PO.TB09.03 · 肿瘤生物学
前列腺素E₂信号在溃疡性结肠炎癌变中的意义
Significance of prostaglandin E₂ signaling in the carcinogenesis of ulcerative colitis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：随着溃疡性结肠炎（UC）患病率的上升，在长期炎症性肠病（IBD）背景下发生的结直肠癌发病率一直在增加。与普通人群相比，长期UC患者发生结直肠癌（CRC）的风险约高五倍。然而，UC相关癌变背后的分子机制仍未明确界定。前列腺素E₂（PGE₂）信号是炎症的关键介质之一，在UC患者的炎症结肠组织中已观察到PGE₂水平升高。PGE₂信号还在多种癌症类型中促进肿瘤增殖和转移。
目的：通过检测PGE₂受体EP2和EP4在UC相关肿瘤性病变中的表达，阐明PGE₂信号在UC相关癌变中的参与作用。
方法：纳入41例在本机构接受UC相关肿瘤（16例异型增生、25例癌）手术的患者。对异型增生和癌性病变的石蜡包埋切片进行EP2和EP4的免疫组化染色。对EP2/EP4的表达强度和阳性比例进行评分，并分析EP2/EP4受体表达与临床病理参数之间的相关性。
结果：在UC相关肿瘤中，癌组织的EP2和EP4表达高于异型增生组织。任一受体（EP2或EP4）的表达在癌性病变中（81.5%，22/27）比异型增生病变（50.0%，7/14）更为常见（p = 0.0678）。EP2阳性见于66.7%的癌性病变（18/27）和42.9%的异型增生病变（6/14）（p = 0.189）。EP4表达在癌性病变中（63.0%，17/27）有高于异型增生病变（28.6%，4/14）的趋势（p = 0.0516），而EP2阳性则无此趋势（p = 0.189；见于66.7%的癌性病变[18/27]和42.9%的异型增生病变[6/14]）（p = 0.189）。任一受体（EP2或EP4）的表达在癌性病变中（81.5%，22/27）比异型增生病变（50.0%，7/14）更为常见（p = 0.0678）。相比之下，EP2或EP4受体表达与癌症肿瘤分期、浸润深度或预后无显著相关。
结论：这些发现提示，PGE₂信号，尤其是通过EP4受体，可能参与溃疡性结肠炎（UC）的癌变过程。EP4介导的通路可能成为UC相关结直肠癌（CRC）潜在的治疗或预防靶点。
查看英文原文 English abstract
Background The incidence of colorectal cancer arising in the setting of long-standing inflammatory bowel disease (IBD) has been increasing with the rising prevalence of ulcerative colitis (UC). Patients with long-standing UC have an approximately five-fold higher risk of colorectal cancer (CRC) compared with the general population. However, the molecular mechanisms underlying UC-associated carcinogenesis remain poorly defined. Prostaglandin E₂ (PGE₂) signaling is one of a key mediators of inflammation, and elevated PGE₂ levels have been observed in inflamed colonic tissue of UC patients. PGE₂ signaling also promotes tumor proliferation and metastasis in several cancer types.
Objective To clarify the involvement of PGE₂ signaling in UC-associated carcinogenesis by examining the expression of PGE₂ receptors EP2 and EP4 in UC-related neoplastic lesions.
Methods Forty-one patients who underwent the surgical operation for UC-associated neoplasia (16 dysplasia, 25 carcinoma) at our institution were included. Paraffin-embedded sections of dysplastic and cancerous lesions were subjected to immunohistochemical staining for EP2 and EP4. Expression intensity and proportion of EP2/EP4 were scored, and correlations between EP2/EP4receptor expression and clinicopathological parameters were analyzed.
Results Cancer tissues showed higher expression of EP2 and EP4 than dysplastic tissues in UC-associated neoplasia. Expression of either receptor (EP2 or EP4) was more frequent (p = 0.0678) in cancer lesions (81.5%, 22/27) compared with dysplastic lesions (50.0%, 7/14). EP2 positivity was observed in 66.7% of cancer lesions (18/27) and 42.9% of dysplastic lesions (6/14) (p = 0.189). EP4 expression tended to be higher (p = 0.0516) in cancer lesions (63.0%, 17/27) than in dysplastic lesions (28.6%, 4/14) (p = 0.0516) while EP2 positivity was not (p = 0.189;observed in 66.7% of cancer lesions (18/27) and 42.9% of dysplastic lesions) (6/14) (p = 0.189). Expression of either receptor (EP2 or EP4) was more frequent in cancer lesions (81.5%, 22/27) compared with dysplastic lesions (50.0%, 7/14) (p = 0.0678). In contrast, EP2 or EP4 Receptor expression was not significantly associated with cancer tumor stage, depth of invasion, or prognosis.
Conclusion These findings suggest that PGE₂ signaling, particularly through the EP4 receptor, may might contribute to the carcinogenesis in UC ulcerative colitis. EP4-mediated pathways may represent potential therapeutic or preventive targets in UC-associated CRC colorectal cancer.
利益披露 Disclosure
T. Fukuoka, None..
M. Yashiro, None..
H. Kasashima, None..
N. Naito, None..
I. Omori, None..
Y. Fukui, None..
Y. Seki, None..
K. Kuroda, None..
Y. Miki, None..
M. Yoshii, None..
T. Tamura, None..
M. Shibutani, None..
T. Toyokawa, None..
K. Maeda, None.