A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer
BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Canc...
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| Format: | Article |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.584213/full |
| _version_ | 1818584682820796416 |
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| author | Bingdong Zhang Yuerui Li Liu Yang Yongbing Chen |
| author_facet | Bingdong Zhang Yuerui Li Liu Yang Yongbing Chen |
| author_sort | Bingdong Zhang |
| collection | DOAJ |
| description | BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma. |
| first_indexed | 2024-12-16T08:25:04Z |
| format | Article |
| id | doaj.art-93883daaa180476b8e87b27bdaf66863 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T08:25:04Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-93883daaa180476b8e87b27bdaf668632022-12-21T22:38:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.584213584213A Four−Gene-Based Risk Score With High Prognostic Value in Gastric CancerBingdong Zhang0Yuerui Li1Liu Yang2Yongbing Chen3Department of Gastrointestinal Surgery & Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaGeriatric Cardiology Department of The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army of China General Hospital, Beijing, ChinaState Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing, ChinaDepartment of Gastrointestinal Surgery & Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaBackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.https://www.frontiersin.org/articles/10.3389/fonc.2021.584213/fullgastric cancerrisk scoremutationsprognostic valuegenome |
| spellingShingle | Bingdong Zhang Yuerui Li Liu Yang Yongbing Chen A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer Frontiers in Oncology gastric cancer risk score mutations prognostic value genome |
| title | A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer |
| title_full | A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer |
| title_fullStr | A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer |
| title_full_unstemmed | A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer |
| title_short | A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer |
| title_sort | four gene based risk score with high prognostic value in gastric cancer |
| topic | gastric cancer risk score mutations prognostic value genome |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.584213/full |
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