Predicting mechanism of immune response in microsatellite instability colorectal cancer
Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different ch...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024041513 |
| _version_ | 1797224158051958784 |
|---|---|
| author | Peng Sun Yusong Luan Xuhao Cai Qi Liu Peide Ren Pengpan Xin Yonggang Yu Bolun Song Yangyang Wang Huijing Chang Haoyue Ma Yinggang Chen |
| author_facet | Peng Sun Yusong Luan Xuhao Cai Qi Liu Peide Ren Pengpan Xin Yonggang Yu Bolun Song Yangyang Wang Huijing Chang Haoyue Ma Yinggang Chen |
| author_sort | Peng Sun |
| collection | DOAJ |
| description | Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines. Notably, three MSI specific recurring modules were identified by non-negative matrix factorization (NMF). High NMF score genes enriched in the function of metabolism and inflammatory response. Focusing on top specific active transcription factor (TF), RUNX3 (Runt-related transcription factor 3), our results suggest that T cell infiltration was increased in RUNX3 high MSI CRC samples. Unbiased Gene Set Enrichment Analysis (GSEA) showed that RUNX3 was strongly associated with immune and metastasis related functions, such as Interferon Gamma (IFN-γ) and EPITHELIAL MESENCHYMAL TRANSITION (EMT). In addition, RUNX3 shows specific highly activated at epigenetic level in MSI compared with other gastrointestinal carcinomas. Positive correlation between RUNX3 and most immune checkpoints further confirmed RUNX3 might have crucial roles in MSI cancer progression and immunotherapy. Taken together, these results indicate significant tumor heterogeneity of two CRC subtypes at single-cell level and epigenetic modification level. These results also linked transcriptional dysregulation with immune infiltration at single-cell level in MSI, which may advance the application of scRNA-Seq technology in immunotherapy and contribute to developing novel biomarkers of this malignancy. |
| first_indexed | 2024-04-24T13:48:40Z |
| format | Article |
| id | doaj.art-cda8ecfee7aa42778dc04d4845822ffb |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:48:40Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-cda8ecfee7aa42778dc04d4845822ffb2024-04-04T05:06:52ZengElsevierHeliyon2405-84402024-03-01106e28120Predicting mechanism of immune response in microsatellite instability colorectal cancerPeng Sun0Yusong Luan1Xuhao Cai2Qi Liu3Peide Ren4Pengpan Xin5Yonggang Yu6Bolun Song7Yangyang Wang8Huijing Chang9Haoyue Ma10Yinggang Chen11Department of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaDepartment of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaCorresponding author.; Department of Gastrointestinal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, ChinaColorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines. Notably, three MSI specific recurring modules were identified by non-negative matrix factorization (NMF). High NMF score genes enriched in the function of metabolism and inflammatory response. Focusing on top specific active transcription factor (TF), RUNX3 (Runt-related transcription factor 3), our results suggest that T cell infiltration was increased in RUNX3 high MSI CRC samples. Unbiased Gene Set Enrichment Analysis (GSEA) showed that RUNX3 was strongly associated with immune and metastasis related functions, such as Interferon Gamma (IFN-γ) and EPITHELIAL MESENCHYMAL TRANSITION (EMT). In addition, RUNX3 shows specific highly activated at epigenetic level in MSI compared with other gastrointestinal carcinomas. Positive correlation between RUNX3 and most immune checkpoints further confirmed RUNX3 might have crucial roles in MSI cancer progression and immunotherapy. Taken together, these results indicate significant tumor heterogeneity of two CRC subtypes at single-cell level and epigenetic modification level. These results also linked transcriptional dysregulation with immune infiltration at single-cell level in MSI, which may advance the application of scRNA-Seq technology in immunotherapy and contribute to developing novel biomarkers of this malignancy.http://www.sciencedirect.com/science/article/pii/S2405844024041513Colorectal cancerMicrosatellite instabilitySingle cell RNA-SeqRUNX3Immune infiltrationEPITHELIAL MESENCHYMAL TRANSITION |
| spellingShingle | Peng Sun Yusong Luan Xuhao Cai Qi Liu Peide Ren Pengpan Xin Yonggang Yu Bolun Song Yangyang Wang Huijing Chang Haoyue Ma Yinggang Chen Predicting mechanism of immune response in microsatellite instability colorectal cancer Heliyon Colorectal cancer Microsatellite instability Single cell RNA-Seq RUNX3 Immune infiltration EPITHELIAL MESENCHYMAL TRANSITION |
| title | Predicting mechanism of immune response in microsatellite instability colorectal cancer |
| title_full | Predicting mechanism of immune response in microsatellite instability colorectal cancer |
| title_fullStr | Predicting mechanism of immune response in microsatellite instability colorectal cancer |
| title_full_unstemmed | Predicting mechanism of immune response in microsatellite instability colorectal cancer |
| title_short | Predicting mechanism of immune response in microsatellite instability colorectal cancer |
| title_sort | predicting mechanism of immune response in microsatellite instability colorectal cancer |
| topic | Colorectal cancer Microsatellite instability Single cell RNA-Seq RUNX3 Immune infiltration EPITHELIAL MESENCHYMAL TRANSITION |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024041513 |
| work_keys_str_mv | AT pengsun predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT yusongluan predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT xuhaocai predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT qiliu predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT peideren predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT pengpanxin predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT yonggangyu predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT bolunsong predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT yangyangwang predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT huijingchang predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT haoyuema predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer AT yinggangchen predictingmechanismofimmuneresponseinmicrosatelliteinstabilitycolorectalcancer |