Beclin 1 expression is an independent prognostic factor for gastric carcinomas

Abstract

Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer progression, which is increased during periods of cell stress and extinguished during the cell cycle. In order to clarify the role of Beclin 1 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa, and metastatic lymph node. Gastric carcinoma tissue and cell lines were studied for Beclin 1 expression by Western blot or RT-PCR, respectively. The results demonstrated that Beclin 1 was distinctively expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, or STKM-2 at both mRNA and protein levels. However, Beclin 1 mRNA was highly expressed in gastric carcinoma than matched mucosa by real-time PCR and ISH (P < 0.05). Beclin 1 expression was negatively related to distant metastasis and poor prognosis of gastric carcinoma (P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric carcinoma (P < 0.05). The 65-year-elder patients with gastric carcinoma had higher Beclin 1 expression than the younger ones (P < 0.05). The diffuse-type carcinomas showed less Beclin 1 expression than intestinal- and mixed-type ones (P < 0.05). In intestinal-type gastric carcinoma, Beclin 1 expression was inversely associated with venous invasion, lymph node metastasis, and tumor-node-metastasis (TNM) staging (P < 0.05). Kaplan-Meier analysis indicated that Beclin 1 expression was positively linked to favorable prognosis of the patients with overall and intestinal-type carcinoma (P < 0.05). Cox's proportional hazard model indicated that venous invasion, lymph node metastasis, distant metastasis, TNM staging, and Beclin 1 expression were independent prognostic factors for gastric carcinomas (P < 0.05). It was suggested that aberrant Beclin 1 expression is closely linked to pathogenesis, metastasis, and differentiation of gastric carcinoma. Beclin 1 expression might be employed to indicate the favorable prognosis of gastric carcinomas as an independent factor.

Autophagy is related to the hedgehog signaling pathway in human gastric adenocarcinoma: Prognostic significance of Beclin-1 and Gli2 expression in human gastric adenocarcinoma

“…A study by Yu et al showed that increased Beclin-1 expression in gastric adenocarcinoma is correlated with favorable prognosis [15]. The results from our present study are consistent with their findings.…”

“…On the basis of these findings, Beclin-1 may be a haploinsufficient tumor suppressor gene. Yu et al reported that Beclin-1 expression is an independent prognostic factor of gastric carcinomas [15]. However, the biological functions of Beclin-1 in gastric adenocarcinoma need further investigation.…”

Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer

“…Besides, Beclin-1 has 3 domains which can interact with and constitute multiple regulatory pathways (Beclin-1-PI3KC3-Vpsl5 and Beclin-1-Bcl-2/Bcl-XL), and thereby regulates the development of tumors [14]. The expression level of Beclin-1 was found to be dysregulated and related to the clinical prognostic in divers types of cancer [15, 16]. Moreover, Beclin-1 was upregulated after cisplatin treatment, resulting in enhanced activity of autophagy and drug-resistance to treatment [17].…”

Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells

“…In addition, after chemotherapy or radiation therapy, autophagy activity in tumor cells becomes higher to remove large molecules or mitochondria damaged by ionizing radiation, block the mitochondrial apoptosis signaling cascade, and inhibit the apoptosis of tumor cells [5]. Autophagy plays an important role in the occurrence and progression of gastric cancer, especially during the development of resistance to chemotherapy [6,7].…”