Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights
BackgroundColorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509658/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846136305381015552 |
|---|---|
| author | Quanjun Lin Zhiqiang Wang Jue Wang Ming Xu Xinyi Zhang Peng Sun Yihang Yuan |
| author_facet | Quanjun Lin Zhiqiang Wang Jue Wang Ming Xu Xinyi Zhang Peng Sun Yihang Yuan |
| author_sort | Quanjun Lin |
| collection | DOAJ |
| description | BackgroundColorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.MethodsWe utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.ResultsEight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.ConclusionIn summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC. |
| format | Article |
| id | doaj-art-24b8005060f94fa782b26d9a8b4e5168 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-24b8005060f94fa782b26d9a8b4e51682024-12-09T06:28:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15096581509658Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insightsQuanjun Lin0Zhiqiang Wang1Jue Wang2Ming Xu3Xinyi Zhang4Peng Sun5Yihang Yuan6Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinical Medical College, Southwest Medical University, Luzhou, ChinaDepartment of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundColorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.MethodsWe utilized single-cell RNA sequencing technology to analyze 13 tissue samples from 4 CRC patients, identifying key cell types within the tumor microenvironment. Intercellular communication was assessed using CellChat, and a risk score model was developed based on eight prognostic genes to enhance patient stratification for immunotherapeutic approaches. Additionally, in vitro experiments were performed on DLX2, a gene strongly associated with poor prognosis, to validate its potential role as a therapeutic target in CRC progression.ResultsEight major cell types were identified across the tissue samples. Within the tumor cell population, seven distinct subtypes were recognized, with the C0 FXYD5+ tumor cells subtype being significantly linked to cancer progression and poor prognosis. CellChat analysis indicated extensive communication among tumor cells, fibroblasts, and immune cells, underscoring the complexity of the tumor microenvironment. The risk score model demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates in CRC patients. Enrichment analysis revealed that the C0 FXYD5+ tumor cell subtype exhibited increased energy metabolism, protein synthesis, and oxidative phosphorylation, contributing to its aggressive behavior. In vitro experiments confirmed DLX2 as a critical gene associated with poor prognosis, suggesting its viability as a target for improving drug sensitivity.ConclusionIn summary, this study advances our understanding of CRC progression by identifying critical tumor subtypes, molecular pathways, and prognostic markers that can inform innovative strategies for predicting and enhancing drug sensitivity. These findings hold promise for optimizing immunotherapeutic approaches and developing new targeted therapies, ultimately aiming to improve patient outcomes in CRC.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509658/fullcolorectal cancer (CRC)single-cell RNA sequencing (scRNA-seq)tumor cell subtypesFXYD5+ Tumor Risk Score (FTRS)energy metabolism in cancer |
| spellingShingle | Quanjun Lin Zhiqiang Wang Jue Wang Ming Xu Xinyi Zhang Peng Sun Yihang Yuan Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights Frontiers in Immunology colorectal cancer (CRC) single-cell RNA sequencing (scRNA-seq) tumor cell subtypes FXYD5+ Tumor Risk Score (FTRS) energy metabolism in cancer |
| title | Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| title_full | Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| title_fullStr | Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| title_full_unstemmed | Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| title_short | Innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| title_sort | innovative strategies to optimise colorectal cancer immunotherapy through molecular mechanism insights |
| topic | colorectal cancer (CRC) single-cell RNA sequencing (scRNA-seq) tumor cell subtypes FXYD5+ Tumor Risk Score (FTRS) energy metabolism in cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509658/full |
| work_keys_str_mv | AT quanjunlin innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT zhiqiangwang innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT juewang innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT mingxu innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT xinyizhang innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT pengsun innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights AT yihangyuan innovativestrategiestooptimisecolorectalcancerimmunotherapythroughmolecularmechanisminsights |