Phosphorylated signal transducer and activator of transcription proteins 1 in salivary glandular tissue: an important histological marker for diagnosis of primary Sjögren's syndrome

Abstract

Objectives The pathological diagnostic criteria for primary Sjögren's syndrome (SjS) have certain limitations. We first explored the key pathogenic pathways of SjS through a bioinformatics approach, and then evaluated the diagnostic value of the important biomarker in SjS. Methods Transcriptome data from non-SjS controls and patients with SjS were analysed using integrated bioinformatics methods. In a case-control study, phosphorylated signal transducer and activator of transcription proteins 1 (p-STAT1), a key biomarker for the activation of interferon (IFN) pathway, was selected to evaluate its diagnostic value by immunohistochemical analyses in salivary gland (SG) tissues. Results The IFN-related pathways were aberrantly activated in patients with SjS. Positive staining of p-STAT1 was detected in the SjS group, but not in non-SjS control group. There was a significant difference in the integrated optical density values of p-STAT1 expressions between the controls and the SjS groups, as well as between the controls and the SjS lymphatic foci-negative groups (p<0.05). The area under the curve of the receiver operating characteristic curve for p-STAT1 was 0.990 (95% CI 0.969 to 1.000). There was a significant difference in both accuracy and sensitivity of p-STAT1 compared with the Focus Score (p<0.05). The Jorden index for p-STAT1 was 0.968 (95% CI 0.586 to 0.999). Conclusions The IFN pathway is the key pathogenic pathway in SjS. p-STAT1 may serve as an important biomarker, in addition to lymphocytic infiltration, to diagnose SjS. Particularly in SG samples with negative lymphatic foci, p-STAT1 confers pathological diagnostic value.