همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Comprehensive Analysis of DCLK Family Kinases in Gastrointestinal Cancers and Neoplastic Progression

نویسندگان :

Zahra Salehi¹ Leili Rejali² Moein Piroozkhah³ Pooya Jalali⁴ Ali Aghajani⁵ Mahsa Saeedi Niyasar⁶ Binazir Khanabadi⁷ Amir Sadeghi⁸ Ehsan Nazemalhossein Mojarad⁹

1- Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. 2- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 5- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran 6- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 7- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 9- Department of Surgery, Leiden University Medical Center, RC Leiden, The Netherlands.

کلمات کلیدی :

DCLK family kinases،Gastrointestinal cancers،Neoplasia،Bioinformatics،Biomarkers

چکیده :

The doublecortin-like kinase (DCLK) family genes encode protein kinases that are critical for cell development, signaling pathways, and tumor progression across various cancers. Understanding the diagnostic and prognostic relevance of DCLK family genes in gastric cancers (GCs) is therefore essential. This study utilized data from The Cancer Genome Atlas (TCGA) and public databases such as GEPIA2, UALCAN, OncoDB, and cBioPortal to analyze the expression, methylation, and genetic alterations of DCLK family genes, along with their association with overall survival (OS). Gene regulatory networks, including transcription factors and competing endogenous RNAs, were explored using tools like htfTarget, mirTarbase, circBank, and TISIDB, while correlations with immune cell infiltration were also assessed. Additionally, DCLK gene expression was validated via quantitative real-time PCR (qRT-PCR) in 120 colon lesions (60 precancerous samples with adjacent normal tissues and 60 cancerous/non-cancerous samples) and 30 pancreatic ductal adenocarcinoma (PDAC) lesions with 30 corresponding non-cancerous tissues from surgical patients. ROC curve analyses were performed to assess the biomarker potential of DCLK genes. Our findings indicate that DCLK genes exhibit frequent mutations across multiple gastric cancer subtypes. Aberrant DCLK gene expression was notably linked to the progression of colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and pancreatic adenocarcinoma (PAAD). Elevated DCLK1 expression correlated with poorer prognosis in stomach adenocarcinoma (STAD), while reduced expression was associated with worse outcomes in cholangiocarcinoma (CHOL). Similarly, DCLK2 upregulation predicted poor prognosis in STAD, whereas downregulation correlated with unfavorable OS in PAAD. Importantly, DCLK genes influenced the tumor immune microenvironment, with DCLK1 and DCLK2 linked to immune cell infiltration, including CD8, CD4, Th1, NK cells, and macrophages in GCs. Experimental results further confirmed significant upregulation of DCLK1 and DCLK3 in precancerous and cancerous colon lesions compared to normal tissues. In PDAC samples, DCLK2 showed notable upregulation compared to non-cancerous tissues. ROC analyses highlighted the DCLK family's potential as prognostic biomarkers, particularly in PDAC.These results underscore the significant prognostic value of DCLK family genes, highlighting their potential as biomarkers for improving patient outcomes through individualized and targeted treatment approaches.