Key Points Question What is the immunogenomic landscape of osteosarcoma? Findings In this genetic association study based on 84 samples from The Cancer Genome Atlas, 14 immune-related genes associated with survival in osteosarcoma were identified. Meaning These findings suggest that a diagnostic risk score based on immune-related gene expression profiles may be useful to planning individualized therapies for osteosarcoma.

AimHomeobox (HOX) genes and their protein products have been found to function as oncogenes in the progression of many cancers. But the role of Homeobox C10 (HOXC10) in osteosarcoma (OS) still remains less understood. In this study, we firstly determine the biologic functions of HOXC10 in OS.Materials and methodsWe examined the expression of HOXC10 in OS tissues by quantitative real-time polymerase chain reaction and Western blot assays. We investigated the effects of HOXC10 on cell proliferation, apoptosis and caspase 3 activity in three OS cell lines by RNA interference, Cell Counting Kit-8, flow cytometry and colorimetric assays.ResultsWe found that HOXC10 was elevated in OS tissues. Silencing HOXC10 significantly inhibited cell proliferation, induced cell apoptosis and increased the expression and activity of caspase 3. The resistance assay further suggested that HOXC10 affected cell growth and apoptosis through regulating the expression and activity of caspase 3.ConclusionHOXC10 might function as an oncogene in OS by regulating the expression and activity of caspase 3.

No abstract

No abstract

Aims: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. Methods: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. Results: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 × 10⁹ pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 μg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. Conclusions: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.