scholarly journals A Prognostic Model Based on Immune-Related Long Non-Coding RNAs for Patients With Cervical 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 < 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 11 (1) ◽  
Author(s):  
Jian Zhang ◽  
Nan Ding ◽  
Yongxing He ◽  
Chengbin Tao ◽  
Zhongzhen Liang ◽  
...  

AbstractThe research is executed to analyze the connection between genomic instability-associated long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We set a prognostic model up and explored different risk groups' features. The clinical datasets and gene expression profiles of 307 patients have been downloaded from The Cancer Genome Atlas database. We established a prognostic model that combined somatic mutation profiles and lncRNA expression profiles in a tumor genome and identified 35 genomic instability-associated lncRNAs in cervical cancer as a case study. We then stratified patients into low-risk and high-risk groups and were further checked in multiple independent patient cohorts. Patients were separated into two sets: the testing set and the training set. The prognostic model was built using three genomic instability-associated lncRNAs (AC107464.2, MIR100HG, and AP001527.2). Patients in the training set were divided into the high-risk group with shorter overall survival and the low-risk group with longer overall survival (p < 0.001); in the meantime, similar comparable results were found in the testing set (p = 0.046), whole set (p < 0.001). There are also significant differences in patients with histological grades, FIGO stages, and different ages (p < 0.05). The prognostic model focused on genomic instability-associated lncRNAs could predict the prognosis of cervical cancer patients, paving the way for further research into the function and resource of lncRNAs, as well as a key approach to customizing individual care decision-making.


2020 ◽  
Author(s):  
Jianfeng Zheng ◽  
Jinyi Tong ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu

Abstract Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores(IS)based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1740-1740
Author(s):  
Oleg Shukhov ◽  
Ekaterina Chelysheva ◽  
Anna Petrova ◽  
Anastasiya Bykova ◽  
Irina Nemchenko ◽  
...  

Abstract Background: A large number of tyrosine kinase inhibitors (TKI) discontinuation studies has shown that about 50% of chronic myeloid leukemia (CML) patients (pts) after TKI cessation lose a major molecular response (MMR) and should return to therapy. Despite the fact that, after TKI resumption, almost all patients re-achieve deep molecular remission, facilitating a more accurate selection process for therapy cessation remains topical. Aim: Develop a prognostic model for the better selection of CML patients for TKI discontinuation. Methods: The base for the training set was the Russian multicenter prospective study RU-SKI on the discontinuation of TKI in pts with CML and deep molecular response (DMR). Ninety-eight CML pts with chronic phase (CP), TKI therapy for at least three years and a stable DMR (BCR-ABL<0.01%) for at least two years were enrolled. Seven Pts with a previous history of unsuccessful treatment-free remission (TFR) were excluded from the analysis. The BCR-ABL level was evaluated by RQ-PCR according to the international scale (IS). The schedule of molecular tests was as follows: monthly during the first six months (mo) after TKI cessation, every two mo from six to 12 mo and every three mo thereafter. Treatment by the same TKI was resumed in case of MMR loss (BCR-ABL>0.1%). We used the Kaplan-Meier method for calculating the probability of TFR. Univariate analyses were performed using the log-rank test to identify prognostic factors for TFR. Variables found to be significant at the p<0.10 level were entered into a proportional hazards regression analysis. We categorized each independently significant factor into two groups, depending on the optimal cutoff level obtained by ROC analysis and the minimum P-value approach. The next step was a second multivariate analysis including categorized variables. A favorable factor from each variable was scored as 1, while the adverse factor was scored proportionally to the level of hazard ratio. The cumulative score for each patient was calculated. Patients were allocated to either a high or a low risk group concerning MMR loss after the cutoff level was determined by ROC analysis. The validation set included a series of 48 retrospective cases of discontinued patients selected according to RU-SKI inclusion criteria. Results: Baseline characteristics of the training set (n=91): male: 48%; median (Mе) age at TKI cessation 46 years (range 22 to 80); Me duration of TKI therapy 8.3 years (range three to 16.2); Me duration of DMR 3.2 years (range two to 10.7). Therapy before treatment cessation: imatinib in 63 (69%) pts, second-generation (2G) TKI in 28 (31%) pts. Me follow-up time after TKI cessation was 14 mo (range three to 36). Probability of TFR was 55% after 12 mo of follow-up. We analyzed the following factors: age, gender, history of previous resistance to imatinib, type and line of TKI, duration of therapy, length of DMR, depth of molecular response before cancellation, Sokal risk group. Age, Sokal risk group, duration of therapy and depth of molecular response were found to be independently significant factors and included in the survival prognostic model (Table 1). 73% (n=66) of pts scored 5.5 points or less and were assigned to the low risk group. The probability of TFR was 64% and 33% for the low risk and high risk groups, respectively (p=0.001) (Figure 1). Baseline characteristics of validation set (n=48): male: 36%; Ме age at TKI cessation 46 years (range 22 to 76); Me duration of TKI therapy six years (range 3.5 to 13.2); Me duration of DMR 2.8 years (range two to 10). Therapy before treatment stopped: imatinib in 31 (65%) pts, 2G TKI in 17 (35%) pts. Me follow-up time after TKI cessation was 36 mo (range six to 116). Probability of TFR was 47% after 30 mo of follow-up. In the validation set, 77% (n=37) of pts were assigned to the low risk group. The probability of TFR was 56% and 18% for the low risk and high risk groups, respectively (p=0.007) (Figure 2). Conclusion: RU-SKI prognostic model is effective in prediction of successful TFR and can be used for better selection of CML pts for TKI discontinuation. Disclosures Shukhov: Novartis: Other: provided consultations and performed lectures ; Bristol Myers Squibb: Other: provided consultations and performed lectures . Chelysheva:Novartis: Other: provided consultations and performed lectures; Fusion Pharma: Other: provided consultations ; Bristol Myers Squibb: Other: provided consultations and performed lectures. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ziwei Wang ◽  
Yan Liu ◽  
Jun Zhang ◽  
Rong Zhao ◽  
Xing Zhou ◽  
...  

