Abstract
BACKGROUND: Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients' tumors for predicting clinical outcome. OBJECTIVE: To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset. METHODS: Chemokine (CXCL-12α, CXCL-12β, IL-17A, CXCL-8, GM-CSF) and chemokine receptor (CXCR-4, CXCR-7) transcripts were analyzed by RT-qPCR in 76 CRC specimens (normal: 27, tumor: 49; clinical cohort). RNA-Seq data was analyzed from the TCGA-dataset (n= 375). Transcript levels were correlated with outcome; analyses: univariate, multivariable, Kaplan-Meier. RESULTS: In the clinical cohort, chemokine/chemokine receptor levels were elevated 3-10-fold in CRC specimens (P 0.004) and were higher in patients who developed metastasis (P= 0.03-< 0.0001). CXCR-4, CXCR-7, CXCL-12α, CXCL-8, IL-17 and GM-CSF levels predicted metastasis (P 0.0421) and/or overall survival (OS; P 0.0373). The CXCR-4+CXCR-7+CXCL-12 marker (CXCR-4/7+CXCL-12 (α/b) signature) stratified patients into risk for metastasis (P= 0.0014; OR, 2.72) and OS (P= 0.0442; OR, 2.7); sensitivity: 86.67%, specificity: 97.06%. In the TCGA-dataset, the CXCR-4/7+CXCL-12 signature predicted metastasis (P= 0.011; OR, 2.72) and OS (P= 0.0006; OR: 4.04). In both datasets, the signature was an independent predictor of clinical outcome. CONCLUSIONS: Results of 451 specimens from both cohorts reveal that the CXCR-4/7+CXCL-12 signature potentially predicts outcome in CRC patients and may allow earlier intervention.
Original language | English (US) |
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Pages (from-to) | 291-301 |
Number of pages | 11 |
Journal | Cancer Biomarkers |
Volume | 26 |
Issue number | 3 |
DOIs | |
State | Published - Nov 1 2019 |
Keywords
- CXCL-12
- CXCL-8
- CXCR-4
- CXCR-7
- colorectal cancer
ASJC Scopus subject areas
- Genetics
- Oncology
- Cancer Research