# SOX2, PIWI proteins, and MALAT1 – plasma-based emerging biomarkers for cancer detection and monitoring

**Authors:** Ekaterina Kldiashvili, Ivane Abiatari, Elene Kekelia, Saba Iordanishvili, Tornike Metreveli, Eter Dumbadze

PMC · DOI: 10.1371/journal.pone.0328557 · PLOS One · 2025-07-17

## TL;DR

This study explores SOX2, PIWI proteins, and MALAT1 as potential non-invasive blood-based biomarkers for detecting and monitoring colorectal, breast, and prostate cancers.

## Contribution

The study identifies plasma-based expression of SOX2, PIWI proteins, and MALAT1 as novel potential biomarkers for cancer detection and monitoring.

## Key findings

- SOX2, PIWI proteins, and MALAT1 were significantly elevated in cancer patients compared to healthy controls.
- These biomarkers showed strong correlations with Ki-67 and EMT markers, suggesting a role in cancer progression.
- Adjusted ROC analysis showed AUC values of 0.82–0.89, indicating good diagnostic potential.

## Abstract

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.

## Linked entities

- **Genes:** SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657], PIWIL1 (piwi like RNA-mediated gene silencing 1) [NCBI Gene 9271], PIWIL2 (piwi like RNA-mediated gene silencing 2) [NCBI Gene 55124], MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938], Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345], TP53 (tumor protein p53) [NCBI Gene 7157], shg (shotgun) [NCBI Gene 37386], PRELID1 (PRELI domain containing 1) [NCBI Gene 737446]
- **Diseases:** colorectal cancer (MONDO:0005575), breast cancer (MONDO:0004989), prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, PIWIL1 (piwi like RNA-mediated gene silencing 1) [NCBI Gene 9271] {aka CT80.1, HIWI, MIWI, PIWI}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, VIM (vimentin) [NCBI Gene 7431], PIWIL2 (piwi like RNA-mediated gene silencing 2) [NCBI Gene 55124] {aka CT80, HILI, PIWIL1L, mili}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}
- **Diseases:** prostate cancer (MESH:D011471), colorectal cancer (MESH:D015179), cancer (MESH:D009369), breast cancer (MESH:D001943)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12270145/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12270145/full.md

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Source: https://tomesphere.com/paper/PMC12270145