Aberrant Expression TFR1/CD71 in Gastric Cancer Identifies a Novel Potential Prognostic Marker and Therapeutic Target.

Background: Gastric cancer (GC) is one of the most common malignant tumors with poor prognosis. So far, other than the HER2, GC lacks effective therapeutic targets. Transferrin receptor 1 (TFR1) expressions are abnormally upregulated in various cancers for the satisfaction of iron demand increased. This study aimed to explore the expression and clinical value of TFR1 in GC.

Methods: A tissue microarray including GC tissues and matched noncancerous tissues from 155 GC patients were collected. Moreover, the level of TFR1 expression was detected by immunohistochemistry, and we also evaluated the relationship between TFR1 expression and the clinicopathologic characteristics. What is more, univariate analysis and multivariate analysis were used to evaluate the risk factors and independent risk factors affecting the prognosis of GC.

Results: We found that TFR1 was overexpressed in GC tissues compared with noncancerous tissues, and a significant relationship was found between TFR1 expression and age (=0.001), Lauren type (=0.008), T stage (=0.003), HER2 (=0.003), PD-L1 ( < 0.001), and the level of CA72-4 (=0.028). Survival analysis confirmed that GC patients with positive TFR1 expression had a poorer OS than that with negative TFR1 expression, and TFR1 expression was an independent risk factor in GC. Furthermore, we also found that there was a significant difference between the TFR1-PD-L1- group and the TFR1+PD-L1+ group (=0.023), while there was no significant difference between the TFR1-PD-L1- group and the TFR1+PD-L1- group (=0.119), or between the TFR1-PD-L1- group and the TFR1-PD-L1+ group (=0.396).

Conclusions: TFR1 was overexpressed in GC and its aberrant expression identifies a novel potential prognostic marker and therapeutic target. In addition, TFR1 expression may be associated with the immune microenvironment and suppress the immune response via regulating the PD-L1 expression.