Dr Henry D Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Inflamm Bowel Dis. 2013 Feb;19(2):275-82. doi: 10.1097/MIB.0b013e318286ff2e.
The expression and distribution of farnesoid X receptor (FXR) in colitis and colitis-associated neoplasia (CAN) is unknown. We investigated FXR expression in neoplastic and nonneoplastic tissue from ulcerative colitis (UC) patients, with or without primary sclerosing cholangitis (PSC), as well as the role of DNA methylation in FXR expression in colorectal cancer (CRC) cell lines.
Samples from the right (RC) and left (LC) colon of patients with UC, with and without PSC, and with or without CAN, were stained by immunohistochemistry and scored semiquantitatively for nuclear FXR expression. FXR expression was analyzed by western blot and polymerase chain reaction (PCR) in nine different CRC cell lines before and after demethylation with 5-azacytidine.
In nondysplastic samples, FXR expression demonstrated a diminishing expression from proximal to distal colon (strong FXR expression: 39% RC samples vs. 14% LC samples; P = 0.007). With moderate-to-severe inflammation, FXR expression was almost always absent or weak in both UC and PSC-UC, regardless of location. With quiescent/mild inflammation, 56% of UC samples in the RC retained strong FXR expression versus 24% of PSC-UC samples (P= 0.017). FXR was absent in 72% of the neoplastic samples, with an inverse association with the grade of dysplasia. FXR expression was absent in all CRC cell lines, in some cases due to DNA methylation.
FXR expression is inversely correlated with neoplastic progression and severity of inflammation in UC. Patients with PSC-UC have diminished FXR expression in the proximal colon compared to UC patients. This finding could contribute to the higher risk of proximal neoplasia in PSC patients.
法尼醇 X 受体（FXR）在结肠炎和结肠炎相关肿瘤（CAN）中的表达和分布尚不清楚。我们研究了溃疡性结肠炎（UC）患者的肿瘤和非肿瘤组织中 FXR 的表达，这些患者伴有或不伴有原发性硬化性胆管炎（PSC），以及 DNA 甲基化在结直肠癌（CRC）细胞系中对 FXR 表达的作用。
对伴有或不伴有 PSC 和 CAN 的 UC 患者的右（RC）和左（LC）结肠组织进行免疫组织化学染色，并对核 FXR 表达进行半定量评分。在经过 5-氮杂胞苷去甲基化处理前后，用 Western blot 和聚合酶链反应（PCR）分析 9 种不同 CRC 细胞系中的 FXR 表达。
在非发育不良样本中，FXR 表达表现为从近端到远端结肠的表达逐渐减少（强 FXR 表达：39% RC 样本比 14% LC 样本；P = 0.007）。在 UC 和 PSC-UC 中，随着炎症从中等到严重，无论位置如何，FXR 表达几乎总是不存在或微弱。在静止/轻度炎症时，RC 中 56%的 UC 样本保留强 FXR 表达，而 PSC-UC 样本中仅有 24%（P = 0.017）。72%的肿瘤样本中 FXR 表达缺失，与异型增生的程度呈反比。所有 CRC 细胞系中均不存在 FXR 表达，在某些情况下是由于 DNA 甲基化。
FXR 的表达与 UC 中的肿瘤进展和炎症严重程度呈负相关。与 UC 患者相比，PSC-UC 患者的近端结肠 FXR 表达减少。这一发现可能导致 PSC 患者近端肿瘤的风险增加。