Background. Endometrial cancer is among the most common malignant tumors threatening the health of women. Recently, immunity and long noncoding RNA (lncRNA) have been widely examined in oncology and shown to play important roles in oncology. Here, we searched for immune-related lncRNAs as prognostic biomarkers to predict the outcome of patients with endometrial cancer. Methods. RNA sequencing data for 575 endometrial cancer samples and immune-related genes were downloaded from The Cancer Genome Atlas (TCGA) database and gene set enrichment analysis (GSEA) gene sets, respectively. Immune-related lncRNAs showing a coexpression relationship with immune-related genes were obtained, and Cox regression analysis was performed to construct the prognostic model. Survival, independent prognostic, and clinical correlation analyses were performed to evaluate the prognostic model. Immune infiltration of endometrial cancer samples was also evaluated. Functional annotation of 12 immune-related lncRNAs was performed using GSEA software. Prognostic nomogram and survival analysis for independent prognostic risk factors were performed to evaluate the prognostic model and calculate the survival time based on the prognostic model. Results. Twelve immune-related lncRNAs (ELN-AS1, AC103563.7, PCAT19, AF131215.5, LINC01871, AC084117.1, NRAV, SCARNA9, AL049539.1, POC1B-AS1, AC108134.4, and AC019080.5) were obtained, and a prognostic model was constructed. The survival rate in the high-risk group was significantly lower than that in the low-risk group. Patient age, pathological grade, the International Federation of Gynecology and Obstetrics (FIGO) stage, and risk status were the risk factors. The 12 immune-related lncRNAs correlated with patient age, pathological grade, and FIGO stage. Principal component analysis and functional annotation showed that the high-risk and low-risk groups separated better, and the immune status of the high-risk and low-risk groups differed. Nomogram and receiver operating characteristic (ROC) curves effectively predicted the prognosis of endometrial cancer. Additionally, age, pathological grade, FIGO stage, and risk status were all related to patient survival. Conclusion. We identified 12 immune-related lncRNAs affecting the prognosis of endometrial cancer, which may be useful as therapeutic targets and molecular biomarkers.


2021 ◽  
Author(s):  
Bo Liu ◽  
Tingting Fu ◽  
Ping He ◽  
Chenyou Du ◽  
Ke Xu

Purpose: To identify differentially expressed immune-related genes (DEIRGs) and construct a model with survival-related DEIRGs for evaluating the prognosis of patients with pancreatic cancer (PC). Methods: Six microarray gene expression datasets of PC from the Gene Expression Omnibus (GEO) and ImmPort were used to identify DEIRGs. RNA sequencing and clinical data from The Cancer Genome Atlas Program-Pancreatic Adenocarcinoma (TCGA-PAAD) database were used to establish the prognostic model. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to determine the final variables of the prognostic model. The median risk score was used as the cut-off value to classify samples into low- and high-risk groups. The prognostic model was further validated using an internal validation set of TCGA and an external validation set of GSE62452. Results: In total, 142 DEIRGs were identified from six GEO datasets, 47 were survival-related DEIRGs. A prognostic model comprising five genes (i.e., ERAP2, CXCL9, AREG, DKK1, and IL20RB) was established. High-risk patients had poor survival compared with low-risk patients. The 1-, 2-, 3-year area under the receiver operating characteristic curve of the model reached 0.85, 0.87, and 0.93, respectively. Additionally, the prognostic model reflected the infiltration of neutrophils and dendritic cells. The expression of most characteristic immune checkpoints was significantly higher in the high-risk group versus the low-risk group.  Conclusions: The five-gene prognostic model showed reliably predictive accuracy. This model may provide useful information for immunotherapy and facilitate personalized monitoring for patients with PC.


