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| Content Provider | frontiers |
|---|---|
| Author | Pan, Bei Yue, Yanzhe Ding, Wenbo Sun, Li Xu, Mu Wang, Shukui |
| Description | Metastasis is the most common cause of death of colorectal cancer (CRC), and the essential role of immune microenvironment in colorectal cancer metastasis is of great attention. We used single-sample gene set enrichment analysis (ssGSEA) to assess the immune infiltration of the TCGA-CRC transcriptome and classified patients into high, medium and low groups. Subsequently, based on the normal/tumor, high/low immune cell infiltration group and metastatic/non-metastatic group, we identified 161 differentially expressed genes and performed random assignment. Using Lasso regression analysis, we constructed a prognostic model containing 3 metastasis- and immune- related gene pairs and validated its efficiency in four independent CRC cohorts. It was further evaluated in terms of clinicopathological features, tumor-infiltrating immune cells, and chemotherapy and targeted drug sensitivity. In addition, fatty acid binding protein 4 (FABP4) and cathepsin W (CTSW) derived from the constitutive model were explored and identified to be involved in metastasis and immunity of CRC. In conclusion, a validated prognosis predictive model for CRC was constructed. CTSW and FABP4 are potential targets for CRC treatment. |
| Abstract | BackgroundMetastasis remains the leading cause of mortality in patients diagnosed with colorectal cancer (CRC). The pivotal contribution of the immune microenvironment in the initiation and progression of CRC metastasis has gained significant attention.MethodsA total of 453 CRC patients from The Cancer Genome Atlas (TCGA) were included as the training set, and GSE39582, GSE17536, GSE29621, GSE71187 were included as the validation set. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the immune infiltration of patients. Least absolute shrinkage and selection operator (LASSO) regression analysis, Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier analysis were used to construct and validate risk models based on R package. CTSW and FABP4-knockout CRC cells were constructed via CRISPR-Cas9 system. Western-blot and Transwell assay were utilized to explore the role of fatty acid binding protein 4 (FABP4) / cathepsin W (CTSW) in CRC metastasis and immunity.ResultsBased on the normal/tumor, high-/low-immune cell infiltration, and metastatic/non-metastatic group, we identified 161 differentially expressed genes. After random assignment and LASSO regression analysis, a prognostic model containing 3 metastasis- and immune-related gene pairs was constructed and represented good prognostic prediction efficiency in the training set and 4 independent CRC cohorts. According to this model, we clustered patients and found that the high-ris... |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2023.1161382 |
| Volume Number | 14 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2023-04-26 |
| Access Restriction | Open |
| Subject Keyword | Gene pair Colorecal cancer Immunity Metastasis Prognostic model |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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