Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis
Objectives This study aimed to investigate the differentiation state and clinical significance of colorectal cancer cells, as well as to predict the immune response and prognosis of patients based on differentiation-related genes of colorectal cancer. Introduction Colorectal cancer cells exhibit dif...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-08-01
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| Series: | Cancer Control |
| Online Access: | https://doi.org/10.1177/10732748221121382 |
| _version_ | 1797838485534539776 |
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| author | Yuling Qin BS Meiqin Li MM Qiumei Lin BS Xiaolan Pan MM Yihua Liang BS Zhaodong Huang BS Zhimin Liu BS Lingsha Huang BM Min Fang MD |
| author_facet | Yuling Qin BS Meiqin Li MM Qiumei Lin BS Xiaolan Pan MM Yihua Liang BS Zhaodong Huang BS Zhimin Liu BS Lingsha Huang BM Min Fang MD |
| author_sort | Yuling Qin BS |
| collection | DOAJ |
| description | Objectives This study aimed to investigate the differentiation state and clinical significance of colorectal cancer cells, as well as to predict the immune response and prognosis of patients based on differentiation-related genes of colorectal cancer. Introduction Colorectal cancer cells exhibit different differentiation states under the influence of the tumor microenvironment, which determines the cell fates. Methods We combined single-cell sequencing (scRNA-seq) data from The Cancer Genome Atlas source with extensive transcriptome data from the Gene Expression Omnibus database. We obtained colorectal cancer differentiation-related genes using cell trajectory analysis and developed a colorectal cancer differentiation-related gene based molecular typing and prognostic model to predict the immune response and prognosis of patients with colorectal cancer. Results We identified 5 distinct cell differentiation subsets and 620 colorectal cancer differentiation-related genes. Colorectal cancer differentiation-related genes were significantly associated with metabolism, angiogenesis, and immunity. We separated patients into 3 subtypes based on colorectal cancer differentiation-related gene expression in the tumor and found differences among the different subtypes in immune infiltration status, immune checkpoint gene expression, clinicopathological features, and overall survival. Immunotherapeutic interventions involving a highly expressed immune checkpoint blockade may be selectively effective in the corresponding cancer subtypes. We built a risk score prediction model (5-year AUC: .729) consisting of the 4 most important predictors of survival (TIMP1, MMP1, LGALS4, and ITLN1). Finally, we generated and validated a nomogram consisting of the risk score and clinicopathological variables. Conclusion This study highlights the significance of genes involved in cell differentiation for clinical prognosis and immunotherapy in patients and provides prospective therapeutic targets for colorectal cancer. |
| first_indexed | 2024-04-09T15:41:35Z |
| format | Article |
| id | doaj.art-1776b020a86f4474a44ed272c40dde64 |
| institution | Directory Open Access Journal |
| issn | 1526-2359 |
| language | English |
| last_indexed | 2024-04-09T15:41:35Z |
| publishDate | 2022-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Control |
| spelling | doaj.art-1776b020a86f4474a44ed272c40dde642023-04-27T07:34:05ZengSAGE PublishingCancer Control1526-23592022-08-012910.1177/10732748221121382Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and PrognosisYuling Qin BSMeiqin Li MMQiumei Lin BSXiaolan Pan MMYihua Liang BSZhaodong Huang BSZhimin Liu BSLingsha Huang BMMin Fang MDObjectives This study aimed to investigate the differentiation state and clinical significance of colorectal cancer cells, as well as to predict the immune response and prognosis of patients based on differentiation-related genes of colorectal cancer. Introduction Colorectal cancer cells exhibit different differentiation states under the influence of the tumor microenvironment, which determines the cell fates. Methods We combined single-cell sequencing (scRNA-seq) data from The Cancer Genome Atlas source with extensive transcriptome data from the Gene Expression Omnibus database. We obtained colorectal cancer differentiation-related genes using cell trajectory analysis and developed a colorectal cancer differentiation-related gene based molecular typing and prognostic model to predict the immune response and prognosis of patients with colorectal cancer. Results We identified 5 distinct cell differentiation subsets and 620 colorectal cancer differentiation-related genes. Colorectal cancer differentiation-related genes were significantly associated with metabolism, angiogenesis, and immunity. We separated patients into 3 subtypes based on colorectal cancer differentiation-related gene expression in the tumor and found differences among the different subtypes in immune infiltration status, immune checkpoint gene expression, clinicopathological features, and overall survival. Immunotherapeutic interventions involving a highly expressed immune checkpoint blockade may be selectively effective in the corresponding cancer subtypes. We built a risk score prediction model (5-year AUC: .729) consisting of the 4 most important predictors of survival (TIMP1, MMP1, LGALS4, and ITLN1). Finally, we generated and validated a nomogram consisting of the risk score and clinicopathological variables. Conclusion This study highlights the significance of genes involved in cell differentiation for clinical prognosis and immunotherapy in patients and provides prospective therapeutic targets for colorectal cancer.https://doi.org/10.1177/10732748221121382 |
| spellingShingle | Yuling Qin BS Meiqin Li MM Qiumei Lin BS Xiaolan Pan MM Yihua Liang BS Zhaodong Huang BS Zhimin Liu BS Lingsha Huang BM Min Fang MD Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis Cancer Control |
| title | Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis |
| title_full | Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis |
| title_fullStr | Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis |
| title_full_unstemmed | Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis |
| title_short | Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis |
| title_sort | colorectal cancer cell differentiation trajectory predicts patient immunotherapy response and prognosis |
| url | https://doi.org/10.1177/10732748221121382 |
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