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Prognostic PredictionUsing a StemnessIndex-RelatedSignature in a Cohortof Gastric Cancer Xiaowei ChenDawei ZhangFei Jiang2020 год

Prognostic Prediction Using a Stemness Index-Related Signature in a Cohort of Gastric Cancer
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Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: With characteristic self-renewal and multipotent differentiation, cancer stem cells (CSCs) have a crucial influence on the metastasis, relapse and drug resistance of gastric cancer (GC). However, the genes that participates in the stemness of GC stem cells have not been identified.The mRNA expression-based stemness index (mRNAsi) was analyzed with differential expressions in GC. The weighted gene co-expression network analysis (WGCNA) was utilized to build a co-expression network targeting differentially expressed genes (DEG) and discover mRNAsi-related modules and genes. We assessed the association between the key genes at both the transcription and protein level. Gene Expression Omnibus (GEO) database was used to validate the expression levels of the key genes. The risk model was established according to the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Furthermore, we determined the prognostic value of the model by employing Kaplan-Meier (KM) plus multivariate Cox analysis.GC tissues exhibited a substantially higher mRNAsi relative to the healthy non-tumor tissues. Based on WGCNA, 17 key genes (ARHGAP11A, BUB1, BUB1B, C1orf112, CENPF, KIF14, KIF15, KIF18B, KIF4A, NCAPH, PLK4, RACGAP1, RAD54L, SGO2, TPX2, TTK, and XRCC2) were identified. These key genes were clearly overexpressed in GC and validated in the GEO database. The protein-protein interaction (PPI) network as assessed by STRING indicated that the key genes were tightly connected. After LASSO analysis, a nine-gene risk model (BUB1B, NCAPH, KIF15, RAD54L, KIF18B, KIF4A, TTK, SGO2, C1orf112) was constructed. The overall survival in the high-risk group was relatively poor. The area under curve (AUC) of risk score was higher compared to that of clinicopathological characteristics. According to the multivariate Cox analysis, the nine-gene risk model was a predictor of disease outcomes in GC patients (HR, 7.606; 95% CI, 3.037-19.051; P < 0.001). We constructed a prognostic nomogram with well-fitted calibration curve based on risk score and clinical data.The 17 mRNAsi-related key genes identified in this study could be potential treatment targets in GC treatment, considering that they can inhibit the stemness properties. The nine-gene risk model can be employed to predict the disease outcomes of the patients.
Год издания: 2020
Авторы: Xiaowei Chen, Dawei Zhang, Fei Jiang, Yan Shen, Xin Li, Xueju Hu, Pingmin Wei, Xiaobing Shen
Издательство: Frontiers Media
Источник: Frontiers in Molecular Biosciences
Ключевые слова: Ferroptosis and cancer prognosis, Cancer-related molecular mechanisms research, RNA modifications and cancer
Другие ссылки: Frontiers in Molecular Biosciences (PDF)
Frontiers in Molecular Biosciences (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)