Kldiashvili Ekaterina, Abiatari Ivane, Kekelia Elene, Iordanishvili Saba, Metreveli Tornike, Dumbadze Eter
Petre Shotadze Tbilisi Medical Academy, Ketevan Tsamebuli avenue 51/2, Tbilisi, Georgia.
Institute of Medical and Public Health Research, Ilia State University, Ilia Chavchavadze Avenue 32, Tbilisi, Georgia.
PLoS One. 2025 Jul 17;20(7):e0328557. doi: 10.1371/journal.pone.0328557. eCollection 2025.
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.
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.
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.
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.
SOX2、PIWI蛋白和MALAT1是与癌症进展、增殖及上皮-间质转化（EMT）相关的分子调节因子。本研究评估了它们在结直肠癌、乳腺癌和前列腺癌患者血浆样本中的表达，并评估了它们与标准免疫组织化学（IHC）标志物的相关性。
共招募300名参与者：150例经组织学确诊的癌症患者（50例结直肠癌、50例乳腺癌和50例前列腺癌病例）以及150名年龄和性别匹配的健康对照者。分别通过定量实时聚合酶链反应（qRT-PCR）和酶联免疫吸附测定（ELISA）测量SOX2、PIWIL1、PIWIL2和MALAT1的血浆RNA和蛋白质水平。从临床记录中获取IHC评分（Ki-67、p53、E-钙黏蛋白、波形蛋白、雌激素受体/孕激素受体、人表皮生长因子受体2、雄激素受体）。采用受试者工作特征曲线（ROC）分析、多变量逻辑回归（校正年龄和性别）以及Pearson相关系数来评估生物标志物的诊断性能和肿瘤标志物关联。
与对照组相比，癌症患者的SOX2、PIWI蛋白和MALAT1显著升高（p < 0.001），qRT-PCR和ELISA结果高度相关。所有这三种生物标志物均与Ki-67呈强正相关（r = 0.65 - 0.72，p < 0.001），并且MALAT1与EMT标志物变化相关（E-钙黏蛋白降低，波形蛋白升高；p < 0.001）。校正后的ROC分析得出单个生物标志物的曲线下面积（AUC）值为0.82 - 0.89，敏感性范围为72% - 84%，特异性范围为75% - 87%。在结直肠癌和乳腺癌组织中，SOX2水平与Ki-67和p53 IHC阳性呈显著相关（p < 0.01），尽管p53染色的功能意义仍不明确。
癌症患者与健康对照者之间SOX2、PIWI蛋白和MALAT1的差异表达支持了它们作为区分癌症病例与非癌症病例的血浆生物标志物的潜在效用。这些发现支持了它们作为区分癌症患者与健康个体的非侵入性生物标志物的潜在效用。
