Diagnostic efficacy of the new prospective biomarker’s combination CA 15-3 and CA-62 for early-stage breast cancer detection: Results of the blind prospective-retrospective clinical study

Abstract

BACKGROUND: Combination of different cancer markers is often used for predicting tumor growth, for the response to cancer therapy, and for increase in the positive diagnosis ratio in the malignant tumors. OBJECTIVE: Evaluation of the diagnostic efficacy of CA 15-3 and CA-62 cancer markers combination for early stages of breast cancer (BC) detection. METHODS: This retrospective blind study was performed on 2 clinically validated Sets that included serum measurements of CA 15-3 ELISA and CLIA-CA-62 assays in 488 serum samples with TNM classification. A study included 300 BC patients (254 at Stages I and II, 20 with ductal carcinoma in situ (DCIS), and 26 Stages III and IV patients), 47 patients with breast benign diseases, and 141 healthy controls. RESULTS: Sensitivity for DCIS & Stage I breast cancer detection was 75% at 100% Specificity (AUC = 0.895) using a following combination of two antigens: 10 < CA15-3 < 46 U/ml and CA-62 ⩾ 6300 U/ml, which allows eliminating false positive results. CONCLUSIONS: The results obtained in a blind study demonstrate that a combination of CA15-3 with CA-62 yields 75% Sensitivity at 100% Specificity for DCIS and Stage I breast cancer detection, which has a potential to be integrated into existing screening programs.

Potential clinical application of the cancer antigen CA‑62 for differential diagnosis of prostate cancer and benign prostatic hyperplasia at the elevated prostate‑specific antigen

“…На клеточной мембране таких низкодифференцированных мезенхимальных стволовых клеток с самого начала канцерогенеза в больших количествах образуется сильно гликозилированный гликопротеин СА-62, который попадает в кровь с поверхности клеток на самых ранних стадиях рака, включая карциномы in situ, и детектируется при помощи ИХА-СА-62 хемилюминесцентного иммуноанализа. Более ранние исследования показали, что злокачественные клетки демонстрируют значительную экспрессию гликопротеина СА-62 во всех изученных эпителиальных карциномах различных локализаций, таких как молочная железа, простата, легкие, желудок, кишка и яичники [14][15][16]. Однако, несмотря на проявление маркера СА-62 в различных злокачественных новообразованиях эпителиального генеза, он обладает онкоспецифичностью (более 90 %) при сравнении злокачественных новообразований с доброкачественными заболеваниями и данными условно здоровых субъектов.…”

“…med.). 2023; 10(1): [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. https://doi.org/10.17709/2410-1893-2023-10-1-1, EDN: JVPCQC Research and Practical Medicine Journal.…”

Clinical validation of the novel CLIA-CA-62 assay efficacy for early-stage breast cancer detection

“…Authors ( 16 , 17 ) revealed that a CA-62 marker associated with epithelial tumors can be significantly expressed and detected to varying degrees in the tissues of malignant tumors (such as breast, prostate, lung, uterus, stomach, kidney, colon, and ovaries), as well as in various human biological fluids (including blood and saliva). At the same time, healthy control subjects do not demonstrate increased expression of the CA-62 marker.…”

“…Tumor cells release into the blood two main soluble cytoplasmic fractions of N-glycoprotein that are detected by the antibody used in the test. This allows to quantitatively measure a serum level of CA-62 antigen using a specific chemiluminescent assay CLIA-CA-62 intended to help with the medical decision-making process and recommended for early cancer detection in combination with clinical data and other diagnostic procedures ( 16 , 17 ).…”

“…Human CLIA-CA-62 immunoassay is based on the novel marker for epithelial carcinomas CA-62, which is a carcinoma-specific mesenchymal marker, expressed on the epithelial cell surface of the EMT-transformed undifferentiated stem cells from the onset of cancer development. There are some previous publications describing CA-62, a patented set of reagents CLIA-CA-62 based on the biomarker CA-62 for early cancer detection (16)(17)(18) and monitoring response to chemotherapy (19). A marker for epithelial carcinomas CA-62 represents a family of low-weight membrane transport N-glycoproteins that bind alpha-fetoprotein (AFP) using a special combination of the branched polysaccharides, which are located on the mesenchymal cells' surface and function by Clathrin-mediated endocytosis.…”