Heliyon (Sep 2024)
Integrated bioinformatics analysis and validation identify KIR2DL4 as a novel biomarker for predicting chemotherapy resistance and prognosis in colorectal cancer
Abstract
Background: Chemotherapy and immunotherapy have improved the cure rate and survival period for colorectal cancer (CRC), but genetic heterogeneity among patients leads to chemotherapy resistance and disease progression. Identifying new molecular markers is crucial for improving prognosis for CRC patients. KIR2DL4, a transmembrane glycoprotein expressed by immune cells, has shown potential therapeutic and prognostic value in other cancers, but in CRC remains unclear. Methods: This study validated the expression levels of KIR2DL4 in CRC by integrating multiple public databases and assessed through immunohistochemistry (IHC). We further evaluated the diagnostic and prognostic value of KIR2DL4 and explored correlation with immune cell infiltration and chemotherapy sensitivity. The role of KIR2DL4 was further validated through functional enrichment analysis. Cellular assays were conducted using CCK8, colony-formation assay and scratch wound assay. Results: The study found that KIR2DL4 is significantly downregulated in CRC and closely associated with poor prognosis. The low expression of KIR2DL4 is associated with decreased immune cell infiltration and reduced chemotherapy sensitivity. Functional enrichment analysis suggests that KIR2DL4 may inhibit development of CRC by affecting immune cell infiltration and modulating chemotherapy sensitivity. Cellular assays have confirmed that inhibiting KIR2DL4 significantly promotes the proliferation and migration of CRC. Inhibition of KIR2DL4 expression significantly decreased the chemosensitivity of CRC cells to oxaliplatin and 5-FU. Conclusion: The significant downregulation of KIR2DL4 in CRC, associated with CRC metastasis and poor prognosis, highlights its importance as a potential new biomarker for treatment and prognosis assessment of CRC. Future research should delve into the molecular mechanisms of KIR2DL4 and potential applications in regulating immunotherapy and chemotherapy sensitivity.
