Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

Abstract

PurposeWe aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.MethodsBeclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous cell carcinoma (SCC), 40 samples of high-grade cervical intraepithelial neoplasia (CIN), and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ2 and Fisher’s exact tests. Differences in overall survival (OS) were determined using the Kaplan–Meier method and log-rank tests.ResultsCervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000). Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000). No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of Gynecology and Obstetrics (FIGO) stage (P=0.011 and P=0.013, respectively) and pelvic lymph node metastasis (P=0.036 and P=0.092, respectively). The 5-year OS rates did not significantly differ between Beclin1- or LC3-positive and -negative patients with positive EGFR.ConclusionAutophagy was downregulated and EGFR was upregulated in cervical SCC. Autophagy downregulation combined with EGFR upregulation promotes the progression of cervical SCC.

Beclin1 overexpression suppresses tumor cell proliferation and survival via an autophagy‑dependent pathway in human synovial sarcoma cells

“…The antitumor effect of Beclin1 has been confirmed in many types of tumors such as breast ( 10 , 11 ), colon ( 12 , 13 ), cervical ( 14 , 15 ) ovarian cancer ( 16 , 17 ) and glioblastoma ( 18 , 19 ). Some studies have reported that the expression level of Beclin1 is significantly lower in ovarian cancer tissue than in normal ovarian tissue ( 20 , 21 ); moreover, inhibited proliferation was observed in breast cancer cells with high expression level of Beclin1 ( 22 , 23 ).…”

Tension induces intervertebral disc degeneration via endoplasmic reticulum stress-mediated autophagy

“…LC3-II–PE extends the membrane of autolysosome to form autolysosome [35,36]. Studies have shown that endoplasmic reticulum stress can induce autophagy [37] and the activation of autophagy is achieved through the activation of death associated proteins that phosphorylate Beclin-l [38]. We find that autophagy-related proteins Beclin1 and LC3 were significantly increased in the model, indicating that intervertebral disc degeneration may lead to autophagy and Beclin1 and LC3 may be involved in the occurrence of autophagy as a result of endoplasmic reticulum stress.…”

Facing Cell Autophagy in Gastric Cancer – What Do We Know so Far?

“…Beclin-1, a yeast ATG6 homolog, is the first step in autophagosome formation and one of the important initiators of autophagy, and the expression level of Beclin-1 tends to rise during autophagy. 13 Beclin-1 is necessary to initiate the process of autophagy, decreased levels of autophagy in GC can be revealed by decreased expression of Beclin-1. 14 In addition, Beclin-1 plays a key role in promoting autophagy-induced apoptosis resistance, and there is a positive correlation between the expression of Beclin-1, Bcl-2 and Bcl-xl, Beclin-1 can also induce the Bcl-2 and Bcl-xl expression, alternatively, down-regulate the protein levels of Bak and Bax, Cyto-C, Apaf-1, Smac, Caspase and cleaved Caspase, and thus inhibiting the apoptosis of GC cells but inducing autophagy in GC cells.…”