Faculty of Medicine, Halic University, Istanbul, Turkey.
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Pathol Res Pract. 2024 Nov;263:155655. doi: 10.1016/j.prp.2024.155655. Epub 2024 Oct 16.
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).
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.
吲哚胺 2,3-双加氧酶 1（IDO1）介导的色氨酸降解是色氨酸/犬尿氨酸途径的限速酶，可能导致肿瘤微环境中的免疫抑制，同时增强肿瘤病灶中的增殖和转移活性。IDO1 抑制剂的阶段研究正在进行中，我们的研究旨在评估 IDO1 基因表达对胃癌（GC）肿瘤和肿瘤微环境病灶中色氨酸/犬尿氨酸途径的潜在贡献，方法：在病例对照研究设计中，使用高效液相色谱-荧光检测器（HPLC-FD）测定 51 例 GC 和 49 例健康对照者血清中的色氨酸及其代谢物。通过定量 PCR（q-PCR）检测总共 102 个组织中肿瘤和肿瘤微环境中的 IDO1 表达。
根据肿瘤微环境，在胃肿瘤中检测到 IDO1 的表达降低了 3.25 倍（p=0.05）。在印戒细胞癌（SRCC）和无远处器官转移的低分化肿瘤中，发现 IDO1 表达高出 2 倍以上（p<0.05）。在 GC 中，色氨酸水平比对照组低 1.6 倍（AUC：0889；cut off≤21.57；p<0.001）。与早期阶段相比，晚期肿瘤阶段和存在神经周围侵犯的情况下，色氨酸水平较低（p<0.05）。与 SRCC 相比，发现犬尿氨酸水平低约 1.8 倍（p=0.04）。
在 GC 中，当 IDO1 代谢时，在胃肿瘤及其微环境中积累的色氨酸增加，在侵袭性亚型如 SRCC 中表现出组织学类型、肿瘤分化和促进转移的作用更为明显。
