UNASSIGNED: The relationship of exostosin 1 and exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial.
UNASSIGNED: EXT1/EXT2 was performed by immunohistochemistry (IHC) in 283 consecutive patients with MLN. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients. The primary end points were adverse renal events, including death, dialysis, and renal transplantation.
UNASSIGNED: Of the patients with MLN, 29.3% were positive for EXT1/EXT2. The prevalence of EXT1/2-positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P < 0.001). For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter (6 [interquartile range, IQR: 2-25] months vs. 12 [IQR: 3-49] months, P = 0.008 and 3 [IQR: 2-18] months vs. 6 [IQR: 2-23] months, P = 0.039) and they had significantly lower systemic lupus erythematosus Disease Activity Index (SLEDAI) scores (P = 0.015) and lower serum creatinine levels (P < 0.001), higher hemoglobin (P = 0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P < 0.001; interstitial fibrosis, P = 0.006; and tubular atrophy, P = 0.002) and fewer activity indicators (endocapillary hypercellularity, P = 0.012; cellular crescents, P = 0.007; and fibrocellular crescents, P < 0.001) on renal biopsy. After a median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P = 0.001).
UNASSIGNED: Compared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index.

OBJECTIVE: The exostosins (EXT), which are responsible for heparan sulfate backbone synthesis and play a vital role in tissue homeostasis, have been reported to be correlated with prognosis of various cancers. However, the expression, prognostic value, and immune infiltration of EXT1 and EXT2 in head and neck squamous cell carcinoma (HNSC) remain uncertain.
METHODS: GEPIA, UALCAN, and Xiantao bioinformatics tools were used to explore the EXT1 and EXT2 expression level in HNSC. GEPIA and Sangerbox were utilised to obtain the prognostic value of EXT1 and EXT2 in HNSC. Genetic alterations, immune cell infiltration, and single-cell analysis were conducted in cBioPortal, TIMER, and TISCH2. In addition, the expressions of EXT1 and EXT2 were validated by real-time polymerase chain reaction (PCR) in HNSC samples.
RESULTS: EXT1 and EXT2 were highly expressed in HNSC, especially in malignant cells. Only EXT2 was significantly negatively correlated to the prognosis of patients with HNSC. EXT1 and EXT2 were found to be associated with focal adhesin and cell adhesin molecule binding. EXT1 expression levels were considerably connected with CD8+ T cell infiltrating levels, whilst EXT2 expression levels were considerably negatively connected with infiltrating levels of CD4+ T cells, macrophages, neutrophils, and dendritic cells in HNSC. The gene mutation rates of EXT1 and EXT2 in HNSC were 7% and 2.8%, respectively. Moreover, EXT2 was validated to be highly expressed in HNSC samples by real-time PCR.
CONCLUSIONS: EXT2 was highly expressed and presented negative correlation with the prognosis and immune infiltration of HNSC, which might be a potential biomarker for HNSC.

暂无摘要。

There have been only several studies on the correlation between glomerular exostosin expression and membranous lupus nephritis. In this study, we validate the previous findings in Chinese patients with class 5 lupus nephritis.
One hundred sixty-five patients with class 5 lupus nephritis and varying numbers of control patients were included. Exostosin1/exostosin2 staining was performed by immunohistochemistry, and the staining intensity was quantified using an imaging analysis system. Between-group comparisons were tested for statistical significance using the Pearson chi-squared test, the Fisher exact test, the unpaired t test, the Mann-Whitney U test, or one-way ANOVA.
In total, 46% of patients with class 5 lupus nephritis, 9% of patients with class 5 + 3/4 lupus nephritis, and none of the other classes of lupus nephritis were exostosin positive. Only three patients were exostosin positive among the 61 patients with other secondary membranous nephropathy. The exostosin-positive rate in nephrotic patients was significantly higher than that in patients without nephrotic syndrome (P<0.001), and the exostosin staining intensities of the patients with exostosin-positive class 5 were positively correlated with proteinuria (r=0.53; P<0.001). Compared with the patients with exostosin-negative cases, the patients with exostosin-positive cases had higher proteinuria levels (3.9 [interquartile range, 2.0-6.3] g/d versus 2.3 [interquartile range, 1.0-3.6] g/d; P<0.001); lower scores of activity index (1 [interquartile range, 1-2] versus 2 [interquartile range, 1-3]; P=0.001), chronicity index (1 [interquartile range, 0-2] versus 2 [interquartile range, 1-2]; P=0.02), and tubular atrophy score (0 [interquartile range, 0-1] versus 1 [interquartile range, 0-1]; P=0.008); a higher proportion of extensive subepithelial deposition (62% versus 27%; P<0.001); a similar treatment response; and comparable time to kidney end point. Among the 47 patients with class 5 who underwent repeat biopsy, 97% of those with exostosin-negative cases remained negative, whereas 44% of those with exostosin-positive cases were still positive. The rate of histologic transition in the patients with exostosin-negative class 5 was significantly higher than that in the patients with exostosin-positive class 5 (59% versus 22%; P=0.03).
Exostosin positivity occurred frequently in patients with class 5 lupus nephritis, and patients with exostosin-positive cases had more severe proteinuria and a lower rate of histologic transition than the exostosin-negative patients.