VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

Mazeda, Inês; Martins, Sandra F.; García, Eduardo A. Pérez; Rodrigues, Mesquita; Longatto, Adhemar

doi:10.3390/gidisord2030025

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…As an essential angiogenic regulator, VEGF contributes to cancer genesis and development, but is also a vital therapeutic target ( 37 ). It has been suggested that up-regulation of VEGF is associated with advanced cancer stages, particularly lymph node metastasis and angiolymphatic invasion, and it may also predict a poor prognosis for CRC ( 38 , 39 ).Taken together, serum based miR-1539 may provide clues underpinning molecular mechanisms for discrepant CRC prognoses (RCRC versus LCRC), and targeted anti-VEGF therapy. However, further studies are required to verify these observations.…”

Section: Discussionmentioning

confidence: 99%

MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer

Cui

Ding

et al. 2021

Front. Oncol.

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PurposeWe investigated microRNA (miR) 1539 as a potential biomarker for predicting the risk and pathobiological behavior of colorectal cancer (CRC).MethodsOur strategy consisted of analyzing 100 serum samples from 51 CRC patients, 49 healthy controls (HCs), and another 56 CRC tissue and matched normal adjacent to tumor (NAT) samples. The relative expression levels of miR-1539 in exosomes, serum and tissues were detected and compared in the different groups, using reverse transcription-polymerase chain reaction (RT-qPCR). The diagnostic value and potential function of miR-1539 were investigated using clinicopathological data combined with bioinformatics analysis.ResultsMiR-1539 expression was significantly up-regulated in exosomes (p = 0.003) and cancer tissue (p < 0.001) from CRC patients. MiR-1539 expression levels in serum varied according to different tumor sites (right-sided vs. left-sided, p = 0.047; left-side CRC vs. HCs, p = 0.031). In terms of diagnostic efficacy, miR-1539 expression in exosomes may help distinguish CRC cases from HCs with a sensitivity of 92.2%, and miR-1539 expression in serum may improve the specificity to 96.6% for left-sided CRC diagnosis. When combined with clinicopathological data, serum miR-1539 levels were positively associated with vascular endothelial growth factor (VEGF) expression (p = 0.028), whilst levels in CRC tissue were positively associated with increased Ki-67 levels (p = 0.035). Poorer pathologic differentiation was potentially related to an increased tendency of miR-1539 expression in CRC tissue (p = 0.071). Based on our bioinformatics analysis, miR-1539 may have a significant mechanistic influence on CRC genesis and progression.ConclusionsCirculating or tissue based miR-1539 may be used as a novel potential biomarker for CRC screening, and a predictor of poor clinicopathological behavior in tumors.

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Section: Discussionmentioning

confidence: 99%

MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer

Cui

Ding

et al. 2021

Front. Oncol.

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“…In most papers, exposure to T3s caused downregulation of VEGFA in the CRC cells. Furthermore, in a clinical study involving lymph node metastasis (LNM) from patients with CRC, there was elevated expression of the VEGF family, especially of VEGFA in LNM, which was associated with the patients' age (p-value < 0.001) [55]. Interestingly, high expression of VEGFA in the primary tumor was positively associated with other ligands and receptors with regards to LNM, implying a mutual effect.…”

mentioning

confidence: 99%

“…Reduced RELA expression, resulting in deceased activation of the NF-κB signaling pathway, which inhibited carcinogenesis [52,53] Cancer progression CCND1 ()  CCND1 gene was detected in tumors from about 50% (54 out of 111) of CRC patients; absent in normal mucosa [54] VEGFA ()  Elevated expression of the VEGF family, especially of VEGFA, was reported in CRC patients with LNM [55] CTNNB1 ()  CTNNB1 codes for ꞵ-catenin, which supports tumor growth  A significant link between mutations in CTNNB1 gene and MSI [56]  Downregulat.ed;  Upregulated; CB: candidate biomarkers; CRC: colorectal carcinoma; LNM: lymph node metastasis; MSI: microsatellite instability; T3s: tocotrienols. Italics refer to the gene name of the protein.…”

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confidence: 99%

mentioning

confidence: 99%

“…Elevated expression of the VEGF family, especially of VEGFA, was reported in CRC patients with LNM [55] CTNNB1 ()…”

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confidence: 99%

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Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

et al. 2021

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The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.

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A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms

Zamanian,

Taheri,

Ramadan

et al. 2024

Anim Models and Exp Med

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Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria‐derived activator of caspase/direct inhibitor of apoptosis‐binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase‐2 and wingless‐related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin‐dependent kinase 2 and cyclin‐dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y‐box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal‐regulated kinase 1/2, and disrupting the repair process of DNA double‐strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit α (PIK3CA)‐mutant CRC, resulting in a reduction in phosphatidylinositol‐3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

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VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

Cited by 10 publications

References 26 publications

MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer

MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer

Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review

A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms

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