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<p>The alpha kinase family, encompassing <i>ALPK1</i>, <i>ALPK2</i>, and <i>ALPK3</i>, has been associated with a variety of biological processes, including DNA repair and cell division. Nevertheless, the alterations in the expression of these genes and their correlations with the development and progression of colorectal cancer (CRC) remain relatively understudied. In this study, the potential of the alpha kinase family, including changes in expression and associated pathways, in CRC development and malignancy was the primary focus. The differential expression of <i>ALPK1</i>,<i> ALPK2</i>, and <i>ALPK3</i> in CRC and their correlation with clinical characteristics and patient survival were examined using TCGA data. The protein expression levels associated with them were examined in CRC samples. To investigate the relationship between candidate gene expression and immune infiltration characteristics, the TIMER2.0 database was used. Co-expression network analysis was employed to explore potential pathways associated with the candidate genes. Fifty CRC samples, along with 50 adjacent normal tissue samples, were used for further validation by RT-qPCR. A significant increase in mRNA and protein levels of <i>ALPK2</i> and <i>ALPK3</i> was observed in CRC samples. <i>ALPK3</i> expression was associated with clinical features, including stage IV and TNM N2, and with poorer patient prognosis. Additionally, the results indicated that <i>ALPK2</i> and <i>ALPK3</i> expression levels were specifically associated with immune infiltration, particularly by cancer-associated fibroblasts and neutrophils. Co-expression network analysis also revealed strong correlations between <i>ALPK2</i> and <i>ALPK3</i> and genes associated with the main metastatic pathway (Epithelial-Mesenchymal Transition). RT-qPCR results showed that <i>ALPK2</i> and <i>ALPK3</i> expression levels were significantly higher in CRC samples than in adjacent normal tissue. <i>ALPK2</i> and <i>ALPK3</i> are overexpressed in CRC and may be associated with metastatic pathways and immune infiltration. These findings suggest that ALPK2 and ALPK3 may have potential relevance as diagnostic and therapeutic targets in CRC; however, further experimental and clinical validation is required.</p>

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Overexpression of ALPK2 and ALPK3 is Associated with Metastatic Pathways and Immune Infiltration in Colorectal Cancer

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Elahe Attari,
  • Arshida Mokhtarpour,
  • Mohammad Eslamipour,
  • Mehrzad Nikanjam,
  • Ensieh Sagheb Sadeghi,
  • Atefeh Zamani,
  • Mohammad Mahdevar

摘要

The alpha kinase family, encompassing ALPK1, ALPK2, and ALPK3, has been associated with a variety of biological processes, including DNA repair and cell division. Nevertheless, the alterations in the expression of these genes and their correlations with the development and progression of colorectal cancer (CRC) remain relatively understudied. In this study, the potential of the alpha kinase family, including changes in expression and associated pathways, in CRC development and malignancy was the primary focus. The differential expression of ALPK1, ALPK2, and ALPK3 in CRC and their correlation with clinical characteristics and patient survival were examined using TCGA data. The protein expression levels associated with them were examined in CRC samples. To investigate the relationship between candidate gene expression and immune infiltration characteristics, the TIMER2.0 database was used. Co-expression network analysis was employed to explore potential pathways associated with the candidate genes. Fifty CRC samples, along with 50 adjacent normal tissue samples, were used for further validation by RT-qPCR. A significant increase in mRNA and protein levels of ALPK2 and ALPK3 was observed in CRC samples. ALPK3 expression was associated with clinical features, including stage IV and TNM N2, and with poorer patient prognosis. Additionally, the results indicated that ALPK2 and ALPK3 expression levels were specifically associated with immune infiltration, particularly by cancer-associated fibroblasts and neutrophils. Co-expression network analysis also revealed strong correlations between ALPK2 and ALPK3 and genes associated with the main metastatic pathway (Epithelial-Mesenchymal Transition). RT-qPCR results showed that ALPK2 and ALPK3 expression levels were significantly higher in CRC samples than in adjacent normal tissue. ALPK2 and ALPK3 are overexpressed in CRC and may be associated with metastatic pathways and immune infiltration. These findings suggest that ALPK2 and ALPK3 may have potential relevance as diagnostic and therapeutic targets in CRC; however, further experimental and clinical validation is required.