Elevated FUS/TLS expression is negatively associated with E‑cadherin expression and prognosis of patients with non‑small cell lung cancer

Abstract

Fused in sarcoma/translocated in liposarcoma (FUS/TLS), a ubiquitous and multifunctional DNA and RNA-binding protein, contributes an important function in cancer and neurodegenerative disease; however, its role in lung cancer remains unclear. In the present study, the expression of FUS/TLS in non-small cell lung cancer (NSCLC) and the significance of FUS/TLS for predicting the clinical outcome of patients with NSCLC, was examined. FUS/TLS expression was investigated in NSCLC tissues and their matched adjacent non-tumorous tissues by reverse transcription-quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Tissue microarrays representing 208 patients with NSCLC were used to determine the expression pattern and associations with FUS/TLS using immunohistochemistry. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Data revealed that FUS/TLS expression was elevated in NSCLC tissues compared with corresponding normal tissue mRNA (9.27±0.73 vs. 6.15±0.60) and protein (3.32±0.75 vs. 0.30±0.07) levels. In tissue microarrays, FUS/TLS was highly expressed in 103 (49.5%, 103/208) NSCLC tissues compared with adjacent normal lung tissues (28.4%, 59/208). Overexpression of FUS/TLS was associated with higher tumor node metastasis stage (P=0.016), poorer differentiation (P=0.008), large tumor size (P=0.019) and predicted poor prognosis (P=0.005) in patients with NSCLC. Notably, correlation analysis revealed a significant inverse association between the expression of FUS/TLS and E-cadherin (r=0.51; P=0.036). Furthermore, patients with NSCLC with high FUS/TLS and impaired E-cadherin expression had a notably poor prognosis (P=4.01×10). Thus, the results from the present study indicate that elevated FUS/TLS expression promotes NSCLC progression. FUS/TLS, alone or in combination with E-cadherin, is a novel prognostic predictor for patients with NSCLC.

Clinicopathological significance and prognostic value of E-cadherin expression in non-small cell lung cancer

“…A total of 15 studies were included, [ 7 , 8 , 10 , 11 , 14 , 15 , 19 , 20 , 22 , 23 , 25 – 28 , 33 ] containing 616 patients with low differentiation and 1837 patients with medium and high differentiation. There was mild heterogeneity among studies ( I 2 = 65.0%, P < .…”

Novel Function of lncRNA ADAMTS9-AS2 in Promoting Temozolomide Resistance in Glioblastoma via Upregulating the FUS/MDM2 Ubiquitination Axis

“…The RNA-binding-protein FUS, also known as translocated in liposarcoma (TLS), is a critical regulator during the characteristic pathological features of amyotrophic lateral sclerosis (Sun et al, 2015). Recently, studies have found that FUS mRNA or protein expression is upregulated in liposarcoma (Spitzer et al, 2011), breast cancer (Ke et al, 2016), cervical cancer (Zhu et al, 2018), and FUS promotes malignant progression in non-small cell lung cancer (Xiong D. et al, 2018). Functioning as an oncoprotein, FUS has been proven to be essential for the growth of prostate cancer cells by activating androgen receptor signaling (Haile et al, 2011).…”

MiR-141-3p overexpression suppresses the malignancy of osteosarcoma by targeting FUS to degrade LDHB

“…Combined with results from starBase and our experiments, FUS was identified as the RBP for LDHB. RBP FUS has been discovered to act as a tumor enhancer in several cancers such as thyroid cancer, non-small cell lung cancer and glioma [26][27][28]. Apart from the verified affinity between FUS and LDHB, it was also revealed that FUS could elevate the stability of LDHB mRNA.…”