摘要
目的:探究鼻咽癌放化疗后口腔感染患者组织Toll样受体2(TLR2)/Toll样受体4(TLR4)与Janus激酶2(JAK2)/信号传导和转录激活子3(STAT3)通路表达水平变化。方法:以2023年1月~2024年9月间广西中医药大学第一附属医院收治的53例鼻咽癌放化疗后发生口腔感染的患者作为感染组,同期选取53例鼻咽癌放化疗后未发生口腔感染的患者作为未感染组。分析鼻咽癌放化疗后发生口腔感染患者病原菌分布、临床资料、口腔黏膜组织TLR2/TLR4与JAK2/STAT3通路表达水平,并分析鼻咽癌放化疗后口腔感染的危险因素及口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路对鼻咽癌放化疗后口腔感染的诊断价值。结果:53例鼻咽癌放化疗后口腔感染患者共分离出61株病原菌,真菌、革兰阴性菌和革兰阳性菌分别检出36、19和6株。感染组糖尿病、吸烟史、口腔疾病史、放化疗周期多次、口腔环境不良的患者占比高于未感染组(P<0.05),血清白蛋白水平则低于未感染组(P<0.05)。感染组口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路信使核糖核酸(mRNA)表达水平高于未感染组(P<0.05);Western Blot法检测口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路蛋白表达水平,感染组高于未感染组(P<0.05);免疫组化法检测口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路蛋白阳性表达率,感染组高于未感染组(P<0.05)。多因素Logistic回归分析结果显示,放化疗周期多次、口腔环境不良、血清白蛋白水平偏低、口腔黏膜组织TLR2 mRNA偏高、口腔黏膜组织TLR4 mRNA偏高、口腔黏膜组织JAK2 mRNA偏高、口腔黏膜组织STAT3 mRNA偏高均为鼻咽癌放化疗后口腔感染的危险因素(OR=2.030、1.385、1.811、1.357、1.808、1.231、2.784,P<0.05)。将感染组患者作为阳性病例,将未感染组患者作为阴性对照,受试者工作特征曲线分析结果显示,口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路mRNA表达联合诊断鼻咽癌放化疗后口腔感染的曲线下面积值高于4者单独检测(P<0.05)。结论:鼻咽癌放化疗后口腔感染患者病原菌主要为真菌,其危险因素包括放化疗周期多次、口腔环境不良、血清白蛋白水平偏低、口腔黏膜组织TLR2 mRNA偏高、口腔黏膜组织TLR4 mRNA偏高、口腔黏膜组织JAK2 mRNA偏高、口腔黏膜组织STAT3 mRNA偏高,且口腔黏膜组织TLR2/TLR4、JAK2/STAT3通路mRNA表达联合诊断鼻咽癌放化疗后口腔感染的价值高于各项单独检测。
Objective To explore the expression changes of Toll-like receptor 2(TLR2)/Toll-like receptor 4(TLR4)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathways in the nasopharyngeal carcinoma(NPC)patients with oral infection after chemoradiotherapy.Methods Fifty-three NPC patients with post-chemoradiotherapy oral infection admitted to the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2023 to September 2024 were enrolled as the infection group,while another 53 NPC patients without post-chemoradiotherapy oral infection during the same period were selected as the non-infection group.For NPC patients with post-chemoradiotherapy oral infection,the distribution of pathogenic bacteria,clinical data,TLR2/TLR4 and JAK2/STAT3 pathway expressions in oral mucosal tissues were analyzed.Additionally,the risk factors for post-chemoradiotherapy oral infection were identified,and the diagnostic value of TLR2/TLR4 and JAK2/STAT3 pathway expressions in oral mucosal tissues was evaluated.Results A total of 61 strains of pathogenic bacteria were isolated from 53 NPC patients with post-chemoradiotherapy oral infection,including 36 strains of fungi,19 strains of Gram-negative bacteria,and 6 strains of Gram-positive bacteria.Compared with the non-infection group,the infection group had significantly higher proportions of patients with diabetes,smoking history,oral disease history,multiple chemoradiotherapy cycles,and poor oral hygiene,while lower serum albumin level(all P<0.05).The infection group had up-regulated TLR2/TLR4 and JAK2/STAT3 pathway mRNA expressions in oral mucosal tissues than the non-infection group(P<0.05).Western Blot assay showed that the TLR2/TLR4 and JAK2/STAT3 pathway protein expression levels in oral mucosal tissues significantly elevated in the infection group than the non-infection group(P<0.05).Immunohistochemistry assay revealed higher positive expression rates of TLR2/TLR4 and JAK2/STAT3 pathway proteins in oral mucosal tissues in the infection group as compared with the non-infection group(P<0.05).Multivariate Logistic regression analysis identified multiple chemoradiotherapy cycles,poor oral hygiene,low serum albumin level,and increased TLR2,TLR4,JAK2,and STAT3 mRNA expressions in oral mucosal tissues as risk factors for oral infection after chemoradiotherapy for NPC(OR=2.030,1.385,1.811,1.357,1.808,1.231,2.784,respectively;P<0.05).Taking the infection group as positive cases and the non-infection group as negative controls,receiver operating characteristic curve analysis showed that the area under the curve of the combined detection of TLR2/TLR4 and JAK2/STAT3 pathway mRNA expressions in oral mucosal tissues for diagnosing oral infection after chemoradiotherapy for NPC was significantly higher than that of each single indicator(P<0.05).Conclusion Fungi are the dominant pathogenic bacteria in NPC patients with post-chemoradiotherapy oral infection.Multiple chemoradiotherapy cycles,poor oral hygiene,low serum albumin level,and increased TLR2,TLR4,JAK2 and STAT3 mRNA expressions in oral mucosal tissue are indentified as risk factors for oral infection after chemoradiotherapy for NPC.The combined detection of TLR2/TLR4 and JAK2/STAT3 pathway mRNA expressions in oral mucosal tissues exhibits higher diagnostic value than individual detection for post-chemoradiotherapy oral infection in NPC patients.
作者
龙皆存
蔡凯
王家盛
何宗林
胡乃强
岳桂华
LONG Jiecun;CAI Kai;WANG Jiasheng;HE Zonglin;HU Naiqiang;YUE Guihua(Graduate School,Guangxi University of Chinese Medicine,Nanning 530200,China;Department of Oncology,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530219,China)
出处
《中国医学物理学杂志》
2025年第12期1639-1646,共8页
Chinese Journal of Medical Physics
基金
国家自然科学基金(81860831,82360913)
广西自然科学基金(2020GXNSFAA297141)。
