The recent research found that IGF regulator genes played a pivotal role in multiple biological processes, which may be developed for cancer treatment. However, the characteristics and implication of IGF regulators in cancers, especially in clear cell renal cell carcinoma (ccRCC), remain elusive.
We systematically analyzed the expression, prognostic valuation, genome variation, and functional implication at pan-cancer level from The Cancer Genome Atlas. According to expression levels of IGF regulator genes, ccRCC could be divided into three different subtypes
We found that IGF regulator genes were specifically upregulated in various cancer tissues, which were correlated with copy number variations and dysregulated pathways. IPCS1, IPCS2, and IPCS3 exhibited different clinical profiles and biological characteristics in ccRCC. IPCS3 subtype indicated a higher clinical stage and a worse survival. IPSC3 ccRCC displayed activated metabolic signatures to fuel the cancer progression. IPCS3 subgroup holds a higher tumor mutation burden and lower immune activities, which resulted in a low ICI therapy response and tumor immunity dysfunction state. The genome copy numbers of IPCS2/3, including arm gain and arm loss, were significantly higher than IPCS1. Besides, the drug sensitivity profiles were different among the three subgroups. The prognostic risk model based on subtype’s biomarker exerted a promising performance both in training and validation cohorts. Finally, upregulated expression of SHC1 partly induced poorer immunotherapy response and shorter survival of ccRCC patients.
Targeting IGF regulators may be functioned as a treatment approach among multi-cancers. IGF regulator–related signature could reshape the tumor immune microenvironment