IKBIP is a Predictive Biomarker Related to Immunosuppressive Microenvironment in Digestive System Malignancies

Discov Med. 2023 Feb 1;35(174):57-72. doi: 10.24976/Discov.Med.202335174.7.

Abstract

Objective: IKBKB-interacting protein (IKBIP) has rarely been reported in tumor research. This study aimed to evaluate IKBIP role in tumor progression. mRNA (messenger ribonucleic acid) expression, clinical characteristics and predictive values of IKBIP were assessed.

Methods: R package "clusterProfiler" was used to examine the potential mechanisms in which IKBIP may involve. Immune cell infiltration and its correlation with IKBIP was also analyzed. We further evaluated IKBIP influence on drug resistance.

Results: It was found that IKBIP was overexpressed and related to poorer survival in most types of tumors. IKBIP expression was strongly related to immunosuppressive cells in the TCGA (The Cancer Genome Atlas) pan-cancer samples. These immunosuppressive cells included tumor-related macrophages, tumor-related fibroblasts, and regulatory T cells. Moreover, immunosuppressive genes and immune checkpoints were positively related to IKBIP expression in several tumor types. Furthermore, patients with IKBIP overexpressed did not respond to most anti-cancer medications. It was also found that compared to control group, the number of invasive cells is four times that of IKBIP overexpression group, and the number of clone forming cells is six times that of IKBIP overexpression group. IKBIP overexpression promoted colon cancer cells invasiveness and clonogenesis by Transwell assay and colon formation assay.

Conclusions: According to current findings, IKBIP is a probable oncogene and predictive marker for most of tumor types. High IKBIP expression is associated with tumor immunosuppression.

Keywords: IKBIP; TCGA; immunosuppressive microenvironment; macrophages; pan-cancer.

MeSH terms

  • Biomarkers
  • Colon
  • Digestive System Neoplasms*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Oncogenes
  • Tumor Microenvironment

Substances

  • Immunosuppressive Agents
  • Biomarkers