Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach

<b>Background/Objectives</b>: This study aimed to identify molecular variants associated with the progression of gastric precancerous lesions in a follow-up study conducted on patients from Southwestern Colombia. <b>Methods</b>: Whole-exome sequencing (WES) was performed on p...

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Main Authors: Lizeth Mejia-Ortiz, Jovanny Zabaleta, Jone Garai, Luis Eduardo Bravo, Andres Castillo
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Gastrointestinal Disorders
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Online Access:https://www.mdpi.com/2624-5647/7/2/30
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author Lizeth Mejia-Ortiz
Jovanny Zabaleta
Jone Garai
Luis Eduardo Bravo
Andres Castillo
author_facet Lizeth Mejia-Ortiz
Jovanny Zabaleta
Jone Garai
Luis Eduardo Bravo
Andres Castillo
author_sort Lizeth Mejia-Ortiz
collection DOAJ
description <b>Background/Objectives</b>: This study aimed to identify molecular variants associated with the progression of gastric precancerous lesions in a follow-up study conducted on patients from Southwestern Colombia. <b>Methods</b>: Whole-exome sequencing (WES) was performed on patients enrolled in the Colombian chemoprevention trial, who were classified into two groups—progression and regression—based on changes in the severity of their gastric precancerous lesions over 16 years of follow-up. The bioinformatics pipeline included steps for quality control, mapping, variant calling, filtering, and annotation. Associations between molecular variants and lesion progression were analyzed using Fisher’s exact test and the Cochran–Armitage trend test. Additionally, functional impact and pathway enrichment analyses were performed for variants that showed significant associations. <b>Results</b>: Thirty-eight molecular variants from thirty-seven participants were associated with the progression of gastric precancerous lesions. These variants were found in tumor suppressor genes like <i>CDKN2A</i> and <i>CDK4</i>, which are involved in cell cycle regulation and apoptosis. Additionally, variants were identified in extracellular matrix regulators such as <i>COL23A1</i>, <i>LAMA2</i>, and <i>TNR</i>. Other noteworthy findings included variants in <i>FLT1</i>, which is linked to VEGF signaling in angiogenesis, and <i>APOB</i>, which is involved in modulating inflammatory responses. Furthermore, alterations in genes associated with the hemostatic system, such as <i>FGA</i> and <i>F5</i>, underscored the connection between hemostasis and carcinogenesis. <b>Conclusions</b>: This exploratory analysis highlighted some molecular variants that may affect the function, structure, and expression of key proteins involved in cancer development, contributing to the progression of gastric precancerous lesions.
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spelling doaj-art-4e817e739b6e4b64959b97e667cfc0422025-08-20T03:27:15ZengMDPI AGGastrointestinal Disorders2624-56472025-04-01723010.3390/gidisord7020030Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory ApproachLizeth Mejia-Ortiz0Jovanny Zabaleta1Jone Garai2Luis Eduardo Bravo3Andres Castillo4TAO-Lab, Centre for Bioinformatics and Photonics-CIBioFi, Universidad del Valle, Cali 760032, ColombiaDepartment of Interdisciplinary Oncology, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USAStanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USARegistro Poblacional de Cancer de Cali, Department of Pathology, School of Medicine, Universidad del Valle, Cali 760032, ColombiaTAO-Lab, Centre for Bioinformatics and Photonics-CIBioFi, Universidad del Valle, Cali 760032, Colombia<b>Background/Objectives</b>: This study aimed to identify molecular variants associated with the progression of gastric precancerous lesions in a follow-up study conducted on patients from Southwestern Colombia. <b>Methods</b>: Whole-exome sequencing (WES) was performed on patients enrolled in the Colombian chemoprevention trial, who were classified into two groups—progression and regression—based on changes in the severity of their gastric precancerous lesions over 16 years of follow-up. The bioinformatics pipeline included steps for quality control, mapping, variant calling, filtering, and annotation. Associations between molecular variants and lesion progression were analyzed using Fisher’s exact test and the Cochran–Armitage trend test. Additionally, functional impact and pathway enrichment analyses were performed for variants that showed significant associations. <b>Results</b>: Thirty-eight molecular variants from thirty-seven participants were associated with the progression of gastric precancerous lesions. These variants were found in tumor suppressor genes like <i>CDKN2A</i> and <i>CDK4</i>, which are involved in cell cycle regulation and apoptosis. Additionally, variants were identified in extracellular matrix regulators such as <i>COL23A1</i>, <i>LAMA2</i>, and <i>TNR</i>. Other noteworthy findings included variants in <i>FLT1</i>, which is linked to VEGF signaling in angiogenesis, and <i>APOB</i>, which is involved in modulating inflammatory responses. Furthermore, alterations in genes associated with the hemostatic system, such as <i>FGA</i> and <i>F5</i>, underscored the connection between hemostasis and carcinogenesis. <b>Conclusions</b>: This exploratory analysis highlighted some molecular variants that may affect the function, structure, and expression of key proteins involved in cancer development, contributing to the progression of gastric precancerous lesions.https://www.mdpi.com/2624-5647/7/2/30gastric precancerous lesionsgenetic susceptibilitymolecular variantswhole exome sequencing
spellingShingle Lizeth Mejia-Ortiz
Jovanny Zabaleta
Jone Garai
Luis Eduardo Bravo
Andres Castillo
Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
Gastrointestinal Disorders
gastric precancerous lesions
genetic susceptibility
molecular variants
whole exome sequencing
title Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
title_full Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
title_fullStr Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
title_full_unstemmed Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
title_short Whole-Exome Sequencing Identified Molecular Variants Linked to the Progression of Gastric Precancerous Lesions in Patients from Southwestern Colombia—An Exploratory Approach
title_sort whole exome sequencing identified molecular variants linked to the progression of gastric precancerous lesions in patients from southwestern colombia an exploratory approach
topic gastric precancerous lesions
genetic susceptibility
molecular variants
whole exome sequencing
url https://www.mdpi.com/2624-5647/7/2/30
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