Abstract
Osteosarcoma (OS) is the most common primary bone cancer in childhood. OS is an aggressive disease, and metastatic patients evolve with very poor clinical outcomes. Genetically, OSs are extremely complex tumors, and the related metastatic process is not well understood in terms of the biology of the disease. In this context, long non-coding RNAs (lncRNAs) have emerged as an important class of gene expression regulators that play key roles in the invasion and metastasis of several human tumors. Here, we evaluated the expression of HULC, which is an lncRNA that is associated with the tumor metastatic process, and assessed its potential role as a prognostic marker in OS. HULC expression was evaluated in primary OS samples using real-time RT-PCR. HULC expression status was determined by receiver operating characteristic (ROC) analysis, and its association with survival was assessed using the Kaplan-Meier method. The HULC expression level was not significantly associated with the clinicopathological characteristics of the OS patients. However, our data demonstrated that higher levels of expression of HULC were associated with lower survival rates in OS patients, both in terms of overall and event-free survival. Elevated HULC expression was associated with poor clinical outcomes among the OS patients, which suggests that HULC could be a potential prognostic biomarker in OS.
Highlights
Primary bone tumors represent 5–6% of all tumors of childhood and adolescence (0–19 years), and osteosarcomas (OSs) are the most common primary bone tumor in this age group [1]
We observed that Hepatocellular carcinoma up-regulated long non-coding RNA (HULC) expression was not significantly associated with the evaluated clinicopathological characteristics of the osteosarcoma patients (Table 3)
Association of HULC expression with the prognoses of the osteosarcoma patients The patients with higher HULC expression presented 5-year overall survival rate of 26.0% compared with 75.4% for those with low expression (p = 0.016)
Summary
Primary bone tumors represent 5–6% of all tumors of childhood and adolescence (0–19 years), and osteosarcomas (OSs) are the most common primary bone tumor in this age group [1]. Metastatic disease sites commonly exhibit resistance to treatment, which results in a low patient survival rate of approximately 20% over five years [3,4]. High levels of the expressions of the MAPK7 and MAP2K4 genes have been reported to be significantly associated with metastasis in OS [9]. In this context, long non-coding RNAs (lncRNA) are emerging as important molecular markers of metastatic disease in several human cancers [10,11,12,13]. We evaluated the expression of HULC in primary osteosarcoma samples at diagnosis and its association with the clinicopathological characteristics of OS Brazilian patients. We evaluated the role of HULC expression as a potential prognostic marker in OS
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