Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database
Abstract Background Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non‐synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. Aim The aim of this study is...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1906 |
| _version_ | 1797344687338553344 |
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| author | Mohammad Uzzal Hossain Ishtiaque Ahammad Md. Moniruzzaman Mahbuba Akter Lubna Arittra Bhattacharjee Zeshan Mahmud Chowdhury Istiak Ahmed Md. Billal Hosen Shourov Biswas Keshob Chandra Das Chaman Ara Keya Md. Salimullah |
| author_facet | Mohammad Uzzal Hossain Ishtiaque Ahammad Md. Moniruzzaman Mahbuba Akter Lubna Arittra Bhattacharjee Zeshan Mahmud Chowdhury Istiak Ahmed Md. Billal Hosen Shourov Biswas Keshob Chandra Das Chaman Ara Keya Md. Salimullah |
| author_sort | Mohammad Uzzal Hossain |
| collection | DOAJ |
| description | Abstract Background Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non‐synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. Aim The aim of this study is to examine the nsSNP in GC‐associated genes. The study also aims to develop a database with extensive information regarding the nsSNPs in the GC‐associated genes and their impacts. Methods and Results A total of 34,588 nsSNPs from 1,493,460 SNPs of the 40 genes were extracted from the available SNP database. Drug binding and energy minimization were examined by molecular docking and YASARA. To validate the existence of the germline CDH1 gene mutation (rs34466743) in the isolated blood DNA of gastric cancer (GC) patients, polymerase chain reaction (PCR) and DNA sequencing were performed. According to the results of the gene network analysis, 17 genes may interact with other types of cancer. A total of 11,363 nsSNPs were detected within the 40 GC genes. Among these, 474 nsSNPs were predicted to be damaging and 40 to be the most damaging. The SNPs in domain regions were thought to be strong candidates that alter protein functions. Our findings proposed that most of the selected nsSNPs were within the domains or motif regions. Free Energy Deviation calculation of protein structure pointed toward noteworthy changes in the structure of each protein that can demolish its natural function. Subsequently, drug binding confirmed the structural variation and the ineffectiveness of the drug against the mutant model in individuals with these germline variants. Furthermore, in vitro analysis of the rs34466743 germline variant from the CDH1 gene confirmed the strength and robustness of the pipeline that could expand the somatic alteration for causing cancer. In addition, a comprehensive gastric cancer polymorphism database named “GasCanBase” was developed to make data available to researchers. Conclusion The findings of this study and the “GasCanBase” database may greatly contribute to our understanding of molecular epidemiology and the development of precise therapeutics for gastric cancer. GasCanBase is available at: https://www.gascanbase.com/. |
| first_indexed | 2024-03-08T11:06:21Z |
| format | Article |
| id | doaj.art-71b510e2b7c540b1af7e0c69582aee48 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-08T11:06:21Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-71b510e2b7c540b1af7e0c69582aee482024-01-26T14:41:21ZengWileyCancer Reports2573-83482023-12-01612n/an/a10.1002/cnr2.1906Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” databaseMohammad Uzzal Hossain0Ishtiaque Ahammad1Md. Moniruzzaman2Mahbuba Akter Lubna3Arittra Bhattacharjee4Zeshan Mahmud Chowdhury5Istiak Ahmed6Md. Billal Hosen7Shourov Biswas8Keshob Chandra Das9Chaman Ara Keya10Md. Salimullah11Bioinformatics Division National Institute of Biotechnology Dhaka BangladeshBioinformatics Division National Institute of Biotechnology Dhaka BangladeshMolecular Biotechnology Division National Institute of Biotechnology Dhaka BangladeshBioinformatics Division National Institute of Biotechnology Dhaka BangladeshBioinformatics Division National Institute of Biotechnology Dhaka BangladeshBioinformatics Division National Institute of Biotechnology Dhaka BangladeshDepartment of Pharmacy Noakhali Science and Technology University Noakhali BangladeshDepartment of Pharmacy Noakhali Science and Technology University Noakhali BangladeshDepartment of Clinical Oncology Bangabandhu Sheikh Mujib Medical University Dhaka BangladeshMolecular Biotechnology Division National Institute of Biotechnology Dhaka BangladeshDepartment of Biochemistry and Microbiology North South University Dhaka BangladeshMolecular Biotechnology Division National Institute of Biotechnology Dhaka BangladeshAbstract Background Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non‐synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. Aim The aim of this study is to examine the nsSNP in GC‐associated genes. The study also aims to develop a database with extensive information regarding the nsSNPs in the GC‐associated genes and their impacts. Methods and Results A total of 34,588 nsSNPs from 1,493,460 SNPs of the 40 genes were extracted from the available SNP database. Drug binding and energy minimization were examined by molecular docking and YASARA. To validate the existence of the germline CDH1 gene mutation (rs34466743) in the isolated blood DNA of gastric cancer (GC) patients, polymerase chain reaction (PCR) and DNA sequencing were performed. According to the results of the gene network analysis, 17 genes may interact with other types of cancer. A total of 11,363 nsSNPs were detected within the 40 GC genes. Among these, 474 nsSNPs were predicted to be damaging and 40 to be the most damaging. The SNPs in domain regions were thought to be strong candidates that alter protein functions. Our findings proposed that most of the selected nsSNPs were within the domains or motif regions. Free Energy Deviation calculation of protein structure pointed toward noteworthy changes in the structure of each protein that can demolish its natural function. Subsequently, drug binding confirmed the structural variation and the ineffectiveness of the drug against the mutant model in individuals with these germline variants. Furthermore, in vitro analysis of the rs34466743 germline variant from the CDH1 gene confirmed the strength and robustness of the pipeline that could expand the somatic alteration for causing cancer. In addition, a comprehensive gastric cancer polymorphism database named “GasCanBase” was developed to make data available to researchers. Conclusion The findings of this study and the “GasCanBase” database may greatly contribute to our understanding of molecular epidemiology and the development of precise therapeutics for gastric cancer. GasCanBase is available at: https://www.gascanbase.com/.https://doi.org/10.1002/cnr2.1906bioinformaticsdatabaseGasCanBasegastric cancerpolymorphismSNP |
| spellingShingle | Mohammad Uzzal Hossain Ishtiaque Ahammad Md. Moniruzzaman Mahbuba Akter Lubna Arittra Bhattacharjee Zeshan Mahmud Chowdhury Istiak Ahmed Md. Billal Hosen Shourov Biswas Keshob Chandra Das Chaman Ara Keya Md. Salimullah Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database Cancer Reports bioinformatics database GasCanBase gastric cancer polymorphism SNP |
| title | Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database |
| title_full | Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database |
| title_fullStr | Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database |
| title_full_unstemmed | Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database |
| title_short | Investigation of pathogenic germline variants in gastric cancer and development of “GasCanBase” database |
| title_sort | investigation of pathogenic germline variants in gastric cancer and development of gascanbase database |
| topic | bioinformatics database GasCanBase gastric cancer polymorphism SNP |
| url | https://doi.org/10.1002/cnr2.1906 |
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