Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer
Introduction: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients a...
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| Language: | English |
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Tabriz University of Medical Sciences
2024-11-01
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| Series: | BioImpacts |
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| Online Access: | https://bi.tbzmed.ac.ir/PDF/bi-14-30118.pdf |
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| author | Ya-Lin Han Li Chen Xu-Ning Wang Mao-Lin Xu Rui Qin Fang-Ming Gong Peng Sun Hong-Yi Liu Zhi-Peng Teng Zhao-Xia Li Guang-Hai Dai |
| author_facet | Ya-Lin Han Li Chen Xu-Ning Wang Mao-Lin Xu Rui Qin Fang-Ming Gong Peng Sun Hong-Yi Liu Zhi-Peng Teng Zhao-Xia Li Guang-Hai Dai |
| author_sort | Ya-Lin Han |
| collection | DOAJ |
| description | Introduction: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance. |
| format | Article |
| id | doaj-art-699d6727cf434ad7b932c2465b1b65c4 |
| institution | Kabale University |
| issn | 2228-5652 2228-5660 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | BioImpacts |
| spelling | doaj-art-699d6727cf434ad7b932c2465b1b65c42025-01-18T10:05:04ZengTabriz University of Medical SciencesBioImpacts2228-56522228-56602024-11-01146301183011810.34172/bi.2024.30118bi-30118Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancerYa-Lin Han0Li Chen1Xu-Ning Wang2Mao-Lin Xu3Rui Qin4Fang-Ming Gong5Peng Sun6Hong-Yi Liu7Zhi-Peng Teng8Zhao-Xia Li9Guang-Hai Dai10Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, ChinaDepartment of General Surgery, The Air Force Hospital of Northern Theater PLA, Shenyang 110042, ChinaDepartment of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Gastroenterology, The 305 Hospital of PLA, Beijing 100017, ChinaDepartment of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, ChinaDepartment of Oncology, PLA Rocket Force Characteristic Medical Centre, Beijing 100088, ChinaDepartment of Oncology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, ChinaIntroduction: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.https://bi.tbzmed.ac.ir/PDF/bi-14-30118.pdfmutated genesmolecular characteristicprognosisstage iii gastric cancertumour mutation burden |
| spellingShingle | Ya-Lin Han Li Chen Xu-Ning Wang Mao-Lin Xu Rui Qin Fang-Ming Gong Peng Sun Hong-Yi Liu Zhi-Peng Teng Zhao-Xia Li Guang-Hai Dai Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer BioImpacts mutated genes molecular characteristic prognosis stage iii gastric cancer tumour mutation burden |
| title | Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer |
| title_full | Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer |
| title_fullStr | Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer |
| title_full_unstemmed | Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer |
| title_short | Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer |
| title_sort | association of tumour mutation burden with prognosis and its clinical significance in stage iii gastric cancer |
| topic | mutated genes molecular characteristic prognosis stage iii gastric cancer tumour mutation burden |
| url | https://bi.tbzmed.ac.ir/PDF/bi-14-30118.pdf |
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