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
Processing time: 78 Days and 0.2 Hours

To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke (CRCIS).


A retrospective study was conducted on CRCIS patients (colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age- and sex- matched patients with colorectal cancer (CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS.


A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen (CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.001-1.003, P < 0.001], CEA levels (OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels (OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022 (95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%.


Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study.

Keywords: Colorectal cancer, Ischemic stroke, Biomarker, Pathogenesis

Core tip: Although cancer-related stroke has long been known, its biomarkers and underling pathogenesis are still unclear. It was hypothesized that a specific cancer type may affect the development of ischemic stroke (IS) according to its primary site, pathological type, and growth stage. It is reported that colorectal cancer can increase the risk of IS. We conducted a retrospective study on colorectal cancer-related IS (CRCIS) patients. We suggest that hypercoagulability induced by elevated carcinoembryonic antigen and increased neutrophil count are the main pathogenic factors in CRCIS, and the CRCIS Index, which serves as a biomarker of CRCIS, needs further study.