Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NU21J-03-00019
Agentura Pro Zdravotnický Výzkum České Republiky
21-27902S
Grantová Agentura České Republiky
VFN, 00064165
Ministerstvo Zdravotnictví Ceské Republiky
PubMed
36351995
PubMed Central
PMC9646713
DOI
10.1038/s41598-022-22685-0
PII: 10.1038/s41598-022-22685-0
Knihovny.cz E-zdroje
- 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
- Názvy látek
- antigeny CD274 MeSH
- CD274 protein, human MeSH Prohlížeč
- keratin-7 MeSH
- nádorové biomarkery MeSH
- SATB2 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
- vazebné proteiny DNA v oblastech připojení k matrix * 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.
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