高iNOS和IL-1β免疫反应是结肠炎相关结直肠癌肿瘤的特征,但不能预测5年生存率。

IF 1.5 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Upsala journal of medical sciences Pub Date : 2024-01-02 eCollection Date: 2023-01-01 DOI:10.48101/ujms.v128.10241
Kajsa Björner, Wei-Na Chen, Venkata Ram Gannavarapu, Fredrik Axling, Miklos Gulyas, Mohammad Abdul Halim, Dominic-Luc Webb, Per M Hellström
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引用次数: 0

摘要

背景:炎症性肠病(IBD,主要是溃疡性结肠炎和克罗恩病)与结直肠癌(CRC)的发生有关,被称为结肠炎相关性结直肠癌(CAC)。在 IBD 炎症发作时,由于炎症组织中的诱导型一氧化氮合酶(iNOS)活性增加,管腔一氧化氮(NO)的产生也随之增加。据认为,iNOS 与促炎症的白细胞介素-1β(IL-1β)相似。目的:本研究的主要目的是研究 iNOS 和 IL-1β 在 CAC 肿瘤中的免疫反应,并与 CRC 和正常结肠粘膜进行比较;次要目的是确定免疫反应是否与 CAC 的 5 年生存率相关:方法:对以下组织切片进行免疫组化:方法:对以下组织切片进行免疫组化:CAC(n = 59);散发性 CRC(sCRC)(n = 12);sCRC 边缘外大于 2 厘米的结肠粘膜(正常粘膜)(n = 22);癌旁 IBD(pIBD)(n = 12)。iNOS和IL-1β的表达分别在上皮和基质中量化。数据采用 Mann-Whitney U 检验和 5 年 Kaplan-Meier 生存曲线的 log-rank 检验进行评估。结果与在线 mRNA 数据库进行了比较:结果:免疫反应主要发生在上皮细胞,其次是基质。与正常粘膜相比,CAC上皮细胞中iNOS(P < 0.01)和IL-1β(P < 0.005)的免疫反应性更高。在CAC基质中,iNOS的免疫oreactivity低于正常粘膜(P < 0.001),而IL-1β则高于正常粘膜(P < 0.05)。CAC患者的iNOS或IL-1β免疫活性差异与5年生存率无关。这些发现得到了在线 mRNA 数据库的支持:结论:与 IBD 中产生大量 NO 的情况一致,CAC 上皮细胞中有更多的 iNOS,但基质中没有。上皮细胞和基质中的 IL-1β 也存在这种免疫反应差异。精氨酸或 iNOS 活性对 CAC 化疗的干预并不直接。
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High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.

Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown.

Aim: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC.

Methods: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases.

Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases.

Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.

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来源期刊
Upsala journal of medical sciences
Upsala journal of medical sciences 医学-医学:内科
CiteScore
5.60
自引率
0.00%
发文量
31
审稿时长
6-12 weeks
期刊介绍: Upsala Journal of Medical Sciences is published for the Upsala Medical Society. It has been published since 1865 and is one of the oldest medical journals in Sweden. The journal publishes clinical and experimental original works in the medical field. Although focusing on regional issues, the journal always welcomes contributions from outside Sweden. Specially extended issues are published occasionally, dealing with special topics, congress proceedings and academic dissertations.
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