scholarly journals A Five-MicroRNA Signature Predicts the Prognosis in Nasopharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Shixiong Wu ◽  
Cen Zhang ◽  
Jing Xie ◽  
Shuang Li ◽  
Shuo Huang

BackgroundThere is no effective prognostic signature that could predict the prognosis of nasopharyngeal carcinoma (NPC).MethodsWe constructed a prognostic signature based on five microRNAs using random forest and Least Absolute Shrinkage And Selection Operator (LASSO) algorithm on the GSE32960 cohort (N = 213). We verified its prognostic value using three independent external validation cohorts (GSE36682, N = 62; GSE70970, N = 246; and TCGA-HNSC, N = 523). Through principal component analysis, receiver operating characteristic curve analysis, and C-index calculation, we confirmed the predictive accuracy of this prognostic signature.ResultsWe calculated the risk score based on the LASSO algorithm and divided the patients into high- and low-risk groups according to the calculated optimal cutoff value. The patients in the high-risk group tended to have a worse prognosis outcome and chemotherapy response. The time-dependent receiver operating characteristic curve showed that the 1-year overall survival rate of the five-microRNA signature had an area under the curve of more than 0.83. A functional annotation analysis of the five-microRNA signature showed that the patients in the high-risk group were usually accompanied by activation of DNA repair and MYC-target pathways, while the patients in the low-risk group had higher immune-related pathway signals.ConclusionsWe constructed a five-microRNA prognostic signature, which could accurately predict the prognosis of nasopharyngeal carcinoma, and constructed a nomogram that could conveniently predict the overall survival of patients.

2016 ◽  
Vol 34 (20) ◽  
pp. 2366-2371 ◽  
Author(s):  
Arti Hurria ◽  
Supriya Mohile ◽  
Ajeet Gajra ◽  
Heidi Klepin ◽  
Hyman Muss ◽  
...  

Purpose Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). Patients and Methods Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. Results The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). Conclusion This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.


2021 ◽  
Author(s):  
Jianyu Zhao ◽  
Bo Liu ◽  
Xiaoping Li

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.Methods: The gene expression profile for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors.Results: We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor.Conclusion: Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11911
Author(s):  
Lei Liu ◽  
Huayu He ◽  
Yue Peng ◽  
Zhenlin Yang ◽  
Shugeng Gao

Background The prognosis of patients for lung adenocarcinoma (LUAD) is known to vary widely; the 5-year overall survival rate is just 63% even for the pathological IA stage. Thus, in order to identify high-risk patients and facilitate clinical decision making, it is vital that we identify new prognostic markers that can be used alongside TNM staging to facilitate risk stratification. Methods We used mRNA expression from The Cancer Genome Atlas (TCGA) cohort to identify a prognostic gene signature and combined this with clinical data to develop a predictive model for the prognosis of patients for lung adenocarcinoma. Kaplan-Meier curves, Lasso regression, and Cox regression, were used to identify specific prognostic genes. The model was assessed via the area under the receiver operating characteristic curve (AUC-ROC) and validated in an independent dataset (GSE50081) from the Gene Expression Omnibus (GEO). Results Our analyses identified a four-gene prognostic signature (CENPH, MYLIP, PITX3, and TRAF3IP3) that was associated with the overall survival of patients with T1-4N0-2M0 in the TCGA dataset. Multivariate regression suggested that the total risk score for the four genes represented an independent prognostic factor for the TCGA and GEO cohorts; the hazard ratio (HR) (high risk group vs low risk group) were 2.34 (p < 0.001) and 2.10 (p = 0.017). Immune infiltration estimations, as determined by an online tool (TIMER2.0) showed that CD4+ T cells were in relative abundance in the high risk group compared to the low risk group in both of the two cohorts (both p < 0.001). We established a composite prognostic model for predicting OS, combined with risk-grouping and clinical factors. The AUCs for 1-, 3-, 5- year OS in the training set were 0.750, 0.737, and 0.719; and were 0.645, 0.766, and 0.725 in the validation set. The calibration curves showed a good match between the predicted probabilities and the actual probabilities. Conclusions We identified a four-gene predictive signature which represents an independent prognostic factor and can be used to identify high-risk patients from different TNM stages of LUAD. A new prognostic model that combines a prognostic gene signature with clinical features exhibited better discriminatory ability for OS than traditional TNM staging.


2021 ◽  
Author(s):  
Jianyu Zhao ◽  
Bo Liu ◽  
Xiaoping Li

Abstract Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.Results: We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor.Conclusion: Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.


2020 ◽  
Author(s):  
Jianyu Zhao ◽  
Bo Liu ◽  
Xiaoping Li

Abstract Background Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients. Methods The gene expression profile for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors. Results We identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specificity. Furthermore, the TF-risk score was an independent prognostic factor. Conclusions Taken together, we identified a 13-TF prognostic marker to predict overall survival in ACC patients.


