Dataset Information

IASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin in vitro.

ABSTRACT: The oncogenetic function of inhibitory member of the apoptosis stimulating protein of p53 family (iASPP) in chordoma is unclear and remains to elucidate. The expression of iASPP in chordoma tissues and cells, its correlation to clinicopathological parameters and the effect on the patients' prognosis were evaluated. Cellular proliferation, invasion and cisplatin-response were observed after the iASPP knockdown or overexpression in vitro. Co-Immunoprecipitation assay was used to explore the interaction between iASPP and p53. The regulation of miRNA-124 on the expression and apoptotic function of iASPP was explored after transiently transfecting cells with miRNA-124 mimics or inhibitor. Results indicated that iASPP overexpressed in chordoma tissues and cells. Its overexpression was associated with tumor invasion and local recurrence, and was predictive of patients' poor prognosis. Cells with iASPP-silence showed a decreased ability of proliferation and invasion, but an increasing sensitivity to cisplatin. Besides, iASPP could combine with p53 in either endogenous or exogenous detection. Post-transcriptionally, miRNA-124 negatively regulated the expression of iASPP, which further led to the changes of apoptosis-related proteins. Thus, iASPP overexpression is associated with the clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and the sensitivity to cisplatin.

SUBMITTER: Ma Y

PROVIDER: S-EPMC5620263 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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iASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin <i>in vitro</i>.

Ma Yunlong Y Zhu Bin B Liu Xiaoguang X Liu Zhongjun Z Jiang Liang L Wei Feng F Yu Miao M Wu Fengliang F Zhou Hua H Xu Nanfang N Liu Xiao X Yong Lei L Wang Yongqiang Y Wang Peng P Liang Chen C He Guanping G

Oncotarget 20170811 40

The oncogenetic function of inhibitory member of the apoptosis stimulating protein of p53 family (iASPP) in chordoma is unclear and remains to elucidate. The expression of iASPP in chordoma tissues and cells, its correlation to clinicopathological parameters and the effect on the patients' prognosis were evaluated. Cellular proliferation, invasion and cisplatin-response were observed after the iASPP knockdown or overexpression <i>in vitro</i>. Co-Immunoprecipitation assay was used to explore the ...[more]

PMID: 28978123

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Project description:BACKGROUND:Currently, the measurement of immune cells in previous studies is usually subjective, and no immune-based prognostic model has been established for chordoma. In this study, we sought to simultaneously measure tumor-infiltrating lymphocyte (TIL) subtypes in chordoma samples using an objective method and develop an immune risk score (IRS) model for survival prediction. METHODS:Multiplexed quantitative immunofluorescence staining was used to determine the TIL levels in the tumoral and stromal subareas of 114 spinal chordoma specimens (54 in the training and 60 in the validation cohort) for programmed death-1 (PD-1), CD3, CD8, CD20 (where CD is cluster of differentiation), and FOXP3. Flow cytometry was performed to validate the immunofluorescence assay for lymphocyte measurement on an additional five fresh chordoma specimens. Subsequently, the IRS model was built using the least absolute shrinkage and selection operator (LASSO) Cox regression method. RESULTS:Flow cytometry and quantitative immunofluorescence showed similar lymphocytic percentages and TIL subpopulation proportions in the fresh tumor specimens. With the training data, the LASSO model identified four immune features for IRS construction: tumoral FOXP3, tumoral PD-1, stromal FOXP3, and stromal CD8. In both cohorts, a high IRS was significantly associated with tumoral programmed cell death-1 ligand 1 expression, Enneking inappropriate tumor resection, and surrounding muscle invasion by tumor. Multivariate Cox regression and stratified analysis in the two cohorts revealed that the IRS was an independent predictor and could effectively separate patients with similar Enneking staging into different risk subgroups, with significantly different survival rates. Further receiver operating characteristic analysis found that the IRS classifier had a better prognostic value than the traditional clinicopathological factors and compensated for the deficiency of Enneking staging for outcome prediction. More importantly, a nomogram based on the IRS and clinical predictors showed adequate performance in estimating disease recurrence and survival of patients. CONCLUSIONS:These data support the use of the IRS signature as a reliable prognostic tool in spinal chordoma and may facilitate individualized therapy decision making for patients.

Dataset Information

IASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin in vitro.

Publications

iASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin <i>in vitro</i>.

Similar Datasets

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