1’s role in ovarian cancer stem cell differentiation
TAAbs helped to distinguish high-grade serous ovarian and expression of ALDH1 in epithelial ovarian cancer
cancers from healthy controls with 45% sensitivity and stem cell clones, making it a potential biomarker for
98% specificity. tumorigenic stem cells. 76,77 It has been suggested that
B7-H4: B7-H4 is a surface protein composed of 282 increased expression of ALDH1A1 in ovarian cancers
amino acids, primarily found in cells of the immune supports its potential as a potential biomarker for early
system. It is a negative regulator of T-cell response and detection of ovarian cancer. 77
plays a role in the development of various malignancies. Folate receptor alpha 1 (FOLR1): FOLR1 is a membrane
B7-H4 is expressed in tissue from endometrial, serous, and protein and is responsible for the transport of folate into
clear cell carcinoma. When combined with CA125, B7-H4 cells, essential for cellular processes, particularly in rapidly
has been shown to detect a higher percentage of early- dividing cancer cells that have an increased demand for
stage ovarian cancer (65%). A study conducted by Simon folate to sustain DNA synthesis. Folate concentration
70
et al. analyzed B7-H4 protein levels in more than 2500 plays a critical role in tumor etiology and progression.
71
serum samples, tissue lysates, and ascites fluids. The study Studies have reported overexpression of FOLR1 in various
revealed high levels of B7-H4 protein in ovarian cancer tumors of epithelial origin, including ovarian cancer,
tissue lysates. Meanwhile, there was a significant elevation with specific detection in serous ovarian cancer. These
of B7-H4 in patients with benign pathology. 71 findings suggest that FOLR1 is a potential biomarker for

Methylated DNA: Methylated DNA is a versatile the detection of ovarian cancer, as well as for prognosis
potential biomarker for several oncological pathologies. It and assessment of chemotherapy responses. Quantitative
78
can serve as a diagnostic, predictive, prognostic, and staging PCR and flow cytometry were used to study the diagnostic
biomarker. Methylated DNA biomarkers are preferred and prognostic utility of FOLR1 and FOLR3 in effusion
over types due to their stability, region restriction, and cytology from ovarian cancer, breast cancer, and malignant
amplification potentials. Commonly downregulated and mesothelioma. The result revealed significantly higher
64
hypermethylated genes in ovarian cancer include but are concentrations of FOLR1 and FOLR3 in ovarian cancer
not limited to DAPK, TMS1/ASC, BRCA1, p16, ICAM-1, samples compared to other samples. 79

Volume 4 Issue 1 (2025) 20 doi: 10.36922/td.5369