Pan‐cancer analysis of oncogenic role of insulin‐like growth factor‐binding proteins and validation in ovarian cancer

Abstract

Background Numerous studies have shown that the insulin‐like growth factor (IGF) pathway is highly associated with tumor initial and progression in several tumors. However, compared with IGF1/1R and IGF2/2R, insufficient studies have focused on IGF‐binding proteins (IGFBPs). Methods The GDC TCGA and GTEx data of 33 cancers, TCGA pan‐cancer immune phenotypes, tumor mutation burdens, and the copy number alterations of IGFBPs were extracted. Next, the prognostic value of IGFBPs was analyzed based on a univariate Cox analysis. Additionally, the ESTIMATE algorithm was used to calculate stromal and immune scores and tumor purity, and the CIBERSORT algorithm was used to estimate tumor‐infiltrating immunocyte levels. Ultimately, the correlation between IGFBP expression and cancer hallmark pathways was estimated with a Spearman analysis. Results The expression of IGFBPs was differentially expressed and correlated with prognosis in specific cancers. IGFBPs may operate as biological markers for carcinogenesis and progression and as prognostic biomarkers. Additionally, IGFBP5 has been proved that promotes the invasion and migration of ovarian cancer. Conclusions In general, IGFBPs can serve as predictable biomarkers and potential therapeutic targets for specific tumors. Our results could provide underlying targets for the design of laboratory experiments to elucidate the mechanism of IGFBPs in cancers and identify IGFBP5 as a prognostic factor in ovarian cancers.

Role of increased IGFBP2 in trophoblast cell proliferation and recurrent spontaneous abortion development: A pilot study

“…IGFBP2, a crucial member of the IGFBP family and a 36‐kDa protein that is highly produced throughout fetal development, has been recognized as a significant oncogene (Shimasaki & Ling, 1991 ; Wei et al., 2021 ). IGFBP2 and the functionality of cancer cells are intimately connected, according to numerous studies (Prayudi et al., 2020 ; Sun et al., 2021 ; Tan et al., 2023 ; Tang et al., 2018 ; Zheng et al., 2020 ; Zhu et al., 2019 ). The heparin‐binding domain 1 of matured IGFBP2 is required for IGFBP2‐mediated cell proliferation, migration, and invasion (Arai et al., 1996 ; Li et al., 2020 ; Russo et al., 1997 , 1999 , 2005 ).…”

“…In all of these species, IGFs and a number of small‐molecular‐weight IGFBPs, particularly IGFBP‐2 and IGFBP‐4, are thought to stimulate or inhibit follicular development and maturation (Mazerbourg & Monget, 2018 ). In ovarian cancer, IGFBPs can serve as predictable biomarkers and potential therapeutic targets (Prayudi et al., 2020 ; Tan et al., 2023 ; Zheng et al., 2020 ). IGFBP‐2 is primarily expressed in fetal tissues that are highly proliferative (Li et al., 2020 ) including the early postimplantation progenitor cells of the upper layer, the ventricular region of the rostral neuroepithelium (Pintar et al., 1991 ; Wood et al., 1992 ), the apical ectodermal crest (van Kleffens et al., 1998 ), and progenitor cells of the spleen (Pintar et al., 1991 ) and liver (Streck & Pintar, 1992 ).…”