Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 15;16(3):670-686.
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  1 , Wu Wen  2 , Feng-Lin Chen  3 , Ying-Jie Zhang  4 , Xiao-Cong Liu  4 , Xiao-Yan Yang  4 , Shan-Shan Hu  4 , Ye Jiang  4 , Jing Yuan  4
Affiliations

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer

Ye Yang et al. World J Gastrointest Oncol. .

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

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: The authors declare no competing interests.

Figures

Figure 1
Figure 1
General data of normal control group, adenoma group and colorectal cancer group. A: Three groups compared by gender; B: Three groups compared by age; C: Three groups compared by specimen origin. n = 50 (normal control group), n = 50 (adenoma group), n = 50 (colorectal cancer group). aP > 0.05.
Figure 2
Figure 2
Comparison of positive expression rate and expression intensity of pigment epithelium-derived factors and vascular endothelial growth factors in normal control group, adenoma group and colorectal cancer group. A: Positive expression rate of pigment epithelium-derived factors (PEDF) in the three groups; B: Expression intensity of PEDF in the three groups; C: Positive expression rate of vascular endothelial growth factors (VEGF) in the three groups; D: Expression intensity of VEGF in the three groups. n = 50 (normal control group), n = 50 (adenoma group), n = 50 (colorectal cancer group). PEDF: Pigment epithelium-derived factors; VEGF: Vascular endothelial growth factors.
Figure 3
Figure 3
Immunohistochemistry of pigment epithelium-derived factors (PEDF) in three groups. A: Pigment epithelium-derived factors (PEDF) immunohistochemistry (IHC) plot in normal group (IHC × 100); B: PEDF immunohistochemistry plot in normal group (IHC × 200). In the normal group, the nuclei of the study cells were brownish yellow, the number of positive cells was more than 75%, and the expression was strongly positive (+++); C: PEDF immunohistochemistry plot in adenoma group (IHC × 100); D: PEDF immunohistochemistry plot in adenoma group (IHC × 200). In the adenoma group, the nuclear color was mainly yellow, the number of positive cells was more than 75%, and the expression was moderately positive (++); E: PEDF immunohistochemistry plot in colorectal cancer (CRC) group (IHC × 100); F: PEDF immunohistochemistry plot in CRC group (IHC × 200). In the CRC group, the nucleus was almost uncolored, the number of positive cells was 0%, and the expression intensity was negative (-) expression. PEDF: Pigment epithelium-derived factors.
Figure 4
Figure 4
Immunohistochemistry of vascular endothelial growth factors in three groups. A: Vascular endothelial growth factors (VEGF) immunohistochemistry (IHC) plot in normal group (IHC × 100); B: VEGF immunohistochemistry plot in normal group (IHC × 200). In the normal group, the cytoplasm of the study cells was not colored and showed negative (-) expression; C: VEGF immunohistochemistry plot in adenoma group (IHC × 100); D: VEGF immunohistochemistry plot in adenoma group (IHC × 200). In the adenoma group, the cytoplasm was light yellow, the number of positive cells was more than 75%, and the expression was weak positive (+); E: VEGF immunohistochemistry plot in colorectal cancer (CRC) group (IHC × 100); F: VEGF immunohistochemistry plot in CRC group (IHC × 200). In the CRC group, the cytoplasm was expressed in yellow fine particles on the surface of the tumor cell cavity, and the number of positive cells was greater than 75%, showing moderately positive (++) expression. Note: In the normal group, adenoma group and CRC group, the expression of brown or yellow was widely seen in the colorectal stromal cells and vascular endothelial cells, which was used as a positive internal control. VEGF: Vascular endothelial growth factors.
Figure 5
Figure 5
The relationship between the expression of pigment epithelium-derived factors and vascular endothelial growth factors with clinical parameters in colorectal cancer group. A: The relationship between positive expression rate of pigment epithelium-derived factors (PEDF) and age, gender, tumor size, and tumor location in colorectal cancer (CRC) group; B: The relationship between high expression rate of vascular endothelial growth factors (VEGF) and age, gender, tumor size, and tumor location in CRC group; C: The relationship between positive expression rate of PEDF and tumor differentiation, serous membrane infiltration, lymph node metastasis, remote metastasis and staging tumors in CRC group; D: The relationship between high expression rate of VEGF and tumor differentiation, serous membrane infiltration, lymph node metastasis, remote metastasis and staging tumors in CRC group. High expression: +++; Low expression: -~++; n = 50 (CRC group), NS: P ≥ 0.05. PEDF: Pigment epithelium-derived factors; VEGF: Vascular endothelial growth factors.
Figure 6
Figure 6
CD31-stained microvessel density values and correlation analysis. A: Difference of CD31-stained microvessel density values (CD31-MVD) value in normal group, adenoma group, and colorectal cancer (CRC) group; B: Correlation between pigment epithelium-derived factors (PEDF) and CD31-MVD value in adenoma group; C: Correlation between vascular endothelial growth factors (VEGF) and CD31-MVD value in adenoma group; D: Correlation between PEDF and VEGF in CRC group; E: CRC group Association between PEDF and CD31-MVD value in CRC; F: Association between VEGF and CD31-MVD value in CRC. CD31-MVD: CD31-stained microvessel density values; PEDF: Pigment epithelium-derived factors; VEGF: Vascular endothelial growth factors.
Figure 7
Figure 7
Immunohistochemistry of CD31 in three groups. A: CD31 immunohistochemistry plot in normal group (IHC × 100); B: CD31 immunohistochemistry plot in normal group (IHC × 200). In the normal group, no obvious stained vascular endothelial cells or endothelial cell clusters were found; C: CD31 immunohistochemistry plot in adenoma group (IHC × 100); D: CD31 immunohistochemistry plot in adenoma group (IHC × 200). In the adenoma group, a few vascular endothelial cells were found to be colored brown; E: CD31 immunohistochemistry plot in colorectal cancer (CRC) group (IHC × 100); F: CD31 immunohistochemistry plot in CRC group (IHC × 200). In CRC group, a large number of brown vascular endothelial cells were observed. IHC: Immunohistochemistry.
Figure 8
Figure 8
receiver operating characteristic curve of pigment epithelium-derived factors and vascular endothelial growth factors in the diagnosis of colorectal cancer. AUC: Area under the curve; PEDF: Pigment epithelium-derived factors; VEGF: Vascular endothelial growth factors.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–249. - PubMed
    1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191–197. - PMC - PubMed
    1. Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, Vignat J, Ferlay J, Murphy N, Bray F. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72:338–344. - PubMed
    1. Leslie A, Carey FA, Pratt NR, Steele RJ. The colorectal adenoma-carcinoma sequence. Br J Surg. 2002;89:845–860. - PubMed
    1. Lepore Signorile M, Grossi V, Fasano C, Simone C. Colorectal Cancer Chemoprevention: A Dream Coming True? Int J Mol Sci. 2023;24 - PMC - PubMed