Role of Epithelial Cell Transforming Sequence 2 (ECT2) in Predicting Prognosis of Osteosarcoma

Abstract

Background:Osteosarcoma is a major bone malignancy in children and young adults, and it is highly heterogeneous. The clinical outcome of osteosarcoma is individual-dependent due to different genetic and pathological profiles. Although chemotherapy in combination with surgery has significantly improved the survival of localized disease, the prognostic improvement for metastatic patients is less marked. ECT2 (epithelial cell transforming sequence 2) is a transforming protein that can interact with Rho-like proteins of the Ras family and has been proven as an ontogenetic protein in cancer cell lines. We studied the clinical significance of ECT2 in osteosarcoma and explored its underlying oncogenic mechanisms. Material/Methods:The protein expression pattern of ECT2 in osteosarcoma was investigated by immunohistochemical staining, and its association with clinicopathological characteristics was initially explored. The significance of ECT2 in predicting patient prognosis was verified by univariate and multivariate analyzes. Cellular experiments were conducted to explore underlying mechanisms of ECT2 in regulating osteosarcoma progression. Results:High ECT2 expression was correlated with tumor metastasis and poor overall survival of osteosarcoma patients. ECT2 promotes cell invasion by modulating EMT process. Conclusions:ECT2 is an independent prognostic factor for osteosarcoma and it can upregulate the metastatic capacity of osteosarcoma cells.

Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis

“…The oncogene ECT2 is a guanine nucleotide exchange factor (GEF)of the Rho family members of small GTPases and essential for signal transduction pathways involved in the regulation of cytokinesis. Chen et al [57] . showed that overexpression of ECT2 promoted the metastasis of osteosarcoma by regulating the EMT process.…”

Composite bottlebrush mechanics: α-internexin fine-tunes neurofilament network properties

“…14,38 Such crosslinkers should also affect the inter-filament distance. 13,30,39,40 In order to find potential cross-linking sites we undertake an electrostatic ''handshake'' analysis of the NF tails. 30 We evaluate short-range electrostatic attractive interactions, between tails, using a coarse-grained model; where segments engage in a zipper-like electrostatic interaction.…”

Clinicopathological and prognostic significance of epithelial cell transforming sequence 2 expression in cancers: a systematic review and meta-analysis

“…Xu et al [55] have reported that the downregulation of ECT2 by miR-223 induces the expression of p21 and p27, which restrain cell cycle progression and proliferation in osteosarcoma cells. Furthermore, according to Chen et al [19], ECT2 could promote osteosarcoma cell invasion by facilitating the epithelialmesenchymal transition. In addition to miRNAs, several signalling molecules have been identified as up-stream regulators of ECT2 expression in cancer cells; these promote cancer progression in an ECT2-dependent manner.…”

“…A total of 19 published articles with 21 studies enrolling 5,305 patients met the inclusion criteria for the meta-analysis [11,15,[19][20][21][22][23][24][25][32][33][34][35][36][37][38][39][40][41]. A flow diagram of the detailed literature selection process is displayed in Figure 1.…”

“…Indeed, growing evidence suggests that ECT2 is frequently overexpressed in various cancers and serves as an oncogene [15][16][17][18]. Moreover, numerous clinical studies have shown that high ECT2 expression is associated with adverse clinicopathological characteristics, such as poor tumour differentiation, larger tumour size, positive lymphatic metastasis, and advanced disease stage, and as well as an unfavourable prognosis in multiple type of cancers [11,15,[19][20][21][22][23][24][25], further suggesting that it is a promising prognostic biomarker in cancers. Nevertheless, these previous studies are limited by sample sizes or study methodologies.…”