Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer.

Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer.
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DOI:
10.3748/wjg.v28.i30.4120
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发表时间:
2022-08-14
影响因子:
4.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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胃癌是最常见的恶性肿瘤之一,由于目前的检查方法不能实现早期诊断,死亡率很高。具核梭杆菌(Fusobacteriumnucleatum,Fn)主要在口腔内定植,与胃肠道肿瘤的发生发展密切相关。唾液Fn与GC的关系目前尚不清楚。探讨唾液Fn是否可作为胃癌诊断的生物标志物,并探讨Fn对胃癌细胞的影响。采用液滴数字聚合酶链反应(droplet digital polymerase chain reaction,DPCR)技术,对2019年1月至2020年12月山东大学齐鲁医院收治的120例胃癌患者、31例萎缩性胃炎(atrophic gastritis,AG)患者、35例非AG(non-AG,NAG)患者、26例胃息肉(gastric polypt,GP)患者和20例正常对照(normal control,NC)患者唾液中Fn丰度进行定量。采用受试者工作特征(ROC)曲线分析Fn与传统血清肿瘤标志物癌胚抗原(CEA)、糖链抗原(CA)19-9、CA 72 -4的诊断价值。采用Transwell法和伤口愈合法检测Fn对胃癌细胞的影响。采用免疫印迹法检测上皮间质转化(EMT)标志物的表达。结果发现,胃癌患者唾液Fn水平显著高于AG、NAG、GP和NC(P < 0.001)。ROC曲线分析显示Fn诊断胃癌的敏感性为73.33%,特异性为82.14%,曲线下面积为0.813,优于CEA、CA 19 -9、CA 72 -4、铁蛋白和唾液酸,且具有上级诊断价值。胃癌患者唾液Fn水平随TNM分期增高而增高。胃癌有淋巴结转移者Fn水平高于无淋巴结转移者。transwell和伤口愈合实验均表明Fn感染促进了胃癌细胞的迁移和侵袭。Western blot分析显示,Fn感染后E-cadherin的表达降低,N-cadherin、vimentin和snail的表达增加。唾液中Fn的丰度可作为诊断胃癌的生物标志物,Fn感染可通过加速EMT过程促进胃癌转移。
As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis. Fusobacterium nucleatum (Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC. To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells. The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay. We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC (P < 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail. Fn abundance in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process.
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