AUTHOR=Talaat Iman M. , Yakout Nada M. , Soliman Ahmed S.A. , Venkatachalam Thenmozhi , Vinod Arya , Eldohaji Leen , Nair Vidhya , Hareedy Amal , Kandil Alaa , Abdel-Rahman Wael M. , Hamoudi Rifat , Saber-Ayad Maha 

TITLE=Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.877147

DOI=10.3389/fonc.2022.877147

ISSN=2234-943X

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, a neuropeptide ubiquitously present in the gut and other organs, in CRC progression. Eighty-one CRC cases (TNM stage 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 Mann-Whitney U test). Whole transcriptomic 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 tumour progression, 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 primary (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 CRC progression, and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response.