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Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer
BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as bio...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919021/ https://www.ncbi.nlm.nih.gov/pubmed/35321281 http://dx.doi.org/10.4251/wjgo.v14.i3.690 |
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author | Ye, Li-Ping Mao, Xin-Li Zhou, Xian-Bin Wang, Yi Xu, Shi-Wen He, Sai-Qin Qian, Zi-Liang Zhang, Xiao-Gang Zhai, Li-Juan Peng, Jin-Bang Gu, Bin-Bin Jin, Xiu-Xiu Song, Ya-Qi Li, Shao-Wei |
author_facet | Ye, Li-Ping Mao, Xin-Li Zhou, Xian-Bin Wang, Yi Xu, Shi-Wen He, Sai-Qin Qian, Zi-Liang Zhang, Xiao-Gang Zhai, Li-Juan Peng, Jin-Bang Gu, Bin-Bin Jin, Xiu-Xiu Song, Ya-Qi Li, Shao-Wei |
author_sort | Ye, Li-Ping |
collection | PubMed |
description | BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori-enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes (P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine. |
format | Online Article Text |
id | pubmed-8919021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-89190212022-03-22 Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer Ye, Li-Ping Mao, Xin-Li Zhou, Xian-Bin Wang, Yi Xu, Shi-Wen He, Sai-Qin Qian, Zi-Liang Zhang, Xiao-Gang Zhai, Li-Juan Peng, Jin-Bang Gu, Bin-Bin Jin, Xiu-Xiu Song, Ya-Qi Li, Shao-Wei World J Gastrointest Oncol Basic Study BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori-enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes (P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine. Baishideng Publishing Group Inc 2022-03-15 2022-03-15 /pmc/articles/PMC8919021/ /pubmed/35321281 http://dx.doi.org/10.4251/wjgo.v14.i3.690 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Basic Study Ye, Li-Ping Mao, Xin-Li Zhou, Xian-Bin Wang, Yi Xu, Shi-Wen He, Sai-Qin Qian, Zi-Liang Zhang, Xiao-Gang Zhai, Li-Juan Peng, Jin-Bang Gu, Bin-Bin Jin, Xiu-Xiu Song, Ya-Qi Li, Shao-Wei Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title | Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title_full | Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title_fullStr | Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title_full_unstemmed | Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title_short | Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
title_sort | cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919021/ https://www.ncbi.nlm.nih.gov/pubmed/35321281 http://dx.doi.org/10.4251/wjgo.v14.i3.690 |
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