Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients
Gastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consisten...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1206609/full |
| _version_ | 1797687639203119104 |
|---|---|
| author | Mariana Belén Velásquez Sotomayor Mariana Belén Velásquez Sotomayor Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Ricardo José Asurza Montalva Ricardo José Asurza Montalva Obert Marín-Sánchez Obert Marín-Sánchez Alexis Germán Murillo Carrasco Alexis Germán Murillo Carrasco César Alexander Ortiz Rojas César Alexander Ortiz Rojas |
| author_facet | Mariana Belén Velásquez Sotomayor Mariana Belén Velásquez Sotomayor Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Ricardo José Asurza Montalva Ricardo José Asurza Montalva Obert Marín-Sánchez Obert Marín-Sánchez Alexis Germán Murillo Carrasco Alexis Germán Murillo Carrasco César Alexander Ortiz Rojas César Alexander Ortiz Rojas |
| author_sort | Mariana Belén Velásquez Sotomayor |
| collection | DOAJ |
| description | Gastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consistently associated with prognosis in GC. Based on the ROC curve, patients were categorized into high and low-expression groups for each gene using the best cutoff point. Genes associated with survival (AUC > 0.5; univariate and multivariate Cox regressions, p < 0.05) were used to model gene expression-based scores by weighted sum using the pooled Cox β regression coefficients. Cox regression (p < 0.05), AUC > 0.5, sensitivity > 0.5, and specificity > 0.5 were considered to identify the best scores. Gene set enrichment analysis (KEGG, REACTOME, and Gene Ontology databases), as well as microenvironment composition and stromal cell signatures prediction (CIBERSORT, EPIC, xCell, MCP-counter, and quanTIseq web tools) were performed. We found 11 genes related to GC survival in the five independent cohorts. Then, we modeled scores by calculating all possible combinations between these genes. Among the 2,047 scores, we identified a panel based on the expression of seven genes. It was named GES7 and is composed of CCDC91, DYNC1I1, FAM83D, LBH, SLITRK5, WTIP, and NAP1L3 genes. GES7 features were validated in two independent external cohorts. Next, GES7 was found to recategorize patients from AJCC TNM stages into a best-fitted prognostic group. The GES7 was associated with activation of the TGF-β pathway and repression of anticancer immune cells. Finally, we compared the GES7 with 30 previous proposed scores, finding that GES7 is one of the most robust scores. As a result, the GES7 is a reliable gene-expression-based signature to improve the prognosis estimation in GC. |
| first_indexed | 2024-03-12T01:21:39Z |
| format | Article |
| id | doaj.art-8f39c5e9dcbe4080b830326739f2ea43 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T01:21:39Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8f39c5e9dcbe4080b830326739f2ea432023-09-13T05:17:58ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12066091206609Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patientsMariana Belén Velásquez Sotomayor0Mariana Belén Velásquez Sotomayor1Anthony Vladimir Campos Segura2Anthony Vladimir Campos Segura3Anthony Vladimir Campos Segura4Ricardo José Asurza Montalva5Ricardo José Asurza Montalva6Obert Marín-Sánchez7Obert Marín-Sánchez8Alexis Germán Murillo Carrasco9Alexis Germán Murillo Carrasco10César Alexander Ortiz Rojas11César Alexander Ortiz Rojas12Immunology and Cancer Research Group (IMMUCA), Lima, PeruEscuela de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, PerúImmunology and Cancer Research Group (IMMUCA), Lima, PeruBiochemistry and Molecular Biology Research Laboratory, Faculty of Natural Sciences and Mathematics, Universidad Nacional Federico Villarreal, Lima, PeruLaboratory of Genomics and Molecular Biology, International Center of Research CIPE, A.C. Camargo Cancer Center, Sao Paulo, BrazilImmunology and Cancer Research Group (IMMUCA), Lima, PeruEscuela de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, PerúImmunology and Cancer Research Group (IMMUCA), Lima, PeruDepartamento Académico de Microbiología Médica, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, PeruImmunology and Cancer Research Group (IMMUCA), Lima, PeruCentro de Investigação Translacional em Oncologia (LIM24), Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, São Paulo, BrazilImmunology and Cancer Research Group (IMMUCA), Lima, PeruLaboratório de Investigação Médica (LIM) 31, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilGastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consistently associated with prognosis in GC. Based on the ROC curve, patients were categorized into high and low-expression groups for each gene using the best cutoff point. Genes associated with survival (AUC > 0.5; univariate and multivariate Cox regressions, p < 0.05) were used to model gene expression-based scores by weighted sum using the pooled Cox β regression coefficients. Cox regression (p < 0.05), AUC > 0.5, sensitivity > 0.5, and specificity > 0.5 were considered to identify the best scores. Gene set enrichment analysis (KEGG, REACTOME, and Gene Ontology databases), as well as microenvironment composition and stromal cell signatures prediction (CIBERSORT, EPIC, xCell, MCP-counter, and quanTIseq web tools) were performed. We found 11 genes related to GC survival in the five independent cohorts. Then, we modeled scores by calculating all possible combinations between these genes. Among the 2,047 scores, we identified a panel based on the expression of seven genes. It was named GES7 and is composed of CCDC91, DYNC1I1, FAM83D, LBH, SLITRK5, WTIP, and NAP1L3 genes. GES7 features were validated in two independent external cohorts. Next, GES7 was found to recategorize patients from AJCC TNM stages into a best-fitted prognostic group. The GES7 was associated with activation of the TGF-β pathway and repression of anticancer immune cells. Finally, we compared the GES7 with 30 previous proposed scores, finding that GES7 is one of the most robust scores. As a result, the GES7 is a reliable gene-expression-based signature to improve the prognosis estimation in GC.https://www.frontiersin.org/articles/10.3389/fgene.2023.1206609/fullprognosisgastric cancerscorerisk classificationgene expression |
| spellingShingle | Mariana Belén Velásquez Sotomayor Mariana Belén Velásquez Sotomayor Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Anthony Vladimir Campos Segura Ricardo José Asurza Montalva Ricardo José Asurza Montalva Obert Marín-Sánchez Obert Marín-Sánchez Alexis Germán Murillo Carrasco Alexis Germán Murillo Carrasco César Alexander Ortiz Rojas César Alexander Ortiz Rojas Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients Frontiers in Genetics prognosis gastric cancer score risk classification gene expression |
| title | Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients |
| title_full | Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients |
| title_fullStr | Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients |
| title_full_unstemmed | Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients |
| title_short | Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients |
| title_sort | establishment of a 7 gene expression panel to improve the prognosis classification of gastric cancer patients |
| topic | prognosis gastric cancer score risk classification gene expression |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1206609/full |
| work_keys_str_mv | AT marianabelenvelasquezsotomayor establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT marianabelenvelasquezsotomayor establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT anthonyvladimircampossegura establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT anthonyvladimircampossegura establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT anthonyvladimircampossegura establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT ricardojoseasurzamontalva establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT ricardojoseasurzamontalva establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT obertmarinsanchez establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT obertmarinsanchez establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT alexisgermanmurillocarrasco establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT alexisgermanmurillocarrasco establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT cesaralexanderortizrojas establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients AT cesaralexanderortizrojas establishmentofa7geneexpressionpaneltoimprovetheprognosisclassificationofgastriccancerpatients |