Testes‑specific protease 50 as an independent risk factor for poor prognosis in patients with non‑small cell lung cancer

Abstract

Testes-specific protease 50 (TSP50) is normally expressed in the testes and is overexpressed in various types of human cancers, including breast cancer, colorectal carcinoma and laryngocarcinoma. However, little has been reported on the association between TSP50 and non-small cell lung cancer (NSCLC). The present study aimed to detect TSP50 expression in 198 strict follow-up cases of paired NSCLC and 15 cases of normal lung parenchymal specimens using immunohistochemical staining. The expression levels of TSP50 were then correlated with the clinicopathological factors of NSCLC to assess its potential diagnostic and prognostic value. The relationship between TSP50 expression and the clinicopathological parameters of NSCLC was evaluated using χ and Fisher's exact tests. Survival rates for the overall population (n=198) were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox's proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. The expression of TSP50 was significantly increased in NSCLC tissue compared with in adjacent non-tumor or normal lung parenchymal tissue (P<0.001). A significant association was revealed between high expression levels of TSP50 and clinicopathological characteristics including tumor differentiation (P=0.012), late tumor status (P=0.004) and late tumor node metastasis stage (P=0.026), as well as a reduced disease free survival (P=0.009) and overall survival rate (P=0.002) in all patients with NSCLC. Multivariate analyses demonstrated that high TSP50 expression in tumor tissues was significantly associated with a shorter disease-free survival rate [hazard ratio (HR) =1.590, 95% confidence interval (CI): 1.035-2.441], and with a shorter overall survival rate (HR=1.814; 95% CI: 1.156-2.846). In conclusion, the present data demonstrated that increased TSP50 protein expression may be a potential predictor of early recurrence and poor prognosis in NSCLC, and that TSP50 expression levels possess the potential to be used as a biomarker and therapeutic target for the treatment of patients with NSCLC.

TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation

“…TSP50 is abnormally highly expressed in various tumor tissues, but is absent in normal tissues 16 – 20 , suggesting a pathogenic role for TSP50 in cancers. TSP50 levels appear to have important clinical implications for cancer patients 18 , 23 , 56 , therefore, we evaluated TSP50 transcription levels via UALCAN database. Analysis results revealed that mRNA expression of TSP50 was significantly higher in TCGA-LIHC tissues than in adjacent normal tissues.…”

Cancer/Testis Antigens as Biomarker and Target for the Diagnosis, Prognosis, and Therapy of Lung Cancer

“…Notably, the median survival times of patients with BORIS-sf6 overexpression or low expression were 26 weeks and 209 weeks, respectively; thus, BORIS-sf6 acts as a powerful prognostic predictor for lung cancer. TSP50 expression levels are higher in the advanced TNM stage in lung cancer patients ( 90 ). Kaplan−Meier analysis shows that disease-free survival and overall survival were significantly lower in lung patients with overexpressed TSP50 compared with those with low TSP50 expression, implying that TSP50 overexpression is associated with poor prognosis in lung cancer patients.…”

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

“…TSP50 participated in multiple malignant processes of cancer, including stimulating cell proliferation via inhibiting activin signaling 269 , promoting invasion and metastasis by inducing EMT 270 . It was also discovered as a potential predictor of early recurrence and poor prognosis in malignancies 271 , and as a unique biomarker or treatment target for a variety of cancer therapies 272 , 273 , 274 , 275 .…”