scholarly journals Construction of Prognostic Risk Prediction Model of Oral Squamous Cell Carcinoma Based on Nine Survival-Associated Metabolic Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhen-Dong Huang ◽  
Yang-Yang Yao ◽  
Ting-Yu Chen ◽  
Yi-Fan Zhao ◽  
Chao Zhang ◽  
...  

The aim was to investigate the independent prognostic factors and construct a prognostic risk prediction model to facilitate the formulation of oral squamous cell carcinoma (OSCC) clinical treatment plan. We constructed a prognostic model using univariate COX, Lasso, and multivariate COX regression analysis and conducted statistical analysis. In this study, 195 randomly obtained sample sets were defined as training set, while 390 samples constituted validation set for testing. A prognostic model was constructed using regression analysis based on nine survival-associated metabolic genes, among which PIP5K1B, NAGK, and HADHB significantly down-regulated, while MINPP1, PYGL, AGPAT4, ENTPD1, CA12, and CA9 significantly up-regulated. Statistical analysis used to evaluate the prognostic model showed a significant different between the high and low risk groups and a poor prognosis in the high risk group (P < 0.05) based on the training set. To further clarify, validation sets showed a significant difference between the high-risk group with a worse prognosis and the low-risk group (P < 0.05). Independent prognostic analysis based on the training set and validation set indicated that the risk score was superior as an independent prognostic factor compared to other clinical characteristics. We conducted Gene Set Enrichment Analysis (GSEA) among high-risk and low-risk patients to identify metabolism-related biological pathways. Finally, nomogram incorporating some clinical characteristics and risk score was constructed to predict 1-, 2-, and 3-year survival rates (C-index = 0.7). The proposed nine metabolic gene prognostic model may contribute to a more accurate and individualized prediction for the prognosis of newly diagnosed OSCC patients, and provide advice for clinical treatment and follow-up observations.

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing-Qing Xu ◽  
Qing-Jie Li ◽  
Cheng-Long Huang ◽  
Mu-Yan Cai ◽  
Mei-Fang Zhang ◽  
...  

PurposeWe aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN).MethodsIn total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study.ResultsWe extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (P<0.001), and in the validation set, the 5-year OS rate was 38.1% (95% CI: 17.9%-81.1%) for the high-risk group and 43.1% (95% CI: 30.0%-61.9%) for the low-risk group (P=0.26). Multivariable analysis revealed that IHC score, T stage, and primary tumor site were independent variables for predicting OS (all P<0.05). We developed a nomogram incorporating clinicopathological risk factors (primary site and T stage) and the IHC score to predict 3-, 5-, and 10-year OS.ConclusionsA nomogram was generated and confirmed to be of clinical value. Our IHC classifier integrating five IHC markers could help clinicians make decisions and determine optimal treatments for patients with MMHN.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Yang ◽  
Mingyang Feng ◽  
LiangLiang Bai ◽  
Mengxi Zhang ◽  
Kexun Zhou ◽  
...  

Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.


2020 ◽  
Author(s):  
Lumeng Luo ◽  
Minghe Lv ◽  
Xuan Li ◽  
Tiankui Qiao ◽  
Kuaile Zhao ◽  
...  

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dakui Luo ◽  
Zezhi Shan ◽  
Qi Liu ◽  
Sanjun Cai ◽  
Qingguo Li ◽  
...  

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen-gene metabolic signature was developed to divide patients into a high-risk group and a low-risk group. Patients in the high-risk group presented poorer prognosis compared to the low-risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism-related pathways. To sum up, our study described a novel seventeen-gene metabolic signature for prognostic prediction of colon cancer.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4848-4848
Author(s):  
Michele Malagola ◽  
Crisitina Skert ◽  
Marco Vignetti ◽  
Alfonso Piciocchi ◽  
Giovanni Martinelli ◽  
...  

