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促凝基因可能影响尿路上皮癌患者的血管生成、上皮-间充质转化、生存预后和肿瘤免疫微环境。

Procoagulant genes may affect angiogenesis, epithelial-mesenchymal transition, survival prognosis and tumor immune microenvironment in patients with urothelial carcinoma.

机构信息

Department of Urology, The First People’s Hospital of Foshan, Foshan, Guangdong, China.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

Aging (Albany NY). 2023 Jul 8;15(13):6429-6444. doi: 10.18632/aging.204860.

DOI:10.18632/aging.204860
PMID:37453055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10373971/
Abstract

Factors related to coagulation regulation are closely related to angiogenesis, epithelial-mesenchymal transition, tumor proliferation and metastasis, and tumor immune microenvironment remodeling in tumors. To date, there are no quantitative indicators of coagulation associated with urothelial cancer. We classified urothelial cancer into high coagulation and low coagulation subtypes by screening for procoagulant-related molecular features and screened out relevant genes representing the coagulation state of urothelial carcinoma. Tumors with increased procoagulant gene expression were consistently associated with higher T-staging ( < 0.001), lymph node metastasis ( < 0.001), stage ( < 0.001), and grade ( = 0.046). Furthermore, high expression of procoagulant genes predicts a worse prognosis, a higher tumor proliferation rate and increased angiogenesis within the tumor. In addition, according to cibersort algorithm, the increased expression of procoagulant gene was negatively correlated with the degree of T-lymphocyte infiltration and positively correlated with the degree of M2 macrophage infiltration. Increased expression of procoagulant genes in data sets treated with immune checkpoints also predicted worse response and worse prognosis. At the same time, the expression of procoagulant genes in bladder cancer promoted the activation of coagulation, EMT, TGF-β and WNT pathways.

摘要

与凝血调节相关的因素与肿瘤中的血管生成、上皮-间充质转化、肿瘤增殖和转移以及肿瘤免疫微环境重塑密切相关。迄今为止,与尿路上皮癌相关的凝血尚无定量指标。我们通过筛选促凝相关分子特征将尿路上皮癌分为高凝和低凝亚型,并筛选出代表尿路上皮癌凝血状态的相关基因。具有较高促凝基因表达的肿瘤始终与较高的 T 分期(<0.001)、淋巴结转移(<0.001)、分期(<0.001)和分级(=0.046)相关。此外,促凝基因的高表达预示着预后更差、肿瘤增殖率更高且肿瘤内血管生成增加。此外,根据 cibersort 算法,促凝基因表达增加与 T 淋巴细胞浸润程度呈负相关,与 M2 巨噬细胞浸润程度呈正相关。免疫检查点治疗数据集中促凝基因的高表达也预示着反应更差和预后更差。同时,膀胱癌中促凝基因的表达促进了凝血、EMT、TGF-β和 WNT 途径的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a7451f127b56/aging-15-204860-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/26db37966797/aging-15-204860-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/986a089d36d0/aging-15-204860-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a93aa195f762/aging-15-204860-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a7451f127b56/aging-15-204860-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/26db37966797/aging-15-204860-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/8881dd13cebe/aging-15-204860-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a4aef2c26c62/aging-15-204860-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/3ad0df1497bc/aging-15-204860-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/986a089d36d0/aging-15-204860-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a93aa195f762/aging-15-204860-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b41/10373971/a7451f127b56/aging-15-204860-g007.jpg

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