Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4950
Peer-review started: September 4, 2018
First decision: October 24, 2018
Revised: November 2, 2018
Accepted: November 8, 2018
Article in press: November 8, 2018
Published online: November 21, 2018
Processing time: 78 Days and 0.2 Hours
Cancer is associated with an increased risk of ischemic stroke (IS), and IS can be the first manifestation of an occult cancer. Several biomarkers and mechanisms in cancer related-IS have been reported. However, most previous studies had been conducted on several types of cancer with few studies focusing on one cancer. The specific biomarkers and mechanisms of colorectal cancer related-IS (CRCIS) have not been fully investigated yet. Therefore, the aim of the study was to investigate the specific biomarkers and potential pathogenesis of CRCIS, which may contribute to the establishment of CRCIS therapeutic strategy.
Cancer related-IS has received widespread attention. However, biomarkers and the pathogenesis of CRCIS remain unclear. The key problems to be solved are how to identify CRCIS patients in clinical practice and whether hypercoagulability is the major cause and mechanism of IS. Identifying the biomarkers of CRCIS patients, which combined with clinical manifestation may be helpful to distinguish patients with other stroke etiology and other types of cancer-related stroke. Understanding the specific mechanisms in stroke of CRC patients is crucial to its therapeutic strategy.
The main objective of the retrospective study was to investigate the specific biomarkers and potential pathogenesis of CRCIS.
The clinical data of 114 CRC patients with IS but without conventional stroke risk factors were retrospectively analyzed and compared with those of CRC patients without IS. Univariate and multivariate analyses were used to identify independent risk factors for CRCIS. The products of the independent risk factors in the two groups were calculated. The receiver operator characteristic curve was used to determine the area under the curve and the optimal value of the products.
Our study found that multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). In addition, the level of plasma D-dimer, neutrophil count, carcinoembryonic antigen (CEA), and cancer antigen 125 were significantly higher in CRCIS patients compared to CRC patients. D-dimer, neutrophil count, and CEA were found to independently associated with CRCIS. Considering that the combined effects of D-dimer, neutrophil count, and CEA may be the major cause of hypercoagulability, the products of each were calculated. The area under the curve of the product was 0.889 ± 0.022, optimal cut-off value of the product was 252.06, which was called the CRCIS Index in the study, with a sensitivity of 86.0% and specificity of 79.8%.
Neutrophil extracellular traps generated from active neutrophils and CEA secreted by CRC cells that resulted in hypercoagulability may be the major cause of CRCIS. The CRCIS index, which serves as a biomarker for CRCIS, may need to be confirmed by future studies.
In the future, the detailed mechanism of hypercoagulability in CRCIS patients may need to further illuminated. The CRCIS index that serves as a useful biomarker for the identification of CRCIS should be confirmed in larger prospective population studies.