2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Yao Peng ◽  
Hui Wang ◽  
Qi Huang ◽  
Jingjing Wu ◽  
Mingjun Zhang

Abstract Background Long noncoding RNAs (lncRNAs) are important regulators of gene expression and can affect a variety of physiological processes. Recent studies have shown that immune-related lncRNAs play an important role in the tumour immune microenvironment and may have potential application value in the treatment and prognosis prediction of tumour patients. Epithelial ovarian cancer (EOC) is characterized by a high incidence and poor prognosis. However, there are few studies on immune-related lncRNAs in EOC. In this study, we focused on immune-related lncRNAs associated with survival in EOC. Methods We downloaded mRNA data for EOC patients from The Cancer Genome Atlas (TCGA) database and mRNA data for normal ovarian tissue from the Genotype-Tissue Expression (GTEx) database and identified differentially expressed genes through differential expression analysis. Immune-related lncRNAs were obtained through intersection and coexpression analysis of differential genes and immune-related genes from the Immunology Database and Analysis Portal (ImmPort). Samples in the TCGA EOC cohort were randomly divided into a training set, validation set and combination set. In the training set, Cox regression analysis and LASSO regression were performed to construct an immune-related lncRNA signature. Kaplan–Meier survival analysis, time-dependent ROC curve analysis, Cox regression analysis and principal component analysis were performed for verification in the training set, validation set and combination set. Further studies of pathways and immune cell infiltration were conducted through Gene Set Enrichment Analysis (GSEA) and the Timer data portal. Results An immune-related lncRNA signature was identified in EOC, which was composed of six immune-related lncRNAs (KRT7-AS, USP30-AS1, AC011445.1, AP005205.2, DNM3OS and AC027348.1). The signature was used to divide patients into high-risk and low-risk groups. The overall survival of the high-risk group was lower than that of the low-risk group and was verified to be robust in both the validation set and the combination set. The signature was confirmed to be an independent prognostic biomarker. Principal component analysis showed the different distribution patterns of high-risk and low-risk groups. This signature may be related to immune cell infiltration (mainly macrophages) and differential expression of immune checkpoint-related molecules (PD-1, PDL1, etc.). Conclusions We identified and established a prognostic signature of immune-related lncRNAs in EOC, which will be of great value in predicting the prognosis of clinical patients and may provide a new perspective for immunological research and individualized treatment in EOC.


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 &lt; 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 &lt; 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 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Jianfeng Zheng ◽  
Benben Cao ◽  
Xia Zhang ◽  
Zheng Niu ◽  
Jinyi Tong

Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune-related lncRNAs (IRLs) of CC has never been reported. This study is aimed at establishing an IRL signature for patients with CC. A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson correlation analysis between the immune score and lncRNA expression ( p < 0.01 ). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values ( p < 0.05 ) were identified which demonstrated an ability to stratify patients into the low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low-risk group showed longer overall survival (OS) than those in the high-risk group in the training set, valid set, and total set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four-IRL signature in predicting the one-, two-, and three-year survival rates was larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four IRLs in the development of CC were ascertained preliminarily.


2021 ◽  
Author(s):  
Wenxi Wang ◽  
Na Li ◽  
Lin Shen ◽  
Qin Zhou ◽  
Zhanzhan Li ◽  
...  

Abstract Purpose: Breast cancer (BC) has a relatively high morbidity and mortality for women. The research about BC prognosis is significant. Autophagy is an essential process for tumor progression, which could play its role with lncRNA, a kind of ncRNA that have regulatory roles in multiple tumors. Therefore, constructing an autophagy-related prognostic model for breast cancer is meaningful.Methods: We download data from the TCGA and HADb. Pearson correlation analysis was performed to excavate autophagy-related lncRNA. Then with gene expression difference analysis, etc. we explored the relationship between clinical features and the signature. We applied Cytoscape as well as KEGG, etc. to explore expression condition. And the autophagy status of our signature was investigated by GSEA, etc. We also searched the immune distinction by CIBERSORTx to extend our study and preliminarily verified our study in the end.Results: Firstly, we got an independent autophagy-related lncRNA prognostic model, by which BC patients were divided into high- and low-risk groups. We found that the OS of high-risk group is significantly lower than that of low-risk group, which was identical to those within various clinical subgroups. Then, the KEGG and GO analysis enriched several pathways including autophagy. PCA and GSEA analysis demonstrated the autophagy status. Several distinguishing immune cell types in separated groups were revealed by immunity analysis. Then the verification in the end proved the feasibility of our signature.Conclusion: In this study, we acquired an independent autophagy-related lncRNA signature involving 12 lncRNAs, which contributes to the prediction of prognosis of BC patients.


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