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
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. It has been reported that many clinicopathological factors may contribute to the prognostic prediction of cancer patients except tumor-node-metastasis stage, including lymphovascular invasion (LVI). LVI is suggested to be an early and critical step in lymph node metastasis and systemic dissemination of cancer cells. However, the prognostic value and genetic mechanisms of LVI in CRC have not been well investigated so far.

Research motivation

LVI is a common histopathological finding in cancers and is considered to be an important step in cancer progression toward metastasis, but its genetic mechanisms in CRC have yet to be fully understood. Our study may offer new insight into the biology of LVI and provide valuable information for better management of CRC.

Research objectives

The objective of this study was to investigate the prognostic value of LVI in CRC and identify the genomic alterations associated with LVI using array-based comparative genomic hybridization (CGH).

Research methods

We performed a retrospective analysis in a population of 1219 CRC patients to evaluate the presence of LVI, as well as its relationship with classical clinicopathological parameters and patient’s outcome. Kaplan-Meier method and Cox regression model were used for overall survival analysis. We also analyzed the genomic profiles of 47 CRC samples using CGH to identify the genomic alterations associated with LVI. A decision tree model classifier was applied to the CGH data to identify special DNA copy number alterations (DCNAs) for differentiating CRCs with and without LVI. We further performed functional enrichment and protein-protein interaction network analyses to explore the potential molecular mechanisms of LVI in CRC.

Research results

Of the 1219 CRC patients included in the retrospective analysis, 150 (12.3%) cases presented with LVI. The comparison of clinicopathological characteristics between CRCs with and without LVI found that the presence of LVI was significantly with higher histological grade and advanced tumor stage (both P < 0.001). Survival analysis showed that LVI was an independent predictor for overall survival in CRC, with a hazard ratio of 1.77 (95% confidence interval: 1.40-2.25, P < 0.001). Based on the CGH data of 47 CRC samples, 184 DCNAs (105 gains and 79 losses) were found to exhibit a significant difference in the frequencies between LVI and non-LVI groups (P < 0.05), and the majority were located at 22q, 17q, 10q, and 6q. We further performed decision tree analysis and constructed a classifier that could distinguish CRCs with LVI from those without it at an accuracy of 95.7% by examining seven special DCNAs. Functional enrichment analyses showed that the genomic alterations related to LVI were correlated with immune response and inflammation. Additionally, we constructed a protein-protein interaction network and screened out some key genes, such as EP300, STAT3, SIRT1, and RPS6KB1, which were involved in epithelial-mesenchymal transition, active angiogenesis or matrix remodeling.

Research conclusions

The present study identified 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.

Research perspectives

Our study preliminarily explored the genetic alterations associated with LVI in CRC, which might offer novel targets for the treatment and prevention of cancer dissemination. Further studies are required to confirm our findings and to clarify the precise mechanism involved in LVI.