Talaat, IM;
Yakout, NM;
Soliman, ASA;
Venkatachalam, T;
Vinod, A;
Eldohaji, L;
Nair, V;
... Saber-Ayad, M; + view all
(2022)
Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study.
Frontiers in Oncology
, 12
, Article 877147. 10.3389/fonc.2022.877147.
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Abstract
Colorectal cancer (CRC) represents around 10% of all cancers, with an increasing incidence in the younger age group. The gut is considered a unique organ with its distinctive neuronal supply. The neuropeptide, human galanin, is widely distributed in the colon and expressed in many cancers, including the CRC. The current study aimed to explore the role of galanin at different stages of CRC. Eighty-one CRC cases (TNM stages I – IV) were recruited, and formalin-fixed paraffin-embedded samples were analyzed for the expression of galanin and galanin receptor 1 (GALR1) by immunohistochemistry (IHC). Galanin intensity was significantly lower in stage IV (n= 6) in comparison to other stages (p= 0.037 using the Mann-Whitney U test). Whole transcriptomics analysis using NGS was performed for selected samples based on the galanin expression by IHC [early (n=5) with high galanin expression and late (n=6) with low galanin expression]. Five differentially regulated pathways (using Absolute GSEA) were identified as drivers for tumor progression and associated with higher galanin expression, namely, cell cycle, cell division, autophagy, transcriptional regulation of TP53, and immune system process. The top shared genes among the upregulated pathways are AURKA, BIRC5, CCNA1, CCNA2, CDC25C, CDK2, CDK6, EREG, LIG3, PIN1, TGFB1, TPX2. The results were validated using real-time PCR carried out on four cell lines [two primaries (HCT116 and HT29) and two metastatic (LoVo and SK-Co-1)]. The current study shows galanin as a potential negative biomarker. Galanin downregulation is correlated with advanced CRC staging and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response.
| Type: | Article |
|---|---|
| Title: | Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fonc.2022.877147 |
| Publisher version: | https://doi.org/10.3389/fonc.2022.877147 |
| Language: | English |
| Additional information: | © 2022 Talaat, Yakout, Soliman, Venkatachalam, Vinod, Eldohaji, Nair, Hareedy, Kandil, Abdel-Rahman, Hamoudi and Saber-Ayad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | galanin, immunohistochemistry, transcriptomic analysis, GALR1, colorectal cancer, bioinformatics, TIMER 2 |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10154296 |
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