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TOX 表达随着结直肠癌的进展而降低,并且与 CD4 T 细胞密度和具核梭杆菌感染有关。

TOX expression decreases with progression of colorectal cancers and is associated with CD4 T-cell density and Fusobacterium nucleatum infection.

机构信息

Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China 646000.

Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Sichuan, China 646000.

出版信息

Hum Pathol. 2018 Sep;79:93-101. doi: 10.1016/j.humpath.2018.05.008. Epub 2018 May 21.

DOI:10.1016/j.humpath.2018.05.008
PMID:29792893
Abstract

Fusobacterium nucleatum in the tumor microenvironment plays an important role in the development of colorectal cancer. The underlying mechanism of action, however, remains to be elucidated. We evaluated the relation of F nucleatum amount to thymocyte selection-associated high-mobility group box (TOX) protein expression and CD4 T-cell density in 138 human colorectal tissues. TOX expression and CD4 T-cell density in Fnucleatum-negative tissues were significantly higher compared to those in Fnucleatum-positive tissues (P < .001 and P = .002, respectively). We found a negative correlation between F nucleatum abundance and TOX expression (P < .001) and CD4 T-cell density (P < .001). TOX expression in normal mucosa, hyperplastic polyps, and adenomas was significantly higher than in sessile serrated adenomas and different stages of carcinomas (P < .05). Moreover, CD4 T-cell density in high-TOX expression tissues was significantly higher than in low-TOX expression tissues (P = .003). A positive correlation was found between TOX expression and CD4 T-cell density in colorectal tissues (Spearman correlation coefficient: 0.362, 95% confidence interval: 0.051-0.641, P = .022). Our findings suggest that F nucleatum may suppress antitumor immune responses by decreasing CD4 T-cell density and TOX expression in the progression of colorectal cancer.

摘要

具核梭杆菌在肿瘤微环境中在结直肠癌的发展中起重要作用。然而,其作用机制仍有待阐明。我们评估了 138 个人结直肠组织中 F 核梭杆菌数量与胸腺细胞选择相关的高迁移率族蛋白(TOX)蛋白表达和 CD4 T 细胞密度的关系。Fnucleatum 阴性组织中的 TOX 表达和 CD4 T 细胞密度明显高于 Fnucleatum 阳性组织(P <.001 和 P =.002)。我们发现 F 核梭杆菌丰度与 TOX 表达(P <.001)和 CD4 T 细胞密度(P <.001)呈负相关。正常黏膜、增生性息肉和腺瘤中的 TOX 表达明显高于无蒂锯齿状腺瘤和不同阶段的癌(P <.05)。此外,高 TOX 表达组织中的 CD4 T 细胞密度明显高于低 TOX 表达组织(P =.003)。结直肠组织中 TOX 表达与 CD4 T 细胞密度之间存在正相关(Spearman 相关系数:0.362,95%置信区间:0.051-0.641,P =.022)。我们的研究结果表明,F 核梭杆菌可能通过降低结直肠癌进展过程中的 CD4 T 细胞密度和 TOX 表达来抑制抗肿瘤免疫反应。

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