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

Abstract

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 ( P = 0.001 ), Lauren type ( P = 0.008 ), T stage ( P = 0.003 ), HER2 ( P = 0.003 ), PD-L1 ( P < 0.001 ), and the level of CA72-4 ( P = 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 ( P = 0.023 ), while there was no significant difference between the TFR1-PD-L1− group and the TFR1+PD-L1− group ( P = 0.119 ), or between the TFR1-PD-L1− group and the TFR1-PD-L1+ group ( P = 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.

Immunohistochemical evaluation of LGR5, CD71, CD138 and CXCR3 markers in the small bowel mucosa of participants with celiac disease and persons with normal bowel mucosa

“…There occurred signi cant correlation of CD71 with age for persons with normal small bowel mucosa. The literature has presented data about correlation between expression of this marker and age in the intestinal mucosa of gastric cancer, but not in the case of normal small bowel mucosa (Cao et al 2022). In the present study, number of CD71 + cells in normal small bowel mucosa showed strong negative correlation with IDO + tolerogenic DCs and density of EV in the small bowel mucosa, as found in our previous studies (Vorobjova et al 2015;.…”

Expression of monomorphic HLA-determinants, transferrin receptor 1 (TfR1) in molecular subtypes of breast cancer

“…Дополнительно, необходимо отметить, что некоторые экспериментальные и клинические исследования продемонстрировали выраженное противоопухолевое действие нацеленных на TfR1 антител [28,29]. Вероятно, TfR1 может рассматриваться как потенциальная молекулярная мишень не только для диагнос тики, но и для иммунотерапии рака, поскольку экспрессия TfR1 может быть связана с иммунным микроокружением и посредством регуляции экспрессии PD-L1 влиять на противоопухолевый иммунный ответ [30].…”