Decreased expression of speckle-type POZ protein for the prediction of poor prognosis in patients with non-small cell lung cancer

Abstract

Speckle-type POZ domain protein (SPOP) has been acknowledged as a tumor suppressor gene in numerous types of cancer. However, SPOP expression and its prognostic role in human non-small cell lung cancer (NSCLC) remain unknown. The present study investigated SPOP expression in NSCLC and evaluated its prognostic significance in patients with NSCLC. The results demonstrated that SPOP expression was significantly downregulated in NSCLC tissues at the mRNA and protein level compared with normal lung tissues using reverse transcription-quantitative polymerase chain reaction, and western blot analysis. Immunohistochemical staining results also demonstrated that SPOP was expressed at a low level in 84.1% (132/157) of NSCLC samples and at a high level in 52.2% (12/23) of normal lung samples, whereby the difference was statistically significant (P<0.001). In addition, it was revealed that the level of SPOP was associated with histologic type (P=0.003), tumor differentiation (P=0.046), tumor size (P=0.0036), lymph node metastasis (P=0.041) and clinical stages (P=0.046). Furthermore, the overall survival of patients with high SPOP expression was significantly increased compared with that of patients with low SPOP expression (P=0.003). These results revealed that SPOP expression was downregulated in NSCLC tissues and associated with poor prognosis in patients with NSCLC, suggesting that SPOP is an independent prognostic marker candidate for NSCLC.

Speckle-type POZ protein functions as a tumor suppressor in non-small cell lung cancer due to DNA methylation

“…Our previous study found that the expression of SPOP was significantly inhibited in NSCLC tissues compared with that in normal tissues [22]. To determine whether the low SPOP expression in NSCLC is caused by DNA hypermethylation, our study searched the Human Genome Database for the presence of CpG islands in the SPOP promoter using Online software (http://www.urogene.org/methprimer) and found some CpG islands in the vicinity of the transcription start site (Fig.…”

“…However, the regulation mechanism of SPOP expression in NSCLC is still unclear [21]. Intriguingly, our pre-experiment found that SPOP was obviously inhibited in NSCLC tissues compared with that in adjacent normal lung tissues [22], suggesting that SPOP functions as a cancer suppressor gene (TSG). Additionally, Kim et al revealed that SPOP somatic mutations were not harbored in solid tumors, indicating that somatic mutations and decreased SPOP expression might be separate events in NSCLC [20].…”

The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients

“…[14] The same prognostic result was observed in NSCLC, and the downregulation of SPOP expression contributed to poor tumor differentiation and LNM. [11] Additionally, the expression level of SPOP, identified as a prognosis-related biomarker, was significantly lower in CRC tissues than adjacent normal tissues. [13] Although the majority of studies focused on the potential evidence indicating an unfavorable impact of low SPOP expression on clinical outcome, the prognostic value of SPOP in cancer patients is still controversial.…”

The emerging role of SPOP protein in tumorigenesis and cancer therapy

“…LC is one of the leading causes of cancer-related death in the world [82]. Downregulation of SPOP has been observed in non-small cell LC (NSCLC) tissues compared with normal tissues at both the transcriptional and translational levels [83]. Furthermore, the level of SPOP was confirmed to be associated with several clinicopathologic parameters, and a decrease in SPOP was considered a predictor of poor prognosis in patients with NSCLC, suggesting that SPOP could be a potential tumor suppressor in LC [83].…”

“…Downregulation of SPOP has been observed in non-small cell LC (NSCLC) tissues compared with normal tissues at both the transcriptional and translational levels [83]. Furthermore, the level of SPOP was confirmed to be associated with several clinicopathologic parameters, and a decrease in SPOP was considered a predictor of poor prognosis in patients with NSCLC, suggesting that SPOP could be a potential tumor suppressor in LC [83]. The sirtuin (SIRT) family of NAD-dependent protein lysine deacylases has been reported to participate in multiple biological processes such as transcription regulation, metabolism and DNA repair [84][85][86].…”