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SOX2, PIWI proteins, and MALAT1 - plasma-based emerging biomarkers for cancer detection and monitoring
Ekaterina Kldiashvili1, Ivane Abiatari2, Elene Kekelia1
1Petre Shotadze Tbilisi Medical Academy, Ketevan Tsamebuli avenue 51/2, Tbilisi, Georgia.
Background:
SOX2, PIWI proteins, and MALAT1 are molecular regulators implicated in cancer progression, proliferation, and epithelial-mesenchmal transition (EMT). This study evaluated their expression in plasma samples from patients with colorectal, breast, and prostate cancers, and assessed their correlations with standard immunohistochemical (IHC) markers.
Methods:
A total 300 participants were enrolled: 150 patients with histologically confirmed cancers (50 colorectal cancer, 50 breast cancer, and 50 prostate cancer cases) and 150 age- and sex-matched healthy controls. Plasma RNA and protein levels of SOX2, PIWIL1, PIWIL2, and MALAT1 were measured via quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. IHC scores (Ki-67, p53, E-cadherin, vimentin, estrogen receptor/progesterone receptor, human epidermal growth factor receptor 2, androgen receptor) were retrieved from clinical records. Receiver-operating characteristic curve (ROC) analysis, multivariable logistic regression (adjusting for age and sex), and Pearson's correlation coefficients were used to evaluate biomarker diagnostic performance and tumor marker associations.
Results:
SOX2, PIWI proteins, and MALAT1 were significantly elevated in cancer patients versus controls (p < 0.001), with qRT-PCR and ELISA results strongly correlated. All three biomarkers showed strong positive correlations with Ki-67 (r = 0.65-0.72, p < 0.001), and MALAT1 was associated with EMT marker changes (↓E-cadherin, ↑ vimentin; p < 0.001). Adjusted ROC analysis yielded area under the curve (AUC) values of 0.82-0.89 for individual biomarkers, with sensitivity ranging from 72-84% and specificity from 75-87%. SOX2 levels showed significant correlations with Ki-67 and p53 IHC positivity in colorectal and breast cancer tissues (p < 0.01), although the functional significance of p53 staining remains inconclusive.
Conclusion:
The differential expression of SOX2, PIWI proteins, and MALAT1 between cancer patients and healthy controls supports their potential utility as plasma-based biomarkers for distinguishing cancer cases from non-cancer cases. These findings support their potential utility as non-invasive biomarkers for distinguishing cancer cases from healthy individuals.
