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Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer
J. Hrudka, R. Matěj, A. Nikov, I. Tomyak, H. Fišerová, K. Jelínková, P. Waldauf
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Directory of Open Access Journals
od 2011
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Nature Open Access
od 2011-12-01
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od 2011-01-01
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od 2011-01-01
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- MeSH
- antigeny CD274 genetika metabolismus MeSH
- keratin-7 genetika MeSH
- kolorektální nádory * patologie MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- prognóza MeSH
- transkripční faktory genetika MeSH
- vazebné proteiny DNA v oblastech připojení k matrix * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
Citace poskytuje Crossref.org
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- $a Hrudka, Jan $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic. jan.hrudka@lf3.cuni.cz
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- $a Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
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- $a Matěj, Radoslav $u Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic $u Department of Pathology and Molecular Medicine, 3rd Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic $u Department of Pathology, 1st Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic
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