Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma
Abstract Stomach adenocarcinoma (STAD) is the third leading cause of cancer-related deaths and the fifth most prevalent malignancy worldwide. Mitochondrial respiratory chain complexes play a crucial role in STAD pathogenesis. However, how mitochondrial respiratory chain complex genes (MRCCGs) affect...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-02913-x |
| _version_ | 1797845750013493248 |
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| author | Jing Yang Feifan Jin Huanjuan Li Yuhuan Shen Weilin Shi Lina Wang Lei Zhong Gongqiang Wu Qiaoliang Wu Yanchun Li |
| author_facet | Jing Yang Feifan Jin Huanjuan Li Yuhuan Shen Weilin Shi Lina Wang Lei Zhong Gongqiang Wu Qiaoliang Wu Yanchun Li |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | Abstract Stomach adenocarcinoma (STAD) is the third leading cause of cancer-related deaths and the fifth most prevalent malignancy worldwide. Mitochondrial respiratory chain complexes play a crucial role in STAD pathogenesis. However, how mitochondrial respiratory chain complex genes (MRCCGs) affect the prognosis and tumor microenvironment in STAD remains unclear. In this study, we systematically analyzed genetic alterations and copy number variations of different expression densities of MRCCGs, based on 806 samples from two independent STAD cohorts. Then we employed the unsupervised clustering method to classify the samples into three expression patterns based on the prognostic MRCCG expressions, and found that they were involved in different biological pathways and correlated with the clinicopathological characteristics, immune cell infiltration, and prognosis of STAD. Subsequently, we conducted a univariate Cox regression analysis to identify the prognostic value of 1175 subtype-related differentially expressed genes (DEGs) and screened out 555 prognostic-related genes. Principal component analysis was performed and developed the MG score system to quantify MRCCG patterns of STAD. The prognostic significance of MG Score was validated in three cohorts. The low MG score group, characterized by increased microsatellite instability-high (MSI-H), tumor mutation burden (TMB), PD-L1 expression, had a better prognosis. Interestingly, we demonstrated MRCCG patterns score could predict the sensitivity to ferroptosis inducing therapy. Our comprehensive analysis of MRCCGs in STAD demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. Our findings highlight that MRCCGs may provide a new understanding of immunotherapy strategies for gastric cancer and provide a new perspective on the development of personalized immune therapeutic strategies for patients with STAD. |
| first_indexed | 2024-04-09T17:43:58Z |
| format | Article |
| id | doaj.art-76c600e532e74d69916c3fbc46573090 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-09T17:43:58Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-76c600e532e74d69916c3fbc465730902023-04-16T11:25:54ZengBMCCancer Cell International1475-28672023-04-0123112110.1186/s12935-023-02913-xIdentification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinomaJing Yang0Feifan Jin1Huanjuan Li2Yuhuan Shen3Weilin Shi4Lina Wang5Lei Zhong6Gongqiang Wu7Qiaoliang Wu8Yanchun Li9Laboratory Medicine Center, Department of Laboratory Medicine, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical CollegeCenter for Plastic & Reconstructive Surgery, Department of Stomatology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical CollegeLaboratory Medicine Center, Department of Laboratory Medicine, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical CollegeLaboratory Medicine Center, Department of Laboratory Medicine, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical CollegeDepartment of Medicine, Taizhou Luqiao District Second People’s HospitalDepartment of Medicine, Taizhou Luqiao District Second People’s HospitalDepartment of Clinical Laboratory, Tongxiang Hospital of Traditional Chinese MedicineDepartment of Hematology, Dongyang People’s Hospital, Dongyang Hospital Affiliated to Wenzhou Medical UniversityDepartment of Hematology, Jiashan first people’s HospitalDepartment of Central Laboratory, Affiliated Hangzhou first people’s Hospital, Zhejiang University School of MedicineAbstract Stomach adenocarcinoma (STAD) is the third leading cause of cancer-related deaths and the fifth most prevalent malignancy worldwide. Mitochondrial respiratory chain complexes play a crucial role in STAD pathogenesis. However, how mitochondrial respiratory chain complex genes (MRCCGs) affect the prognosis and tumor microenvironment in STAD remains unclear. In this study, we systematically analyzed genetic alterations and copy number variations of different expression densities of MRCCGs, based on 806 samples from two independent STAD cohorts. Then we employed the unsupervised clustering method to classify the samples into three expression patterns based on the prognostic MRCCG expressions, and found that they were involved in different biological pathways and correlated with the clinicopathological characteristics, immune cell infiltration, and prognosis of STAD. Subsequently, we conducted a univariate Cox regression analysis to identify the prognostic value of 1175 subtype-related differentially expressed genes (DEGs) and screened out 555 prognostic-related genes. Principal component analysis was performed and developed the MG score system to quantify MRCCG patterns of STAD. The prognostic significance of MG Score was validated in three cohorts. The low MG score group, characterized by increased microsatellite instability-high (MSI-H), tumor mutation burden (TMB), PD-L1 expression, had a better prognosis. Interestingly, we demonstrated MRCCG patterns score could predict the sensitivity to ferroptosis inducing therapy. Our comprehensive analysis of MRCCGs in STAD demonstrated their potential roles in the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. Our findings highlight that MRCCGs may provide a new understanding of immunotherapy strategies for gastric cancer and provide a new perspective on the development of personalized immune therapeutic strategies for patients with STAD.https://doi.org/10.1186/s12935-023-02913-xStomach adenocarcinomaMitochondrial complexesTumor microenvironmentMicrosatellite instabilityPrognosis |
| spellingShingle | Jing Yang Feifan Jin Huanjuan Li Yuhuan Shen Weilin Shi Lina Wang Lei Zhong Gongqiang Wu Qiaoliang Wu Yanchun Li Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma Cancer Cell International Stomach adenocarcinoma Mitochondrial complexes Tumor microenvironment Microsatellite instability Prognosis |
| title | Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| title_full | Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| title_fullStr | Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| title_full_unstemmed | Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| title_short | Identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| title_sort | identification of mitochondrial respiratory chain signature for predicting prognosis and immunotherapy response in stomach adenocarcinoma |
| topic | Stomach adenocarcinoma Mitochondrial complexes Tumor microenvironment Microsatellite instability Prognosis |
| url | https://doi.org/10.1186/s12935-023-02913-x |
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