Case Control Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2024; 16(3): 670-686
Published online Mar 15, 2024. doi: 10.4251/wjgo.v16.i3.670
Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer
Ye Yang, Wu Wen, Feng-Lin Chen, Ying-Jie Zhang, Xiao-Cong Liu, Xiao-Yan Yang, Shan-Shan Hu, Ye Jiang, Jing Yuan
Ye Yang, Digestive Diseases, Chengdu Qingbaijiang District People's Hospital, Chengdu 610300, Sichuan Province, China
Wu Wen, Ying-Jie Zhang, Xiao-Cong Liu, Xiao-Yan Yang, Shan-Shan Hu, Ye Jiang, Jing Yuan, Digestive Diseases, Chengdu Second People’s Hospital, Chengdu 610000, Sichuan Province, China
Feng-Lin Chen, Graduate School, Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Author contributions: Wen W proposed and designed the project, provided scientific research funds, and coordinated and contacted various matters related to the pathology department; Zhang YJ, Liu XC and Yang XY collected the pathological specimens; Hu SS, Jiang Y and Yuan J performed the collection of patient data and summarized the experimental data; Yang Y did most of the experiments and wrote the first draft of the paper; Chen FL performed the statistical analysis of the data; all authors read, revised, and agreed to the final manuscript.
Institutional review board statement: The study was approved by the Ethics Committee of the Second People's Hospital of Chengdu.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author, upon reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article 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 NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wu Wen, Doctor, Chief Physician, Digestive Diseases, Chengdu Second People’s Hospital, No. 10 Qingyunan Street, Jinjiang District, Chengdu 610000, Sichuan Province, China. wenwu2@qq.com
Received: November 7, 2023
Peer-review started: November 7, 2023
First decision: December 31, 2023
Revised: January 16, 2024
Accepted: February 4, 2024
Article in press: February 4, 2024
Published online: March 15, 2024
Processing time: 125 Days and 20.6 Hours
Abstract
BACKGROUND

The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.

AIM

To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC.

METHODS

In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant.

RESULTS

The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002).

CONCLUSION

It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

Keywords: Pigment epithelium-derived factors; Vascular endothelial growth factor; Microvessel density; Colorectal adenoma; Colorectal cancer; Targeted therapy

Core Tip: Targeted therapy is one of the most widely recognized and accepted methods for the treatment of colorectal cancer (CRC). Recent years have brought an intense focus to the study of the angiogenic signaling pathway, there have been studies showing that the infiltration, staging, and metastasis of colorectal are related to pigment epithelium-derived factors (PEDF) and vascular endothelial growth factors, but the current domestic and foreign studies on PEDF almost do not involve colorectal adenoma, a precancerous lesion. In our study, colorectal adenoma, a precancerous lesion, was added to analyze and explore the possibility of PEDF as a new target for early prevention and later treatment of CRC.