NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

Medicine (Baltimore). 2023 Oct 6;102(40):e35452. doi: 10.1097/MD.0000000000035452.

Abstract

Background: Immune-related initiation, progress, metastasis and sensitivity to treatment associated with poor prognosis of patients with colorectal cancer (CRC). The role of Nucleolar protein interacting with the FHA domain of MKI67 (NIFK) in CRC remained to be investigated. We explore whether NIFK correlates with tumor immune infiltration and plays an important role in CRC patient prognosis.

Methods: The data of samples involved in our study was obtained from TCGA and GEO and samples for protein expression detection and clinical information analysis were obtained from our hospital. NIFK expression, association with patient prognosis, correlation with infiltration of immune cells and its correlated genes involved in signaling pathways were analyzed using bioinformatics method along with experimental validation and clinical correlation analysis.

Results: Results indicated that the expression of NIFK in tumor tissues was significantly increased compared with normal samples. colon and rectal cancer patients with high NIFK expression have poor survival compared with those with low NIFK expression. Results of cell experiments indicated that NIFK is positively correlated with cell proliferation and migration in CRC. NIFK negatively correlated with T cell CD8+, Tregs, Neutrophil and macrophage significantly. DARS and NKRF were positively correlated with NIFK and DARS correlated with CD8 + T cell, CD4 + T cell, macrophage and Neutrophil, NKRF correlated with CD8 + T cell, CD4 + T cell and macrophage in colon and rectal cancer. NIFK along with its correlated genes as DARS and NKRF were involved in Wnt, PI3K-Akt, NF-κB signaling and Intestinal immune network for lgA production.

Conclusions: Our results suggested that NIFK might be a biomarker associated with poor prognosis of CRC patients, and it would be a potential target for CRC therapy.

MeSH terms

  • Colorectal Neoplasms* / pathology
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Rectal Neoplasms*
  • Signal Transduction

Substances

  • Phosphatidylinositol 3-Kinases
  • NIFK protein, human