Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer
Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patie...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037024000266 |
| _version_ | 1797303374013530112 |
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| author | Jie Li Tian Yu Juan Sun Mingwei Ma Zicheng Zheng Weiming Kang Xin Ye |
| author_facet | Jie Li Tian Yu Juan Sun Mingwei Ma Zicheng Zheng Weiming Kang Xin Ye |
| author_sort | Jie Li |
| collection | DOAJ |
| description | Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients. |
| first_indexed | 2024-03-07T23:51:49Z |
| format | Article |
| id | doaj.art-330bffe28b1046c9950af109af29267b |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-03-07T23:51:49Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-330bffe28b1046c9950af109af29267b2024-02-19T04:13:22ZengElsevierComputational and Structural Biotechnology Journal2001-03702024-12-01239901004Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancerJie Li0Tian Yu1Juan Sun2Mingwei Ma3Zicheng Zheng4Weiming Kang5Xin Ye6Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaCorrespondence authors.; Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaCorrespondence authors.; Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifu Yuan, Dongcheng District, 100730 Beijing, People’s Republic of ChinaCell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.http://www.sciencedirect.com/science/article/pii/S2001037024000266Cell pyroptosisGastric cancerSingle-cell RNA sequencingImmune infiltrationPrognostic signature |
| spellingShingle | Jie Li Tian Yu Juan Sun Mingwei Ma Zicheng Zheng Weiming Kang Xin Ye Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer Computational and Structural Biotechnology Journal Cell pyroptosis Gastric cancer Single-cell RNA sequencing Immune infiltration Prognostic signature |
| title | Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer |
| title_full | Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer |
| title_fullStr | Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer |
| title_full_unstemmed | Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer |
| title_short | Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer |
| title_sort | comprehensive integration of single cell rna and transcriptome rna sequencing to establish a pyroptosis related signature for improving prognostic prediction of gastric cancer |
| topic | Cell pyroptosis Gastric cancer Single-cell RNA sequencing Immune infiltration Prognostic signature |
| url | http://www.sciencedirect.com/science/article/pii/S2001037024000266 |
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