Backgrounds
Early detection might help in reducing the burden and promoting the survival rate of gastric cancers. Herein, we tried to explore the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in gastric cancers.


Methods
In this study, we first analyzed the expression levels and prognostic value of IGFBP7 mRNA in gastric cancers from The Cancer Genome Atlas (TCGA) database. Then, we recruited 169 gastric cancer patients and 100 normal controls as training cohort, and 55 gastric cancer patients and 55 normal controls as independent validation cohort. Enzyme-linked immunosorbent assay was applied to test the serum levels of IGFBP7. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to evaluation the diagnostic value.


Results
TCGA showed that IGFBP7 mRNA was dysregulated and associated with prognosis in gastric cancer patients. Then, we examined the expression of serum IGFBP7 and found that serum IGFBP7 expressed lower in gastric cancer patients than normal controls both in training and independent validation cohorts (p < 0.0001). In training cohort, with the cutoff value of 1.515 ng/ml, the AUC for distinguishing gastric cancer patients was 0.774 (95% CI [0.713-0.836]) with sensitivity of 36.7% (95% CI [29.5-44.5]) and specificity of 90.0% (95% CI [82.0-94.8]). As for early-stage EJA, the AUC was 0.773 (95% CI [0.701-0.845]) with the sensitivity of 33.3% (95% CI [14.4-58.8]). In independent validation cohort, with the same cutoff value, the AUC reached to 0.758 (95% CI [0.664-0.852]). Similarly, for early-stage gastric cancer diagnosis in the independent validation cohort, the AUC value was 0.778 (95% CI [0.673-0.882]).


Conclusions
This study indicated that serum IGFBP7 might act as a potential early diagnostic marker for gastric cancers.

The diagnostic value of serum insulin-like growth factor binding protein 7 in gastric cancer

Research Progress of IGFBP7 in Digestive System Tumors

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer, and its development, growth, and invasiveness are regulated by the tumor microenvironment (TME). Insulin-like growth factor-binding protein-7 (IGFBP7), which is closely related to various tumors, transforming growth factor-β1 (TGFβ1), which is a key signal mediator in oncogenesis, α-smooth muscle actin (α-SMA), and collagen I are important components of the TME. IGFBP7 can upregulate the expression of TGFβ1 and activate the TGFβ1/SMAD signaling pathway, which leads to an increase in collagen I in hepatic stellate cells (HSCs). However, the contribution of IGFBP7 to TGFβ1 and the TME in the progression of ESCC remains unknown. In the present study, we investigated IGFBP7 expression and its effects on TGFβ1 and the TME in ESCC. A total of 45 patients were divided into three groups: early-tumor group (n=15), advanced-tumor group (n=15), and paracancer control group (n=15). The EC109 cell line was cultured and treated with AdIGFBP7 and LvshTGFβ1, and the expression levels of IGFBP7, TGFβ1, α-SMA, collagen I, and p-SMAD2/3 were determined by immunohistochemical staining and western blotting analysis. IGFBP7, TGFβ1, α-SMA, and collagen I were upregulated in the ESCC samples compared with the control samples (P<0.05), and the values peaked in the advanced-tumor group (P<0.05). Compared with the control group, the TGFβ1, α-SMA, p-SMAD2/3, and collagen I proteins were gradually increased from 24 to 72 h in the EC109 cells treated with AdIGFBP7 (P<0.05). Inhibition of TGFβ1 expression in the EC109 cells treated with AdIGFBP7 gradually reduced the expression of α-SMA, collagen I, and p-SMAD2/3 from 24 to 72 h (P<0.05). These findings suggest that increased IGFBP7 may accelerate the progression of ESCC by upregulating TGFβ1, α-SMA, and collagen I via activating the TGFβ1/SMAD signaling pathway, which could remodel the TME.

/pdf/igfbp7-remodels-the-tumor-microenvironment-of-esophageal-21cwaxkr.pdf

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

[This corrects the article DOI: 10.3892/ol.2022.13371.].

Ji Zhang

Papers

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway

IGFBP7 remodels the tumor microenvironment of esophageal squamous cell carcinoma by activating the TGFβ1/SMAD signaling pathway