Issue: Vojnosanit Pregl 2017; Vol. 74 (No. 5)

Differential gene expression in patients with anal fistula reveals high levels of prolactin receptor

Authors:
Yi-huan Song, Jian-ming Qiu, Guan-gen Yang, Dong Wang, A-li Lin, Kan Xu

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Background/Aim. There are limited data examining varia-tions in the local expression of inflammatory mediators in anal fistulas where it is anticipated that an improved under-standing of the inflammatory milieu might lead to the poten-tial therapeutic option of instillation therapy in complicated cases. The aim of the present study was to examine prolactin receptors (PRLR) as inflammatory markers and to correlate their expression with both the complexity of anal fistulas and the likelihood of fistula recurrence. Methods. Microarray was used to screen the differentially expressed gene profile of anal fistula using anal mucosa samples with hemorrhoids with age- and sex-matched patients as controls and then a prospective analysis of 65 patients was conducted with anal fistulas. PRLR immunohistochemistry was performed to define expression in simple, complex and recurrent anal fistula cases. The quantita-tive image comparison was performed combining staining in-tensity with cellular distribution in order to create high and low score PRLR immunohistochemical groupings. Results. A dif-ferential expression profile of 190 genes was found. PRLR ex-pression was 2.91 times lower in anal fistula compared with control. Sixty-five patients were assessed (35 simple, 30 com-plex cases). Simple fistulas showed significantly higher PRLR expression than complex cases with recurrent fistulae showing overall lower PRLR expression than de novo cases (p = 0.001). These findings were reflected in measurable integrated optical density for complex and recurrent cases (complex cases, 8.31 ± 4.91  104 vs simple cases, 12.30 ± 6.91  104; p < 0.01; recur-rent cases, 7.21 ± 3.51  104 vs primarily healing cases, 8.31 ± 4.91  104; p < 0.05). In univariate regression analysis, low PRLR expression correlated with fistula complexity; a signifi-cant independent effect maintained in multivariate analysis odds ratio [(OR) low to high PRLR expression = 9.52; p = 0.001)]. Conclusion. PRLR expression inversely correlates with anal fistula complexity. Further work must define the spe-cificity of this finding and its relationship to other conventional mediators of inflammation.