Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2018; 24(43): 4950-4958
Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4950
Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke
Qi-Xiong Qin, Xue-Min Cheng, Li-Zhi Lu, Yun-Fei Wei, Da-Cheng Wang, Hai-Hua Li, Guo-Hui Li, Hong-Bin Liang, Sheng-Yu Li, Li Chen, Zhi-Jian Liang
Qi-Xiong Qin, Xue-Min Cheng, Li-Zhi Lu, Li Chen, Zhi-Jian Liang, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
Yun-Fei Wei, Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Province, China
Da-Cheng Wang, Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai 536000, Guangxi Province, China
Hai-Hua Li, Department of Neurology, Fusui County People’s Hospital, Chongzuo 532100, Guangxi Province, China
Guo-Hui Li, Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou 543002, Guangxi Province, China
Hong-Bin Liang, Department of Neurology, Cenxi People’s Hospital, Cenxi 543200, Guangxi Province, China
Sheng-Yu Li, Department of Neurology, Wuming County People’s Hospital, Nanning 530100, Guangxi Province, China
Author contributions: Qin QX and Liang ZJ conceived and designed the research; Qin QX collected the data and drafted the initial manuscript; Cheng XM and Lu LZ helped to analyze the data and write the article; Wei YF, Wang DC, Li HH, Li GH, Liang HB, and Li SY helped to collect the data; Chen L and Liang ZJ critically revised the manuscript; Liang ZJ provided financial support for this work; all authors read and approved the final manuscript.
Supported by the Guangxi Natural Science Foundation, No. 2015GXNSFAA139228 and No. 2016GXNSFAA380281; Guangxi Medical and Health and Appropriate Technology Development and Promotion Application Project, No. S201660; Innovation Project of Guangxi Graduate Education, No. YCSW2018105; and National Key Research and Development Program, No. 2018YFC1311300.
Institutional review board statement: This study was reviewed and approved by the First Affiliated Hospital of Guangxi Medical University Institutional Review Board.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent. For full disclosure, the details of the study are published on the home page of the First Affiliated Hospital of Guangxi Medical University.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Zhi-Jian Liang, MD, PhD, Professor, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi Province, China.
Telephone: +86-771-5330705
Received: September 4, 2018
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
Research background

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.

Research motivation

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.

Research objectives

The main objective of the retrospective study was to investigate the specific biomarkers and potential pathogenesis of CRCIS.

Research methods

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.

Research results

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%.

Research conclusions

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.

Research perspectives

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.