The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma
Abstract The mismatch repair (MMR) system plays a crucial role in the maintenance of DNA replication fidelity and genomic stability. The clinical value of the MMR molecular marker as an immunotherapy for advanced solid tumors has been documented. However, this therapy is not effective in some patien...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-84613-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559648700727296 |
|---|---|
| author | Zhihui Tian Lili Yang Rong Yang Wenhui Yang |
| author_facet | Zhihui Tian Lili Yang Rong Yang Wenhui Yang |
| author_sort | Zhihui Tian |
| collection | DOAJ |
| description | Abstract The mismatch repair (MMR) system plays a crucial role in the maintenance of DNA replication fidelity and genomic stability. The clinical value of the MMR molecular marker as an immunotherapy for advanced solid tumors has been documented. However, this therapy is not effective in some patients. This study aimed to develop an MMR-related molecular prognostic model for identifying appropriate populations of stomach adenocarcinoma (STAD) for better treatment outcome. The MMR genes expression data were downloaded from TCGA and CCLE databases. The expression of four MMR genes, construction of a prognostic risk model, and assessment of immune infiltration in STAD were performed using Xiantao online tool. GEPIA2 was used to explore the association of MMR genes expression with clinical stage and overall survival. The frequency and prognostic value of MMR genes in STAD were conducted on the cBioPortal. The MLH1 co-expression network was established based on the LinkedOmics database. This study found that the expression of MSH2, MSH6 and PMS2 was up-regulated in STAD tissues. Moreover, differential MMR genetic expression levels were not significantly correlated with the clinical stages of STAD. Besides, no significant difference in PFS or OS was observed in STAD patients with or without MMR genetic alteration. Moreover, MLH1 and MSH2 were used to establish a prognostic risk model. The immune infiltration levels of most immune cells were upregulated in the high-risk group with elevated expression of PDCD1 and low TMB score. Finally, we found that MLH1 was an independent predictor of STAD prognosis among the four MMR genes. An MMR-related prognostic model for STAD was constructed based on genes. This model provides a new therapeutic concept for the diagnosis and treatment of STAD. |
| format | Article |
| id | doaj-art-2fec017a827e4a4181065dc548e0edaf |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2fec017a827e4a4181065dc548e0edaf2025-01-05T12:19:52ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-84613-8The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinomaZhihui Tian0Lili Yang1Rong Yang2Wenhui Yang3Department of Gastroenterology, Shanxi Hospital Affiliated to Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Intensive Care Unit, Shanxi Hospital Affiliated to Cancer Hospital, Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Shanxi Medical UniversityDepartment of Gastroenterology, Shanxi Hospital Affiliated to Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityDepartment of Gastroenterology, Shanxi Hospital Affiliated to Cancer Hospital, Shanxi Province Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityAbstract The mismatch repair (MMR) system plays a crucial role in the maintenance of DNA replication fidelity and genomic stability. The clinical value of the MMR molecular marker as an immunotherapy for advanced solid tumors has been documented. However, this therapy is not effective in some patients. This study aimed to develop an MMR-related molecular prognostic model for identifying appropriate populations of stomach adenocarcinoma (STAD) for better treatment outcome. The MMR genes expression data were downloaded from TCGA and CCLE databases. The expression of four MMR genes, construction of a prognostic risk model, and assessment of immune infiltration in STAD were performed using Xiantao online tool. GEPIA2 was used to explore the association of MMR genes expression with clinical stage and overall survival. The frequency and prognostic value of MMR genes in STAD were conducted on the cBioPortal. The MLH1 co-expression network was established based on the LinkedOmics database. This study found that the expression of MSH2, MSH6 and PMS2 was up-regulated in STAD tissues. Moreover, differential MMR genetic expression levels were not significantly correlated with the clinical stages of STAD. Besides, no significant difference in PFS or OS was observed in STAD patients with or without MMR genetic alteration. Moreover, MLH1 and MSH2 were used to establish a prognostic risk model. The immune infiltration levels of most immune cells were upregulated in the high-risk group with elevated expression of PDCD1 and low TMB score. Finally, we found that MLH1 was an independent predictor of STAD prognosis among the four MMR genes. An MMR-related prognostic model for STAD was constructed based on genes. This model provides a new therapeutic concept for the diagnosis and treatment of STAD.https://doi.org/10.1038/s41598-024-84613-8Stomach adenocarcinomaMismatch repairMLH1MSH2Prognosis |
| spellingShingle | Zhihui Tian Lili Yang Rong Yang Wenhui Yang The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma Scientific Reports Stomach adenocarcinoma Mismatch repair MLH1 MSH2 Prognosis |
| title | The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma |
| title_full | The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma |
| title_fullStr | The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma |
| title_full_unstemmed | The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma |
| title_short | The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma |
| title_sort | prognostic and immunomodulatory role of the mmr system in patients with stomach adenocarcinoma |
| topic | Stomach adenocarcinoma Mismatch repair MLH1 MSH2 Prognosis |
| url | https://doi.org/10.1038/s41598-024-84613-8 |
| work_keys_str_mv | AT zhihuitian theprognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT liliyang theprognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT rongyang theprognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT wenhuiyang theprognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT zhihuitian prognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT liliyang prognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT rongyang prognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma AT wenhuiyang prognosticandimmunomodulatoryroleofthemmrsysteminpatientswithstomachadenocarcinoma |