Expression of tumor suppressor programmed cell death 4 in endometrioid endometrial carcinomas and clinicopathological significance

Abstract

Programmed cell death 4 (PDCD4), as a novel tumor suppressor, serves important roles in the pathogenesis of tumors. The expression of PDCD4 is downregulated or lost in various human tumors. However, the expression of PDCD4 in endometrial cancer and the clinicopathological significance remain unclear. The aim of the present study was to investigate the expression of PDCD4 in endometrioid endometrial carcinoma (EEC) and the association with clinicopathological parameters. The expression of PDCD4 in EEC tissues and control endometrium was detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. PDCD4 expression was also investigated in control endometrial glandular epithelial cells and the endometrial cancer KLE cell line by immunocytochemistry, and the association between PDCD4 expression and clinicopathological parameters of patients with EEC was analyzed. The results demonstrated that PDCD4-positive staining was mainly located in the cytoplasm of endometrial glandular epithelial cells and EEC cells. The staining index of PDCD4 in the proliferative phase was significantly increased compared with that in the secretory phase of control endometrium (P<0.001). There was significantly decreased PDCD4 expression in grade (G) 2/3 EEC tissues compared with the proliferative phase of control endometrium (P<0.001). PDCD4 expression was significantly associated with tumor grade. The PDCD4 levels in G1 EEC tissues were higher compared with the G2/3 EEC group (P<0.01). The results indicated that PDCD4 is associated with the histological grade of EEC, and that PDCD4 may be a valuable indicator of the degree of tumor malignancy in patients with EEC.

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

“…PTEN, a tumor suppressor gene that negatively regulates PI3-AKT signaling pathway has been implicated in endometrial carcinogenesis (83), as has Notch, a regulator of cellular proliferation, differentiation and apoptosis (84). Angiogenesis has been shown to play an important role in the growth of EC (85) while PDCD4 expression has been linked to tumor grade in endometrioid EC (86). Srivastava and colleagues studied 81 microRNAs from urine derived exosomes from patients with and without EC, 57 of which were amplified in qPCR and reported has-miR-200c-3p to be differentially expressed (60).…”

TRIM27 regulates the expression of PDCD4 by the ubiquitin‑proteasome pathway in ovarian and endometrial cancer cells

“…Higher TRIM27 expression was significantly correlated with the metastasis and FIGO stage in patients with ovarian serous carcinoma, and an unfavorable clinical outcome in patients with endometrial cancer. PDCD4 was lowly expressed or deleted in ovarian serous cystadenocarcinomas and endometrioid endometrial carcinomas (EEC) (10,11). The loss or reduction of PDCD4 expression was significantly associated with higher pathological grade of ovarian serous cystadenocarcinomas and EEC, as well as the prognosis of patients with ovarian serous cystadenocarcinomas.…”

“…that PDCD4 overexpression could effectively suppress the migration and invasion, as well as the proliferation of cells in numerous types of cancer (6), such as breast (7), ovarian (8)(9)(10) and endometrial cancer (11). The expression level of PDCD4 is also related to the sensitivity of tumor cells to chemotherapeutic drugs.…”