Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressive behavior in colorectal cancer

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Abstract Colorectal carcinoma (CRC) represents a health issue causing significant morbidity and mortality worldwide. Further biomarkers are needed to allow patient risk stratification in terms of prognosis. In this study, we aimed to clarify 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) analyzing a cohort of 285 patients with surgically treated CRC, analyzing quantitative associations of all three markers and several traditional prognosticators (tumor stage, histological grade, variant morphology, laterality, mismatch-repair/MMR status). The results of the study include negative significant prognostic impact of loss of SATB2 expression in 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 significant detrimental impact in case of stronger expression. Loss of SATB2 was associated with CK7 expression, advanced tumor stage, high grade, right-sided localization, and borderline insignificantly with PD-L1 expression. CK7 expression was associated with high grade. Both loss of SATB2 and CK7 expression were significant negative prognostic predictors in the multivariate analysis adjusting on associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and PD-L1 expression characterize aggressive phenotype of CRC.

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