Abstract Abstract 4848 Objectives: the prognosis of patients with cytogenetically normal acute myeloid leukemia (CN-AML) is highly variable and can be influenced by several clinical and biological variables. Nevertheless, some biological data may be conflicting and difficult to combine with the clinical ones. Methods: in order to propose a simple scoring system, we retrospectively analysed the clinical data of 337 patients newly diagnosed with CN-AMLs, aged less than 65 years, consecutively treated in eleven hematological Italian Centres from 1990 to 2005. Two hundred nineteen patients (65%) received a fludarabine-based induction regimen. All the other patients received a conventional induction regimen, including cytarabine, one anthracycline with or without etoposide. Univariate and multivariate analysis on event free survival and overall survival (EFS and OS) were performed. Patients addressed to allogeneic stem cell transplantation were censored at the time of transplant. Factors found to be significant in univariate analysis were tested in multivariate analysis. A numerical score was derived from the regression coefficients of each independent prognostic variable. The Prognostic Index Score (PIS) for each patient was then calculated by totalling up the score of each independent variable. Patients could thus be stratified into low-risk (score = 0–1), intermediate-risk (score = 2) and high-risk group (score grater than 3). The score obtained in this group of patients (training set) was then tested on 193 patients with newly diagnosed with CN-AMLs, aged less than 65 years, enrolled in the GIMEMA LAM99p clinical trial (validation set). Results: the clinical variables that were independent prognostic factors on EFS in the training set of patients were: age > 50 yrs (regression coefficient: 0.39, HR 1.5, score = 1), secondary AML (regression coefficient: 0.90, HR 2.5, score = 2) and WBC > 20 × 10^9/L (regression coefficient: 0.83, HR 2.3, score = 2). For what concerns the OS, the same variables showed the followings statistical data: age > 50 yrs (regression coefficient: 0.48, HR 1.6, score = 1), secondary AML (regression coefficient: 0.99, HR 2.7, score = 2) and WBC > 20 × 10^ 9/L (regression coefficient: 0.87, HR 2.4, score = 2). In the training set of patients, the median EFS was 22, 12 and 8 months in the low, intermediate and high-risk group (p<0.0001). The median OS was not reached in the low-risk group and was 20 and 10 months in the intermediate and high-risk group (p<0.0001). In the validation set of patients, the median EFS was 66, 16 and 3 months in the low, intermediate and high-risk group (p<0.0001). The median OS was 66, 16 and 4 months in the low, intermediate and high-risk group (p<0.0001). Conclusions: this simple and reproducible prognostic score may be useful for clinical-decision making in newly diagnosed patients with CN-AMLs, aged less than 65 yrs. Moreover, it can be clinically useful when the molecular prognostic markers are lacking (e.g. in emerging laboratories of some developing countries) or give contradictory results. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Peng Gu ◽  
Lei Zhang ◽  
Ruitao Wang ◽  
Wentao Ding ◽  
Wei Wang ◽  
...  

Background: Female breast cancer is currently the most frequently diagnosed cancer in the world. This study aimed to develop and validate a novel hypoxia-related long noncoding RNA (HRL) prognostic model for predicting the overall survival (OS) of patients with breast cancer.Methods: The gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 200 hypoxia-related mRNAs were obtained from the Molecular Signatures Database. The co-expression analysis between differentially expressed hypoxia-related mRNAs and lncRNAs based on Spearman’s rank correlation was performed to screen out 166 HRLs. Based on univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis in the training set, we filtered out 12 optimal prognostic hypoxia-related lncRNAs (PHRLs) to develop a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic curves, area under the curve, and univariate and multivariate Cox regression analyses were used to test the predictive ability of the risk model in the training, testing, and total sets.Results: A 12-HRL prognostic model was developed to predict the survival outcome of patients with breast cancer. Patients in the high-risk group had significantly shorter median OS, DFS (disease-free survival), and predicted lower chemosensitivity (paclitaxel, docetaxel) compared with those in the low-risk group. Also, the risk score based on the expression of the 12 HRLs acted as an independent prognostic factor. The immune cell infiltration analysis revealed that the immune scores of patients in the high-risk group were lower than those of the patients in the low-risk group. RT-qPCR assays were conducted to verify the expression of the 12 PHRLs in breast cancer tissues and cell lines.Conclusion: Our study uncovered dozens of potential prognostic biomarkers and therapeutic targets related to the hypoxia signaling pathway in breast cancer.


2021 ◽  
Author(s):  
Chen-jie Qiu ◽  
Xue-bing Wang ◽  
Zi-ruo Zheng ◽  
Chao-zhi Yang ◽  
Kai Lin ◽  
...  

Abstract Background: The purpose of this study was to identify ferroptosis-related genes (FRGs) associated with the prognosis of pancreatic cancer and to construct a prognostic model based on FRGs. Methods: Based on pancreatic cancer data obtained from The Cancer Genome Atlas database, we established the prognostic model from 232 FRGs. A nomogram was constructed by combining the prognostic model and clinicopathological features. Gene Expression Omnibus datasets and tissue samples obtained from our center were utilized to validate the model. Relationship between risk score and immune cell infiltration was explored by CIBERSORT and TIMER.Results: The prognostic model was established based on four FRGs (ENPP2, ATG4D, SLC2A1 and MAP3K5) and can be an independent risk factor in pancreatic cancer (HR 1.648, 95% CI 1.335-2.035, p < 0.001). Based on the median risk score, patients were divided into a high-risk group and a low-risk group. The prognosis of the low-risk group was significantly better than that of the high-risk group. In the high-risk group, patients treated with chemotherapy had a better prognosis. The nomogram showed that the model was the most important element. Gene set enrichment analysis identified three key pathways, namely, TGFβ signaling, HIF signaling pathway and adherens junction. The prognostic model can also affect the immune cell infiltration, such as macrophages M0, M1, CD4+T cell and CD8+T cell. Conclusion: A ferroptosis-related prognostic model can be employed to predict the prognosis of pancreatic cancer. Ferroptosis can be an important marker and immunotherapy can be a potential therapeutic target for pancreatic cancer.


