Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20230409.001
- VernacularTitle:具核梭杆菌诱导内质网应激相关蛋白GRP78及XBP1高表达在食管鳞癌中的临床意义
- Author:
Si-mo CHEN
1
;
Zhe-yuan ZHANG
2
;
Jia-hao ZHANG
1
;
Ke-yao HE
1
;
Yi-wen LIU
2
;
Fu-you ZHOU
1
Author Information
1. Department of Thoracic Surgery， The Third Affiliated Hospital of Xinxiang Medical University， Xinxiang 453003，China
2. College of Clinical Medicine of Henan University of Science and Technology // The First Affiliated Hospital of Henan University of Science and Technology // Henan Key Laboratory of Cancer Epigenetics // Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment， Luoyang 471003，China
- Publication Type:Journal Article
- Keywords:
esophageal squamous cell carcinoma;
fusobacterium nucleatum;
endoplasmic reticulum stress;
GRP78;
XBP1;
prognosis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2023;44(3):403-415
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.
