Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients
The ribosomal DNA (rDNA) can act as a sensor and responder of cancer-associated stress. Here we investigated rDNA copy number in gastric cancers and its association with existing biomarkers and metals exposure. This study was performed on paired tumor and adjacent normal tissues obtained from 65 gas...
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Elsevier
2020-05-01
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Series: | Environment International |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412019339091 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lingfang Feng Jing Du Chunji Yao Zhaoqiang Jiang Tao Li Quan Zhang Xinnian Guo Min Yu Hailing Xia Li Shi Junlin Jia Yan Tong Li Ju Jiaqi Liu Jianlin Lou Bernardo Lemos |
spellingShingle |
Lingfang Feng Jing Du Chunji Yao Zhaoqiang Jiang Tao Li Quan Zhang Xinnian Guo Min Yu Hailing Xia Li Shi Junlin Jia Yan Tong Li Ju Jiaqi Liu Jianlin Lou Bernardo Lemos Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients Environment International |
author_facet |
Lingfang Feng Jing Du Chunji Yao Zhaoqiang Jiang Tao Li Quan Zhang Xinnian Guo Min Yu Hailing Xia Li Shi Junlin Jia Yan Tong Li Ju Jiaqi Liu Jianlin Lou Bernardo Lemos |
author_sort |
Lingfang Feng |
title |
Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
title_short |
Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
title_full |
Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
title_fullStr |
Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
title_full_unstemmed |
Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
title_sort |
ribosomal dna copy number is associated with p53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patients |
publisher |
Elsevier |
series |
Environment International |
issn |
0160-4120 |
publishDate |
2020-05-01 |
description |
The ribosomal DNA (rDNA) can act as a sensor and responder of cancer-associated stress. Here we investigated rDNA copy number in gastric cancers and its association with existing biomarkers and metals exposure. This study was performed on paired tumor and adjacent normal tissues obtained from 65 gastric cancer patients who underwent gastrectomy. Immunohistochemistry was used to assess HER-2, E-cadherin, EGFR, CK (pan), CK20, CK7, TopoⅡ, CAM5.2, P53, and Ki-67 expression. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 17 metals in gastric tissues. rDNA copy number was detected by qPCR in genomic DNA isolated from tissue samples. Associations between the expression of existing markers, metal concentrations, and rDNA copy number were evaluated. Within patients with gastric cancer, the copy number of the 45S rDNA components (18S, 5.8S, 28S) and the 5S rDNA in tumor tissues were significantly higher than those in adjacent normal tissues, whereas mitochondrial DNA (mtDNA) copy number was significantly lower in tumor tissues than that in adjacent normal tissues. Further analysis revealed that the increase in 18S, 5.8S, and 28S rDNA copy number in tumor tissues was diminished in the context of EGFR and P53 loss. Moreover, analysis of metals revealed particularly high concentrations of As, Cd, Cr, Cu and Fe in the gastric tissues of these patients. Intriguingly, rDNA copy number variation across individuals was correlated with the concentrations of some metals. The rDNA was amplified in tumor tissues of gastric cancer patients, and its amplification may be associated with metals exposure. The expression of EGFR and P53 may influence rDNA copy number, with diminished amplification of the rDNA in cancers that were negative for these biomarkers. Our observation further our understanding of rDNA copy number in gastric cancer and its potential as a simple and useful marker in gastric cancer monitoring. Keywords: Gastric cancer, rDNA, Markers, Metals, Carcinogenesis |
url |
http://www.sciencedirect.com/science/article/pii/S0160412019339091 |
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doaj-c5a51bf7f193472ba5f8a49864a5d3bd2020-11-25T03:03:55ZengElsevierEnvironment International0160-41202020-05-01138Ribosomal DNA copy number is associated with P53 status and levels of heavy metals in gastrectomy specimens from gastric cancer patientsLingfang Feng0Jing Du1Chunji Yao2Zhaoqiang Jiang3Tao Li4Quan Zhang5Xinnian Guo6Min Yu7Hailing Xia8Li Shi9Junlin Jia10Yan Tong11Li Ju12Jiaqi Liu13Jianlin Lou14Bernardo Lemos15Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaDepartment of Gastroenterology, Zhejiang Provincial People’s Hospital, Hangzhou, China; People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaInstitute of Hygiene, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaCenter for Biostatistics, Bioinformatics and Big Data, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaAffiliated Hangzhou First People's Hospital Zhejiang University School of Medicine, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, ChinaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, Hangzhou, China; Hangzhou Medical College, Hangzhou, China; Corresponding author at: Institute of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou 310013, Zhejiang, China.Department of Environmental Health, Harvard University T.H. Chan School of Public Health, Boston, USAThe ribosomal DNA (rDNA) can act as a sensor and responder of cancer-associated stress. Here we investigated rDNA copy number in gastric cancers and its association with existing biomarkers and metals exposure. This study was performed on paired tumor and adjacent normal tissues obtained from 65 gastric cancer patients who underwent gastrectomy. Immunohistochemistry was used to assess HER-2, E-cadherin, EGFR, CK (pan), CK20, CK7, TopoⅡ, CAM5.2, P53, and Ki-67 expression. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 17 metals in gastric tissues. rDNA copy number was detected by qPCR in genomic DNA isolated from tissue samples. Associations between the expression of existing markers, metal concentrations, and rDNA copy number were evaluated. Within patients with gastric cancer, the copy number of the 45S rDNA components (18S, 5.8S, 28S) and the 5S rDNA in tumor tissues were significantly higher than those in adjacent normal tissues, whereas mitochondrial DNA (mtDNA) copy number was significantly lower in tumor tissues than that in adjacent normal tissues. Further analysis revealed that the increase in 18S, 5.8S, and 28S rDNA copy number in tumor tissues was diminished in the context of EGFR and P53 loss. Moreover, analysis of metals revealed particularly high concentrations of As, Cd, Cr, Cu and Fe in the gastric tissues of these patients. Intriguingly, rDNA copy number variation across individuals was correlated with the concentrations of some metals. The rDNA was amplified in tumor tissues of gastric cancer patients, and its amplification may be associated with metals exposure. The expression of EGFR and P53 may influence rDNA copy number, with diminished amplification of the rDNA in cancers that were negative for these biomarkers. Our observation further our understanding of rDNA copy number in gastric cancer and its potential as a simple and useful marker in gastric cancer monitoring. Keywords: Gastric cancer, rDNA, Markers, Metals, Carcinogenesishttp://www.sciencedirect.com/science/article/pii/S0160412019339091 |