Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2019; 25(20): 2489-2502
Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2489
Prognostic significance of lymphovascular invasion in colorectal cancer and its association with genomic alterations
Hui-Hong Jiang, Zhi-Yong Zhang, Xiao-Yan Wang, Xuan Tang, Hai-Long Liu, Ai-Li Wang, Hua-Guang Li, Er-Jiang Tang, Mou-Bin Lin
Hui-Hong Jiang, Xuan Tang, Hai-Long Liu, Mou-Bin Lin, Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Hui-Hong Jiang, Xuan Tang, Ai-Li Wang, Hua-Guang Li, Er-Jiang Tang, Mou-Bin Lin, Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
Zhi-Yong Zhang, Department of General Surgery, Zhuji People’s Hospital of Zhejiang Province, Zhuji 311800, Zhejiang Province, China
Xiao-Yan Wang, Department of Emergency Surgery, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Ai-Li Wang, Hua-Guang Li, Er-Jiang Tang, Mou-Bin Lin, Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Author contributions: Lin MB and Tang EJ conceived and designed the study and are the co-corresponding authors; Zhang ZY, Wang XY, Tang X, Liu HL, and Wang AL helped collect the data and samples; Jiang HH performed the experiments; Jiang HH, Li HG, and Tang EJ analyzed and interpreted the data; Jiang HH drafted the manuscript.
Supported by: the National Natural Science Foundation of China, No. 81874201; and Shanghai Municipal Commission of Health and Family Planning, No. ZK2015A32 and No. 201840359.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Yangpu Hospital, Tongji University School of Medicine.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Er-Jiang Tang, MSc, Statistician, Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, No. 450 Tengyue Road, Shanghai 200090, China. tangerjiang1988051@163.com
Telephone: +86-21-55669260 Fax: +86-21-65696249
Received: February 2, 2019
Peer-review started: February 6, 2019
First decision: March 14, 2019
Revised: March 27, 2019
Accepted: April 19, 2019
Article in press: April 20, 2019
Published online: May 28, 2019
Processing time: 116 Days and 5 Hours
Abstract
BACKGROUND

Lymphovascular invasion (LVI) is suggested to be an early and important step in tumor progression toward metastasis, but its prognostic value and genetic mechanisms in colorectal cancer (CRC) have not been well investigated.

AIM

To investigate the prognostic value of LVI in CRC and identify the associated genomic alterations.

METHODS

We performed a retrospective analysis of 1219 CRC patients and evaluated the prognostic value of LVI for overall survival by the Kaplan-Meier method and multivariate Cox regression analysis. We also performed an array-based comparative genomic hybridization analysis of 47 fresh CRC samples to examine the genomic alterations associated with LVI. A decision tree model was applied to identify special DNA copy number alterations (DCNAs) for differentiating between CRCs with and without LVI. Functional enrichment and protein-protein interaction network analyses were conducted to explore the potential molecular mechanisms of LVI.

RESULTS

LVI was detected in 150 (12.3%) of 1219 CRCs, and the presence was positively associated with higher histological grade and advanced tumor stage (both P < 0.001). Compared with the non-LVI group, the LVI group showed a 1.77-fold (95% confidence interval: 1.40-2.25, P < 0.001) increased risk of death and a significantly lower 5-year overall survival rate (P < 0.001). Based on the comparative genomic hybridization data, 184 DCNAs (105 gains and 79 losses) were identified to be significantly related to LVI (P < 0.05), and the majority were located at 22q, 17q, 10q, and 6q. We further constructed a decision tree classifier including seven special DCNAs, which could distinguish CRCs with LVI from those without it at an accuracy of 95.7%. Functional enrichment and protein-protein interaction network analyses revealed that the genomic alterations related to LVI were correlated with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.

CONCLUSION

LVI is an independent predictor for survival in CRC, and its development may correlate with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.

Keywords: Colorectal cancer; Lymphovascular invasion; Prognostic; DNA copy number aberration; Functional analysis

Core tip: Lymphovascular invasion (LVI) is suggested to be an obligatory step in tumor progression toward metastasis, but its genetic mechanisms in colorectal cancer (CRC) have not been fully understood. This study showed that LVI was significantly associated with features of aggressive tumors and reduced survival in CRC, and its development might correlate with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling. We also constructed a DNA copy number alteration classifier that could estimate the LVI status with high accuracy, which might contribute to the management of CRC.