胃肿瘤中 IDO1 介导的色氨酸分解：它在组织病理学、分化和转移轴中的潜在作用。

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-10-16 DOI:10.1016/j.prp.2024.155655

Cem Horozoglu , Mehmet Tolgahan Hakan , Dilara Sonmez , Asli Yildiz , Seyda Demirkol , Fikret Aktas , Sidar Bagbudar , Ozlem Kucukhuseyin , Soykan Arikan , Filiz Akyuz , Ilhan Yaylim

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引用次数: 0

摘要

背景：吲哚胺2,3-二氧化酶1（IDO1）介导的色氨酸降解是色氨酸/犬尿氨酸通路的限速酶，可能会导致肿瘤微环境中的免疫抑制，同时增强肿瘤病灶的增殖和转移活性、IDO1 抑制剂的阶段性研究正在进行中，我们的研究旨在以临床病理学为轴心，评估 IDO1 基因表达对胃癌（GC）肿瘤和肿瘤微环境病灶中色氨酸/犬尿氨酸通路的潜在贡献：采用病例对照研究设计，使用高压液相色谱-荧光检测器（HPLC-FD）测定 51 例胃癌患者和 49 例健康对照者血清中的色氨酸及其代谢物。采用定量 PCR（q-PCR）技术检测了 102 例肿瘤组织和肿瘤微环境中 IDO1 的表达情况：结果发现：在胃肿瘤中，IDO1的表达量随肿瘤微环境的变化而降低3.25倍（p=0.05），在标志环细胞癌（SRCC）和无远处器官转移的分化不良肿瘤中，IDO1的表达量高出2倍多（p=0.05）。

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IDO1-mediated catabolism of tryptophan in gastric tumors: Its potential role in the axis of histopathology, differentiation and metastasis

Background

Indoleamine 2,3-Dioxygenase 1 (IDO1)-mediated tryptophan degradation, which is the rate-limiting enzyme of tryptophan/kynurenine pathway, may cause immune suppression in the tumor microenvironment, while potentiating proliferative and metastatic activity in the tumor focus, Phase studies of IDO1 inhibitors are ongoing, and our study aims to evaluate the potential contribution of IDO1 gene expression to the tryptophan/kynurenine pathway in tumor and tumor microenvironment foci in gastric cancer (GC) on a clinicopathological axis,

Method

In the case-control study design, the determination of tryptophan and its metabolites in the serum of 51 GC and 49 healthy controls was made using High Pressure Liquid Chromatography-Fluorescence Detector (HPLC-FD). IDO1 expression in a total of 102 tissues with tumor and tumor microenvironment was detected by quantitative PCR (q-PCR).

Results

In gastric tumors, 3,25-fold decreased expression of IDO1 was detected according to the tumor microenvironment (p=0,05), IDO1 expression was found to be more than 2 times higher in signet ring cell carcinoma (SRCC) and poorly differentiated tumors without distant organ metastasis (p<0,05), In GC, tryptophan level was found to be 1,6 times lower than in control (AUC:0889; cut off≤21,57; p<0001), Low tryptophan level was found in advanced tumor stage compared to early stage and in the presence of perineural invasion compared to its absence (p<0,05) The level of kynurenine was found to be approximately 1,8 times lower in SRCC (p=0,04),

Conclusion

Increased tryptophan accumulation in the gastric tumor and its microenvironment, when catabolized via IDO1, exhibits histological type, tumor differentiation, and metastasis-promoting effects more prominently in aggressive subtypes such as SRCC,

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.