The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer
Abstract G2/M checkpoint and P53 pathway are essential in regulating the cell cycle and proliferation of cells, which is related to the progress of tumors. Here, we carried out an integrative analysis of the prognostic genes of these pathways in gastric cancer (GC) and thus developed a molecular sub...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-01472-7 |
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| author | Rishun Su Jia Chen Chen Dai Songcheng Yin Haoming Chen Xuezeng Sun Zhaoxin Fang Changhua Zhang Jingyao Chen Liang Gu |
| author_facet | Rishun Su Jia Chen Chen Dai Songcheng Yin Haoming Chen Xuezeng Sun Zhaoxin Fang Changhua Zhang Jingyao Chen Liang Gu |
| author_sort | Rishun Su |
| collection | DOAJ |
| description | Abstract G2/M checkpoint and P53 pathway are essential in regulating the cell cycle and proliferation of cells, which is related to the progress of tumors. Here, we carried out an integrative analysis of the prognostic genes of these pathways in gastric cancer (GC) and thus developed a molecular subtype. We identified prognostic differential expression genes (PDEGs) of G2/M checkpoint and P53 pathways between normal and tumor tissue in TCGA-STAD and developed a molecular subtype based on PDEGs. Meanwhile, the clinical significance of the molecular subtype was further explored. In addition, a comprehensive model and nomogram based on PDEGs score were constructed and validated by GSE26901 and GSE13861. Gastric cancer cell lines and patients’ specimens were used to validate the expression of selected genes.19 PDEGs were identified from these pathways in TCGA-STAD. Ulteriorly, a PDEGs score model consisting of 4 genes (PVT1, F2R, INCENP, IRAK1) was generated to classify patients into high- and low- PDEGs score subgroups. Patients in low PDEGs score groups had a better prognosis and a higher tumor mutational burden and may be more sensitive to chemotherapy and immunotherapy. Notably, the combination of PDEGs score and clinical features showed a pleasing survival prediction ability. In the GSE13861 cohort, the PDEGs score and its derivative model were confirmed with significant predictive effects in overall survival. Furthermore, these genes were significantly upregulated in both GC cell lines and tumor tissues and F2R was the hub gene resulting in poor survival. This paper has provided a distinct insight for tumor classification predicting prognosis more accurately and having the potential to instruct the use of chemotherapy and immunotherapy for patients with GC. |
| format | Article |
| id | doaj-art-35f78b8732504f44965c9840b2a8b8e6 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-35f78b8732504f44965c9840b2a8b8e62025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-01472-7The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancerRishun Su0Jia Chen1Chen Dai2Songcheng Yin3Haoming Chen4Xuezeng Sun5Zhaoxin Fang6Changhua Zhang7Jingyao Chen8Liang Gu9Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityZhongshan School of Medicine, Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Orthopedics, People’s Hospital of Yingde CityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityDigestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityAbstract G2/M checkpoint and P53 pathway are essential in regulating the cell cycle and proliferation of cells, which is related to the progress of tumors. Here, we carried out an integrative analysis of the prognostic genes of these pathways in gastric cancer (GC) and thus developed a molecular subtype. We identified prognostic differential expression genes (PDEGs) of G2/M checkpoint and P53 pathways between normal and tumor tissue in TCGA-STAD and developed a molecular subtype based on PDEGs. Meanwhile, the clinical significance of the molecular subtype was further explored. In addition, a comprehensive model and nomogram based on PDEGs score were constructed and validated by GSE26901 and GSE13861. Gastric cancer cell lines and patients’ specimens were used to validate the expression of selected genes.19 PDEGs were identified from these pathways in TCGA-STAD. Ulteriorly, a PDEGs score model consisting of 4 genes (PVT1, F2R, INCENP, IRAK1) was generated to classify patients into high- and low- PDEGs score subgroups. Patients in low PDEGs score groups had a better prognosis and a higher tumor mutational burden and may be more sensitive to chemotherapy and immunotherapy. Notably, the combination of PDEGs score and clinical features showed a pleasing survival prediction ability. In the GSE13861 cohort, the PDEGs score and its derivative model were confirmed with significant predictive effects in overall survival. Furthermore, these genes were significantly upregulated in both GC cell lines and tumor tissues and F2R was the hub gene resulting in poor survival. This paper has provided a distinct insight for tumor classification predicting prognosis more accurately and having the potential to instruct the use of chemotherapy and immunotherapy for patients with GC.https://doi.org/10.1038/s41598-025-01472-7Gastric cancerCell cyclePrognosisChemotherapyImmunotherapy |
| spellingShingle | Rishun Su Jia Chen Chen Dai Songcheng Yin Haoming Chen Xuezeng Sun Zhaoxin Fang Changhua Zhang Jingyao Chen Liang Gu The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer Scientific Reports Gastric cancer Cell cycle Prognosis Chemotherapy Immunotherapy |
| title | The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| title_full | The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| title_fullStr | The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| title_full_unstemmed | The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| title_short | The molecular subtype based on cell cycle-related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| title_sort | molecular subtype based on cell cycle related gene signature predicts the prognosis and chemotherapy and immunotherapy response in gastric cancer |
| topic | Gastric cancer Cell cycle Prognosis Chemotherapy Immunotherapy |
| url | https://doi.org/10.1038/s41598-025-01472-7 |
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