Background: Soft tissue sarcomas (STS) are heterogeneous tumors derived from mesenchymal cells that differentiate into soft tissues. The prognosis of patients who present with an STS is influenced by the regulation of a complex gene network.Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with STS (Samples = 156).Results: Among the 11 modules identified, the black and blue modules were highly correlated with STS. However, using preservation analysis, the black module demonstrated low preservation, therefore the blue module was chosen as the module of interest. Furthermore, a total of 20 network hub genes were identified in the blue module, 12 of which were also hub nodes in the protein-protein interaction network of the module genes. Following additional verification, 4 of 12 genes (RRM2, BUB1B, CENPF, and KIF20A) demonstrated poorer overall survival and disease-free survival rate in the test datasets. In addition, gene set enrichment analysis (GSEA) demonstrated that samples with a high level of blue module eigengene (ME) were enriched in cell cycle and metabolism associated signaling pathways.Conclusion: In summary, co-expression network analysis identified four hub genes associated with prognosis for STS, which may diminish the prognosis by influencing cell cycle and metabolism associated signaling pathways.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an effective chemotherapeutic agent that specifically impairs cancer cells while sparing normal cells; however, some cancer cells develop resistance to TRAIL. Here, we identified Andrographolide, a diterpenoid lactone derived from a traditional herbal medicine Andrographis paniculata, as an ideal sensitizer for TRAIL to overcome bladder cancer. Our results showed that combination treatment of Andro and TRAIL retarded growth, attenuated proliferation, decreased colony formation, inhibited migration and promoted caspases-mediated apoptosis in T24 cells. Additionally, the sensitization by Andro is achieved through up-regulation of death receptors (DR4 and DR5) of TRAIL in a p53-dependent manner. Crucially, Andro is also capable of inactivating NF-κB signaling pathway via transcriptional down-regulation p65/RelA, which is further contributed to enhancement of TRAIL-mediated cytotoxicity. These results indicated that non-toxic doses of Andrographolide sensitized bladder cancer cells to TRAIL-mediated apoptosis, suggesting it as an effective therapeutic agent for TRAIL resistant human bladder cancers.
Prostate cancer (PCa) survival markedly decreases with the occurrence of distant metastasis, and treatment decisions can be influenced by metastasis site, and affect patient survival outcomes. The aim of the present study was to evaluate the potential prognostic value of metastasis to specific sites and the prognostic value of prostatectomy in patients with only bone metastasis, and to determine potential risk factors for bone metastasis in prostatic adenocarcinoma using large scale clinical data. The Surveillance, Epidemiology and End Results (SEER) database (2010–2013) was queried via the SEER*Stat (version 8.3.4) program. A total of 210,730 prostatic adenocarcinoma patients were identified from the SEER database between January 2010 and December 2013. Univariate and multivariate Cox regression analysis and Kaplan-Meier curves were used for survival comparisons with corresponding 95% confidence intervals. Patients with PCa with only liver metastatic lesions had worse overall and cancer-specific survival rates compared with those patients with only bone or lung metastasis. Multivariate Cox regression analysis revealed that age <50 years, married status, T1 and T3 tumor stage according to Tumor-Node-Metastasis (TNM) staging system from the 7th AJCC cancer staging manual, and prostatectomy were associated with better overall survival and cancer-specific survival in patients with only bone metastasis. Binary logistic regression analysis revealed that unmarried status, African descent and undifferentiated histological grade were risk factors for PCa bone metastasis. Prostatic adenocarcinoma patients with only liver metastasis had worse prognostic outcomes compared with patients with other distant organ metastases. Prostatectomy improved the 3-year survival rate in stage IV PCa patients and stage IV PCa patients with only bone metastasis. These findings were based on large-scale clinical data and can provide novel perspectives for the treatment of patients with advanced prostate adenocarcinoma.
We concluded that MLN4924 induces apoptosis and cell cycle arrest. These findings implied that MLN4924 provides a novel strategy for the treatment of RCC.
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