Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by <italic style="font-style: italic">Fusobacterium Nucleatum</italic> in Esophageal Squamous Cell Carcinoma

CHEN Si-mo; ZHANG Zhe-yuan; ZHANG Jia-hao; HE Ke-yao; LIU Yi-wen; ZHOU Fu-you

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20230409.001

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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

Basic Research | 更新时间：2024-02-19

- 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
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 44, Issue 3, Pages: 403-415(2023)
- 作者机构：
  
  1.新乡医学院第三附属医院胸外科，河南新乡，453003
  2.河南科技大学临床医学院//河南科技大学第一附属医院//河南省肿瘤表观遗传重点实验室//河南省微生态与食管癌防治重点实验室，河南洛阳，471003
  3.安阳市肿瘤医院胸外科//河南省食管癌精准防治医学重点实验室，河南安阳 455000
- 作者简介：
  
  ZHOU Fu-you； E-mail： ayzhoufuyou@163.com
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20230409.001
  CLC： R735
- Received：08 November 2022，
  
  Published：20 May 2023
- 稿件说明：
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陈斯默,张哲源,张家豪等.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[J].中山大学学报（医学科学版）,2023,44(03):403-415.

CHEN Si-mo,ZHANG Zhe-yuan,ZHANG Jia-hao,et al.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[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):403-415.
陈斯默,张哲源,张家豪等.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[J].中山大学学报（医学科学版）,2023,44(03):403-415. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20230409.001.

CHEN Si-mo,ZHANG Zhe-yuan,ZHANG Jia-hao,et al.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[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):403-415. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20230409.001.

摘要

目的

分析食管鳞癌（ESCC）中具核梭杆菌（Fn）对内质网应激相关蛋白葡萄糖调节蛋白78（GRP78）及X盒结合蛋白1（XBP1）的诱导效应，并探讨其潜在机制及临床意义。

方法

采用Fn感染ESCC细胞KYSE150及KYSE140不同时间（12 h、24 h及48 h），通过氧化应激指标试剂盒及Western blot检测各组细胞中氧化应激指标（ROS、MDA与SOD）及GRP78与XBP1的表达情况。实验分为Fn组，Fn+siNC1组，Fn+siGRP78组，Fn+siNC2组及Fn+siXBP1组，比较各组细胞中氧化应激指标、紫杉醇（PTX）应答效力、增殖、侵袭及转移能力差异。采用RNA scope及免疫组化法检测234例ESCC组织及癌旁组织中Fn感染及GRP78与XBP1的表达情况。利用卡方检验分析各因素与患者临床病理特征之间的相关性。采用Kaplan-Meier生存分析比较各因素对患者生存期的影响。

结果

与Fn未感染的KYSE150及KYSE140组细胞相比，Fn感染组（12 h、24 h及48 h）细胞中ROS与MDA含量逐渐增加，SOD活性逐渐降低，且GRP78及XBP1表达量逐渐增高（均

0.05）。与Fn组、Fn+siNC1组及Fn+siNC2组相比，Fn+siGRP78组及Fn+siXBP1组细胞中ROS与MDA含量减少，SOD活性增强，PTX应答效力增强，增殖、侵袭及转移能力减弱（均

0.05）。ESCC组织中Fn感染率、GRP78及XBP1阳性率分别为43.16%、69.66%及60.68%，三者具有显著一致性（

0.05）。Fn感染阳性、GRP78及XBP1高表达的患者多为有吸烟、饮酒史的男性患者，且肿瘤分化程度低、浸润程度深、淋巴结转移率高、临床分期多为Ⅲ/Ⅳ期。三者阳性组的患者5年生存期均缩短（

0.05）。

结论

Fn可通过诱导GRP78及XBP1高表达，引发内质网应激，促进ESCC恶性演进。

Abstract

Objective

To 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.

Methods

ESCC 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.

Results

Compared 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）（

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 （

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 （

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 （

0.05）.

Conclusions

could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

关键词

Keywords

references

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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

Department of Thoracic Surgery， Anyang Tumor Hospital； Henan Key Laboratory of Precision Medicine for Prevention and Treatment of Esophageal Cancer

Guangdong Engineering Research Center for Gene Manipulation and Bio-macromolecular Products

Zhongshan School of Medicine， Sun Yat-sen University

Department of Biochemistry and Molecular Biology， Zhongshan School of Medicine， Sun Yat-sen University

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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

DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20230409.001

摘要

Abstract

关键词

Keywords

references