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

Frontiers in Oncology

Maha Saber-Ayad¹  Alaa Kandil²  Wael M. Abdel-Rahman⁴  Thenmozhi Venkatachalam⁵  Rifat Hamoudi⁶  Nada M. Yakout⁷  Iman M. Talaat⁷  Amal Hareedy⁸  Ahmed S.A. Soliman⁹  Leen Eldohaji^1,10  Vidhya Nair^1,10  Arya Vinod^1,10 

[1] 0Pharmacology Department, Faculty of Medicine, Cairo University, Cairo, Egypt;Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Alexandria University, Cairo, Egypt;Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates;Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates;Department of Physiology and Immunology, College of Medicine and Health Science, Khalifa University, Abu Dhabi, United Arab Emirates;Division of Surgery and Interventional Science, University College London, London, United Kingdom;Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt;Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt;Pathology Department, National Research Center, Cairo, Egypt;Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates;

关键词: galanin;    immunohistochemistry;    transcriptomic analysis;    GALR1;    colorectal cancer;    bioinformatics;   

DOI  :  10.3389/fonc.2022.877147

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown