Background Necroptosis is a novel programmed cell death mode independent on caspase. A number of studies have revealed that the induction of necroptosis could act as an alternative therapeutic strategy for drug-resistant tumors as well as affect tumor immune microenvironment. Methods Gene expression profiles and clinical data were downloaded from XENA-UCSC (including The Cancer Genome Atlas and Genotype-Tissue Expression), Gene Expression Omnibus, International Cancer Genome Consortium and Chinese Glioma Genome Atlas. We used non-negative matrix factorization method to conduct tumor classification. The least absolute shrinkage and selection operator regression was applied to establish risk models, whose prognostic effectiveness was examined in both training and testing sets with Kaplan–Meier analysis, time-dependent receiver operating characteristic curves as well as uni- and multi-variate survival analysis. Principal Component Analysis, t-distributed Stochastic Neighbor Embedding and Uniform Manifold Approximation and Projection were conducted to check the risk group distribution. Gene Set Enrichment Analyses, immune infiltration analysis based on CIBERSORT, EPIC, MCPcounter, ssGSEA and ESTIMATE, gene mutation and drug sensitivity between the risk groups were also taken into consideration. Results There were eight types of cancer with at least ten differentially expressed necroptosis-related genes which could influence patients’ prognosis, namely, adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), acute myeloid leukemia (LAML), brain lower grade glioma (LGG), pancreatic adenocarcinoma (PAAD), liver hepatocellular carcinoma (LIHC), skin cutaneous melanoma (SKCM) and thymoma (THYM). Patients could be divided into different clusters with distinct overall survival in all cancers above except for LIHC. The risk models could efficiently predict prognosis of ACC, LAML, LGG, LIHC, SKCM and THYM patients. LGG patients from high-risk group had a higher infiltration level of M2 macrophages and cancer-associated fibroblasts. There were more CD8+ T cells, Th1 cells and M1 macrophages in low-risk SKCM patients’ tumor microenvironment. Gene mutation status and drug sensitivity are also different between low- and high-risk groups in the six cancers. Conclusions Necroptosis-related genes can predict clinical outcomes of ACC, LAML, LGG, LIHC, SKCM and THYM patients and help to distinguish immune infiltration status for LGG and SKCM.
Background: The collaborative efforts of the Chinese Childhood Cancer Organization (CCCG) have led to an improved understanding of NB biology, standardized classification, and stratification strategies, thereby improving outcomes in China. We aimed to assess the NB-2015 protocol developed by the CCCG in 2015 and to evaluate the degree of impact of autologous peripheral blood stem cell transplantation (APBSCT). Methods: This study enrolled NB patients from seven medical centers in China between 2015 and 2018. In this paper, we retrospectively analyzed the clinical characteristics of 161 patients and used their effect on survival as an outcome measure. Results: The 3-year event-free survival (EFS) rates were 95.5%, 91.6%, and 51.1% in the low-, medium-, and high-risk groups, respectively. In total, 3 out of 7 (42.8%) patients with stage 2B disease, none of whom had MYCN amplifications, relapsed. A total of 47 of the 78 patients in the high-risk group underwent external-beam radiation to the primary tumor bed (dose ranging from 18 to 36 Gy). There was a significant difference in efficacy between patients who received radiation therapy and those who did not (3-year OS P = 0.041). Within the high-risk group, The 3-year EFS rates of the patients with and without APBSCT were 72.6% and 37.1%, respectively (P=0.008).Conclusions: This study showed that satisfactory results were obtained without fatal complications using the NB-2015 protocol. Chemotherapy should be intensified in the stage 2B group. APBSCT can effectively improve the survival rate of NB patients, especially high-risk patients.
Objective This study aimed to analyse the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China. Methods The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen at the Tianjin Medical University Cancer Institute & Hospital were reviewed. The baseline clinicopathological characteristics and prognosis of were analysed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared. Results The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and overall survival (OS) rates for the transplantation group and the nontransplantation group were 65.5% vs. 41.3% (P=0.023) and 77.1% vs. 57.9% (P=0.03), respectively. There was no difference in the distribution of baseline clinical case characteristics between the single transplantation group and the tandem transplantation group (P>0.05), and there was no significant difference in EFS and OS between the two groups (P>0.05). Conclusion Based on this pretreatment programme, autologous peripheral blood stem cell transplantation is safe and tolerable and significantly improves the prognosis of children in the high-risk group. The value of tandem autologous stem cell transplantation is worthy of further discussion, which should consider various aspects such as the transplantation plan and the patient’s state.
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