CXCR4 mRNA overexpression: an indicator of poor survival and predictor of response to immune checkpoint inhibitors in patients with metastatic colorectal cancer.
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
환자: metastatic CRC with mismatch repair deficient (dMMR) tumours (<10%) are eligible for immune checkpoint blockade (ICB)
I · Intervention 중재 / 시술
추출되지 않음
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
Remarkably, high expression was associated with improved survival in all ICB-treated patients. [CONCLUSION] Correlation of high expression with changes in the TME and improved outcomes following ICB suggests its potential for selecting immunotherapeutic strategies in CRC.
[OBJECTIVE] Expression of CXC-chemokine receptor 4 (CXCR4) is associated with poor prognosis in colorectal cancer (CRC), metastasis and immune cell infiltration.
- p-value p<0.001
- 95% CI 0.86 to 0.99
APA
Gholami S, Saeed A, et al. (2026). CXCR4 mRNA overexpression: an indicator of poor survival and predictor of response to immune checkpoint inhibitors in patients with metastatic colorectal cancer.. BMJ oncology, 5(1), e001003. https://doi.org/10.1136/bmjonc-2025-001003
MLA
Gholami S, et al.. "CXCR4 mRNA overexpression: an indicator of poor survival and predictor of response to immune checkpoint inhibitors in patients with metastatic colorectal cancer.." BMJ oncology, vol. 5, no. 1, 2026, pp. e001003.
PMID
41948196
Abstract
[OBJECTIVE] Expression of CXC-chemokine receptor 4 (CXCR4) is associated with poor prognosis in colorectal cancer (CRC), metastasis and immune cell infiltration. Currently, only patients with metastatic CRC with mismatch repair deficient (dMMR) tumours (<10%) are eligible for immune checkpoint blockade (ICB).
[METHODS AND ANALYSIS] 15 026 CRC tumour samples were analysed at Caris Life Sciences using whole-exome sequencing, whole-transcriptome sequencing and immunohistochemistry (IHC). This was a retrospective analysis in which all consecutive CRC cases between 2008 and 2023 with available molecular profiling and survival data were included. To elucidate the role of mRNA expression in the tumour microenvironment (TME) and response to ICB, CRC samples were stratified by high and low quartiles of mRNA expression levels and compared for molecular and clinical characteristics. Tumour mutational burden [TMB) and dMMR status were determined from DNA sequencing data. Immune cell infiltration was calculated from deconvolution of bulk RNA sequencing data. PD-L1 expression was determined by IHC stain intensity. Information for real-world survival and pembrolizumab treatment was obtained from the CODEai database using insurance claims-based data.Overall survival was calculated from date of either first specimen collection or treatment to last of healthcare contact with HR and p value calculated using the Cox proportional hazards model and log-rank test, respectively.
[RESULTS] Metastatic sites showed higher expression than primary tumours (22.7 vs 18.6 median transcripts per million [TPM], p<0.001). expression was lower in liver than non-liver metastases (21.2 vs 24.8 TPM, p<0.001). Median mRNA expression was positively associated with high TMB, dMMR and positive PD-L1 status. High expression was associated with tumours with higher infiltration of B cells and M1/M2 macrophages. High expression in the primary tumour was associated with worse prognosis (HR 0.92, 95% CI 0.86 to 0.99, p<0.02), regardless of dMMR status. In metastatic tumours, high mRNA expression correlated with improved survival (HR 1.12, 95% CI 1.04 to 1.20, p=0.003). Remarkably, high expression was associated with improved survival in all ICB-treated patients.
[CONCLUSION] Correlation of high expression with changes in the TME and improved outcomes following ICB suggests its potential for selecting immunotherapeutic strategies in CRC.
[METHODS AND ANALYSIS] 15 026 CRC tumour samples were analysed at Caris Life Sciences using whole-exome sequencing, whole-transcriptome sequencing and immunohistochemistry (IHC). This was a retrospective analysis in which all consecutive CRC cases between 2008 and 2023 with available molecular profiling and survival data were included. To elucidate the role of mRNA expression in the tumour microenvironment (TME) and response to ICB, CRC samples were stratified by high and low quartiles of mRNA expression levels and compared for molecular and clinical characteristics. Tumour mutational burden [TMB) and dMMR status were determined from DNA sequencing data. Immune cell infiltration was calculated from deconvolution of bulk RNA sequencing data. PD-L1 expression was determined by IHC stain intensity. Information for real-world survival and pembrolizumab treatment was obtained from the CODEai database using insurance claims-based data.Overall survival was calculated from date of either first specimen collection or treatment to last of healthcare contact with HR and p value calculated using the Cox proportional hazards model and log-rank test, respectively.
[RESULTS] Metastatic sites showed higher expression than primary tumours (22.7 vs 18.6 median transcripts per million [TPM], p<0.001). expression was lower in liver than non-liver metastases (21.2 vs 24.8 TPM, p<0.001). Median mRNA expression was positively associated with high TMB, dMMR and positive PD-L1 status. High expression was associated with tumours with higher infiltration of B cells and M1/M2 macrophages. High expression in the primary tumour was associated with worse prognosis (HR 0.92, 95% CI 0.86 to 0.99, p<0.02), regardless of dMMR status. In metastatic tumours, high mRNA expression correlated with improved survival (HR 1.12, 95% CI 1.04 to 1.20, p=0.003). Remarkably, high expression was associated with improved survival in all ICB-treated patients.
[CONCLUSION] Correlation of high expression with changes in the TME and improved outcomes following ICB suggests its potential for selecting immunotherapeutic strategies in CRC.