2014 ◽  
Vol 120 (5) ◽  
pp. 1168-1181 ◽  
Author(s):  
Daryl J. Kor ◽  
Ravi K. Lingineni ◽  
Ognjen Gajic ◽  
Pauline K. Park ◽  
James M. Blum ◽  
...  

Abstract Background: Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients. Methods: This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer–Lemeshow goodness-of-fit test were used to assess model performance. Results: Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and ≥30 breaths/min), Fio2 greater than 35%, and Spo2 less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84. Conclusions: In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6061 ◽  
Author(s):  
Zhiqiao Zhang ◽  
Qingbo Liu ◽  
Peng Wang ◽  
Jing Li ◽  
Tingshan He ◽  
...  

Background Colorectal cancer remains a serious public health problem due to the poor prognosis. In the present study, we attempted to develop and validate a prognostic signature to predict the individual mortality risk in colorectal cancer patients. Materials and Methods The original study datasets were downloaded from The Cancer Genome Atlas database. The present study finally included 424 colorectal cancer patients with wholly gene expression information and overall survival information. Results A nine-lncRNA prognostic signature was built through univariate and multivariate Cox proportional regression model. Time-dependent receiver operating characteristic curves in model cohort demonstrated that the Harrell’s concordance indexes of nine-lncRNA prognostic signature were 0.768 (95% CI [0.717–0.819]), 0.778 (95% CI [0.727–0.829]) and 0.870 (95% CI [0.819–0.921]) for 1-year, 3-year and 5-year overall survival respectively. In validation cohort, the Harrell’s concordance indexes of nine-lncRNA prognostic signature were 0.761 (95% CI [0.710–0.812]), 0.801 (95% CI [0.750–0.852]) and 0.883 (95% CI [0.832–0.934]) for 1-year, 3-year and 5-year overall survival respectively. According to the median of nine-lncRNA prognostic signature score in model cohort, 424 CRC patients could be stratified into high risk group (n = 212) and low risk group (n = 212). Kaplan–Meier survival curves showed that the overall survival rate of high risk group was significantly lower than that of low risk group (P < 0.001). Discussion The present study developed and validated a nine-lncRNA prognostic signature for individual mortality risk assessment in colorectal cancer patients. This nine-lncRNA prognostic signature is helpful to evaluate the individual mortality risk and to improve the decision making of individualized treatments in colorectal cancer patients.


2020 ◽  
Author(s):  
zhaoqun Deng ◽  
Xiao-yu Su ◽  
Xin Zhu ◽  
Qian Zhao ◽  
Jin-ming Ke ◽  
...  

Abstract Background: PTEN, known as a classical tumor suppressor, has been reported to be down-expressed in acute myeloid leukemia (AML) and affected the progression of AML patients. CircRNAs, an emerging type of non-coding RNAs, could act as competing endogenous RNAs (ceRNAs) and has been reported to regulate the expression of PTEN through sponging miRNA in many solid tumors. But there are rarely studies focused on the role of circ-PTEN in AML. Our research was aimed to investigate the expression level of circ_0002232, one of circular RNAs of PTEN, reveal the clinical significance and potential ceRNA interaction network in AML of it.Methods: Circ_0002232 expression in 117 AML patients and 48 controls was detected by using Real-time quantitative PCR. The diagnostic value of circ_0002232 expression was evaluated by receiver operating characteristic curve. Kaplan-Meier curves were used to analyse the impact of circ_0002232 for overall survival. CeRNA network of circ_0002232 was predicted by using interaction prediction websites.Results: Compared with controls, circ_0002232 was notably low-expressed in AML (P<0.001). According to the result of receiver operating characteristic curve, circ_0002232 expression could distinguish AML patients from controls (P<0.001). There were significant differences in patients’ age (P=0.002), FAB classifications (P=0.025), white blood cell count (P=0.034) and platelet count (P=0.047) between low-expressed circ_0002232 group and high-expressed circ_00022332 group. Moreover, there was a positive correlation between circ_0002232 expression and patients’ age (Pearson r=0.256, P=0.0053). Interestingly, we found that patients in low-expressed circ_0002232 group had better overall survival both in whole AML (P=0.019) and non-APL AML (P=0.044). Remarkably, the expression of circ_0002232 was positively correlated with PTEN (Pearson r=0.769, P<0.001). Furthermore, there was a negative correlation in AML between circ_0002232 and miR-92a-3p (Pearson r=-0.262, P=0.032), miR-92a-3p and PTEN (Pearson r=-0.358, P=0.019). Interaction prediction websites revealed that circ_0002232 might regulate the expression of PTEN through sponging miR-92a-3p and affect the process of AML.Conclusions: Circ_0002232, one of circRNAs of PTEN, was remarkably down-regulated in AML and could act as a promising biomarker for the diagnosis of AML. In addition, there might be a potential ceRNA interaction network of circ_0002232/miR-92a-3p/PTEN in AML.


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