2020 ◽  
Vol 11 ◽  
Author(s):  
Peijie Chen ◽  
Yuting Gao ◽  
Si Ouyang ◽  
Li Wei ◽  
Min Zhou ◽  
...  

Objectives: The study is performed to analyze the relationship between immune-related long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We constructed a prognostic model and explored the immune characteristics of different risk groups.Methods: We downloaded the gene expression profiles and clinical data of 227 patients from The Cancer Genome Atlas database and extracted immune-related lncRNAs. Cox regression analysis was used to pick out the predictive lncRNAs. The risk score of each patient was calculated based on the expression level of lncRNAs and regression coefficient (β), and a prognostic model was constructed. The overall survival (OS) of different risk groups was analyzed and compared by the Kaplan–Meier method. To analyze the distribution of immune-related genes in each group, principal component analysis and Gene set enrichment analysis were carried out. Estimation of STromal and Immune cells in MAlignant Tumors using Expression data was performed to explore the immune microenvironment.Results: Patients were divided into training set and validation set. Five immune-related lncRNAs (H1FX-AS1, AL441992.1, USP30-AS1, AP001527.2, and AL031123.2) were selected for the construction of the prognostic model. Patients in the training set were divided into high-risk group with longer OS and low-risk group with shorter OS (p = 0.004); meanwhile, similar result were found in validation set (p = 0.013), combination set (p &lt; 0.001) and patients with different tumor stages. This model was further confirmed in 56 cervical cancer tissues by Q-PCR. The distribution of immune-related genes was significantly different in each group. In addition, the immune score and the programmed death-ligand 1 expression of the low-risk group was higher.Conclusions: The prognostic model based on immune-related lncRNAs could predict the prognosis and immune status of cervical cancer patients which is conducive to clinical prognosis judgment and individual treatment.


2021 ◽  
Vol 104 (1) ◽  
pp. 003685042110065
Author(s):  
Jing Wan ◽  
Peigen Chen ◽  
Yu Zhang ◽  
Jie Ding ◽  
Yuebo Yang ◽  
...  

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ling-Feng Liu ◽  
Qing-Song Li ◽  
Yin-Xiang Hu ◽  
Wen-Gang Yang ◽  
Xia-Xia Chen ◽  
...  

PurposeThe role of radiotherapy, in addition to chemotherapy, has not been thoroughly determined in metastatic non-small cell lung cancer (NSCLC). The purpose of the study was to investigate the prognostic factors and to establish a model for the prediction of overall survival (OS) in metastatic NSCLC patients who received chemotherapy combined with the radiation therapy to the primary tumor.MethodsThe study retrospectively reviewed 243 patients with metastatic NSCLC in two prospective studies. A prognostic model was established based on the results of the Cox regression analysis.ResultsMultivariate analysis showed that being male, Karnofsky Performance Status score &lt; 80, the number of chemotherapy cycles &lt;4, hemoglobin level ≤120 g/L, the count of neutrophils greater than 5.8 ×109/L, and the count of platelets greater than 220 ×109/L independently predicted worse OS. According to the number of risk factors, patients were further divided into one of three risk groups: those having ≤ 2 risk factors were scored as the low-risk group, those having 3 risk factors were scored as the moderate-risk group, and those having ≥ 4 risk factors were scored as the high-risk group. In the low-risk group, 1-year OS is 67.7%, 2-year OS is 32.1%, and 3-year OS is 19.3%; in the moderate-risk group, 1-year OS is 59.6%, 2-year OS is 18.0%, and 3-year OS is 7.9%; the corresponding OS rates for the high-risk group were 26.2%, 7.9%, and 0% (P&lt;0.001) respectively.ConclusionMetastatic NSCLC patients treated with chemotherapy in combination with thoracic radiation may be classified as low-risk, moderate-risk, or high-risk group using six independent prognostic factors. This prognostic model may help design the study and develop the plans of individualized treatment.


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