Beclin‑1 expression is associated with prognosis in a Bcl‑2‑dependent manner in non‑small cell lung cancer

Abstract

Beclin-1 and Bcl-2 expression abnormalities have been confirmed in different types of cancer. As important regulators of autophagy and apoptosis, respectively, these molecules serve a complex role in tumorigenesis. However, limited information is currently available regarding the association between Beclin-1 and Bcl-2 in (NSCLC). In the present study, the expression levels of Beclin-1 and Bcl-2 were detected in lung cancer tissues, and their prognostic significance was analyzed for NSCLC. A total of 120 patients with lung cancer who underwent surgical resection were included in the present study. Beclin-1 and Bcl-2 expression was assessed using immunohistochemistry and their associations with the overall survival (OS) in patients with NSCLC was examined. The expression rate of Beclin-1 was significantly lower in NSCLC tissues compared with that in adjacent tissues, whereas the expression rate of Bcl-2 was significantly higher in lung cancer tissues compared with that in adjacent tissues. Additionally, Beclin-1 and Bcl-2 protein expression was strongly associated (P<0.05) in NSCLC. Patients with NSCLC with low Beclin-1 expression were in more advanced stages, with more lymph node metastasis and more poorly differentiated tumors. Similarly, patients with NSCLC with high Bcl-2 expression were also in a more advanced stage and had more lymph node metastasis. Cox regression analysis revealed that the association between Bcl-2 expression and survival was not significant, while a multivariate analysis revealed that Beclin-1 expression was significantly associated with OS. Notably, Beclin-1 expression was significantly associated with OS only in patients with high Bcl-2 expression. In conclusion, the present data indicated that the autophagy activity is decreased in NSCLC. Beclin-1 expression was downregulated, while Bcl-2 expression was upregulated in NSCLC tissues compared with that in adjacent tissues. Additionally, these two proteins were associated with the occurrence and progression of NSCLC. Beclin-1 may be a promising prognostic marker for patients with NSCLC with high Bcl-2 expression. The present findings provided a more accurate prognostic assessment for patients with NSCLC. Furthermore, they may be used to actively follow-up and promptly treat patients with a poor prognosis, which may benefit a greater number of patients with NSCLC.

Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2‑STAT1‑Mcl‑1 axis

“…It was demonstrated that ruxolitinib partly suppressed CRC cell proliferation by inducing apoptosis through activating the intrinsic pathway. Bcl-2 family proteins that are key mediators of the intrinsic apoptosis pathway were screened out ( 25 , 26 ). As shown in Fig.…”

“…Briefly, 2,000 cells/well were plated in 96-well plates and incubated for 24 h and then exposed to gradually increasing concentrations (0, 2. 5,5,10,15,20,25,30,40, 50 µM) of ruxolitinib for 48 h. MTT solution (prepared in serum-free growth medium) was added to each well and was incubated for another 4 h at 37˚C. DMSO was added and the absorbance at 570 nm was determined using a microplate reader.…”

Establishment and validation of individualized clinical prognostic markers for LUAD patients based on autophagy-related genes

“…Furthermore, a systematic review and meta-study of p62/SQSTM1 in lung cancer patients found that overexpression of p62 was linked to overall survival in lung cancer patients [37,38]. Beclin-1 expression was negatively correlated with tumor size and tumor stage of lung adenocarcinoma, and Beclin-1 expression was decreased in NSCLC tissues compared with normal tissues [39].…”

Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review)

“…Autophagy is involved in cancer cell metastasis by regulating EMT. The autophagy protein Beclin1 is a key regulator of tumorigenesis and metastasis in NSCLC cells, and the expression levels of Beclin1 have been shown to be significantly reduced in NSCLC tissues ( 69 , 70 ). Low Beclin1 expression levels have also been observed in patients with NSCLC with more advanced stages of cancer, increased lymph node metastasis and more poorly differentiated tumors ( 70 ).…”

“…The autophagy protein Beclin1 is a key regulator of tumorigenesis and metastasis in NSCLC cells, and the expression levels of Beclin1 have been shown to be significantly reduced in NSCLC tissues ( 69 , 70 ). Low Beclin1 expression levels have also been observed in patients with NSCLC with more advanced stages of cancer, increased lymph node metastasis and more poorly differentiated tumors ( 70 ). Reduced Beclin1 expression has also been associated with shorter survival of patients with NSCLC, thus suggesting that autophagy, which is an independent prognostic indicator for the survival of patients with NSCLC, may be suppressed in these patients ( 69 ).…”