Progastrin: a potential predictive marker of liver metastasis in colorectal cancer

Westwood, David A.; Patel, Oneel; Christophi, Christopher; Shulkes, Arthur; Baldwin, Graham S.

doi:10.1007/s00384-017-2822-8

Cited by 8 publications

(9 citation statements)

References 11 publications

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“…GRP, gastrin-releasing peptide, mainly regulates numerous functions of the gastrointestinal and central nervous systems and plays an important role in human various cancers. GRP expression may be a predictive of aggressive tumor biomarkers for stratifying stages of colorectal cancer [26]. Downregulation of the GRP reduced the numbers of cancer stem cells in vitro and further abolished tumor development in SCID mice [27].…”

Section: Discussionmentioning

confidence: 99%

Hub Genes and Key Pathway Identification in Colorectal Cancer Based on Bioinformatic Analysis

2019

BioMed Research International

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Colorectal cancer (CRC) is one of the most common malignant tumors. The aim of the present study was to identify key genes and pathways to improve the understanding of the mechanism of CRC. GSE87211, including 203 CRC samples and 160 control samples, was screened to identify differentially expressed genes (DEGs). In total, 853 DEGs were obtained, including 363 upregulated genes and 490 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed to obtain enrichment datasets. GO analysis showed that DEGs were significantly enriched in the extracellular region, cell-cell signaling, hormone activity, and cytokine activity. KEGG pathway analysis revealed that the DEGs were mainly enriched in the cytokine-cytokine receptor interaction, drug metabolism, androgen and estrogen metabolism, and neuroactive ligand-receptor interaction. The Protein-Protein Interaction (PPI) network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes (STRING). The app MCODE plugged in Cytoscape was used to explore the key modules involved in disease development. 43 key genes involved in the top two modules were identified. Six hub genes (CXCL2, CXCL3, PTGDR2, GRP, CXCL11, and AGTR1) were statistically associated with patient overall survival or disease-free survival. The functions of six hub genes were mainly related to the hormone and chemokine activities. In conclusion, the present study may help understand the molecular mechanisms of CRC development.

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Section: Discussionmentioning

confidence: 99%

Hub Genes and Key Pathway Identification in Colorectal Cancer Based on Bioinformatic Analysis

2019

BioMed Research International

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“…From the studied group of NPs/NP-Rs, some were overexpressed in pCRC tissues compared with control, which might be linked to liver metastases. These molecules include (alphabetically): AT1R [198], BDNF [183], ET-1 [117], galanin [120], gastrin [210], NK-1R and SP [218], progastrin [47], TrKB [181], TrKC [182] and co-expression of BDNF/TrKB [183]. Lack of or significantly lower tumor expression versus control, which might also play a role in LM, was demonstrated for several NP/NP-Rs system components: CRHR2 [96], GRP/GRPR [142,146], SM [221], Sst2 [222], as well as Sst2 and Sst5 [223].…”

Section: Tissue Expression Of Np System Components In Crc and Liver Metastasismentioning

confidence: 99%

“…Discovery of several NPs in the large intestine, as well as the elucidation of their roles, has a significant clinical application. Some of them (e.g., progastrin) were even considered as potential tissue CRC LM biomarkers [47]. Others (e.g., Glucagon-like Peptide (GLP) and peptide YY (PYY)) are used in immunophenotypic classification and prognosis of rectal NETs.…”

Section: Introductionmentioning

confidence: 99%

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Kasprzak

Adamek

2020

IJMS

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Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

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“…David et al. found progastrin as a potential predictive marker of liver metastasis in CRC by immunohistochemistry ( 10 ); other researchers identified HOXD10, SLC13A2, OSM, MMP3, CXCL6, and CXCL8 as liver metastasis-associated hub genes of CRC through bioinformatics ( 11 ). Zhang et al.…”

Section: Introductionmentioning

confidence: 99%

“…Cytokines and chemokines are believed to be secreted by the primary tumor and fertilize distal origin through blood circulation, facilitating metastasis (8,9). David et al found progastrin as a potential predictive marker of liver metastasis in CRC by immunohistochemistry (10); other researchers identified HOXD10, SLC13A2, OSM, MMP3, CXCL6, and CXCL8 as liver metastasis-associated hub genes of CRC through bioinformatics (11). Zhang et al suggested that AMBP, F2, APOH, and other seven hub genes might be related to metastasis (12).…”

Section: Introductionmentioning

confidence: 99%

Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis

Liu

Zhang

et al. 2021

Front. Oncol.

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Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.

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Progastrin: a potential predictive marker of liver metastasis in colorectal cancer

Abstract: This is the first study to show that progastrin expression may be predictive of aggressive tumour behaviour in patients with colorectal cancer and supports its clinical relevance and potential use as a biomarker.

Cited by 8 publications

References 11 publications

Hub Genes and Key Pathway Identification in Colorectal Cancer Based on Bioinformatic Analysis

Hub Genes and Key Pathway Identification in Colorectal Cancer Based on Bioinformatic Analysis

The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis

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