Development and internal validation of a nine-lncRNA prognostic signature for prediction of overall survival in colorectal cancer patients.
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ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC6286799 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Growing evidence suggests that immune-related genes (IRGs) and long non-coding RNAs (lncRNAs) can serve as prognostic markers of overall survival (OS) in patients with colon cancer. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of prognosis in these patients. Gene expression and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Immune-related lncRNAs were identified by a correlation analysis between IRGs and lncRNAs. In total, 447 samples were divided into a training cohort (224 samples) and a testing cohort (223 samples). Univariate, lasso and multivariate Cox regression analyses identified an immune-related nine-lncRNA signature closely related to OS in colon cancer patients in the training dataset. A risk score formula involving nine immune-related lncRNAs was developed to evaluate the prognostic value of the lncRNA signature in the training dataset. Colon cancer patients with a high risk score had poorer OS than those with a low risk score. A multivariate Cox regression analysis confirmed that the immune-related nine-lncRNA signature could be an independent prognostic factor in colon cancer patients. The results were further confirmed in the testing cohort and the entire TCGA cohort. Furthermore, a gene set enrichment analysis revealed several pathways with significant enrichment in the high- and low-risk groups that may be helpful in formulating clinical strategies and understanding the underlying mechanisms. Finally, a quantitative real-time polymerase chain reaction assay found that the nine lncRNAs were significantly differentially expressed in colon cancer cell lines. The results of this study indicate that this signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in colon cancer patients. These lncRNAs could be potential biomarkers affecting the prognosis of colon cancer.
| S-EPMC7203495 | biostudies-literature
Project description:BackgroundAs a serious challenge for public health, the prognosis of gastric cancer patients is still poor. The current study aimed to develop and validate a prognostic signature to predict the overall survival of gastric cancer patients.Patients and methodsThe dataset in the present study was obtained from The Cancer Genome Atlas database. The present study finally included 343 gastric cancer patients with information on long non-coding RNA (lncRNA) expression and overall survival.ResultsA prognostic model named Eleven-lncRNA signature was constructed according to the expression values of eleven prognostic lncRNA predictors identified by univariate and multivariate Cox regression model. According to time-dependent receiver operating characteristic curves, the Harrell's concordance indexes of Eleven-lncRNA signature were 0.764 (95% CI 0.720-0.808), 0.776 (95% CI 0.732-0.820), and 0.807 (95% CI 0.763-0.851) for 1-year overall survival, 3-year overall survival, and 5-year overall survival respectively in the model group. In the validation group, the Harrell's concordance indexes of Eleven-lncRNA signature were 0.748 (95% CI 0.704-0.792), 0.794 (95% CI 0.750-0.838), and 0.798 (95% CI 0.754-0.842) for 1-year overall survival, 3-year overall survival, and 5-year overall survival respectively. The gastric cancer patients (n=343) in the model group could be stratified into low-risk group (n=171) and high-risk group (n=172) according to the median of Eleven-lncRNA signature score. Kaplan-Meier survival curves showed that the mortality rate in the high-risk group was significantly poorer than that in the low-risk group (P<0.001).ConclusionThe present study constructed and validated a prognostic model named Eleven-lncRNA signature for preoperative individual mortality risk prediction in gastric cancer patients. This Eleven-lncRNA signature can predict the individual mortality risk of gastric cancer patients and is helpful in improving clinical decision making regarding individualized treatment.
| S-EPMC6287660 | biostudies-literature
Project description:The N6-methyladenosine (m6A) RNA modification can modify long non-coding RNAs (lncRNAs), thereby affecting the tumorigenesis and progression of tumors. However, the underlying role of m6A-modified lncRNAs in colorectal cancer (CRC) remains largely unknown. Therefore, our aim was to assess the prognostic value of m6A-modified lncRNAs in CRC patients. The gene expression and clinicopathological data of CRC were extracted from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to investigate the m6A-modified lncRNAs. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance of molecular subtypes was identified. The least absolute shrinkage and selection operator analysis (LASSO) was applied to establish a risk signature. Finally, a prognostic nomogram with risk score and clinicopathological variables was established. In total, 29 m6A-modified lncRNAs were identified as prognostic lncRNAs. Two molecular clusters were identified and significant differences were found with respect to clinicopathological features and prognosis. Cluster1 is associated with poor overall survival (OS), down-regulation of Programmed cell death ligand-1 (PD-L1) expression, lower immune score, and less immune cell infiltration. Then, an m6A-modified lncRNA signature for predicting OS was constructed in the TCGA training cohort. The signature demonstrated favorable prediction performance in both training and validation sets. Compared with low-risk patients, patients with high risk showed worse clinical outcomes, lower immune scores, and downregulated PD-L1 expression. Further analysis indicated that the signature was an independent prognostic indicator, and then a prognostic nomogram based on risk score, tumor location, and tumor stage was established. Our study identified a seven m6A-modified lncRNA signature and established a prognostic nomogram that reliably predicts OS in CRC. These findings may improve the understanding of m6A modifications in CRC and provide insights into the prognosis and treatment strategy of CRC.
| S-EPMC8472391 | biostudies-literature
Project description:Background: This study aimed to explore the biological functions and prognostic role of Epithelial-mesenchymal transition (Epithelial-mesenchymal transition)-related lncRNAs in colorectal cancer (CRC). Methods: The Cancer Genome Atlas database was applied to retrieve gene expression data and clinical information. An EMT-related lncRNA risk signature was constructed relying on univariate Cox regression, Least Absolute Shrinkage and Selector Operation (LASSO) and multivariate Cox regression analysis of the EMT-related lncRNA expression data and clinical information. Then, an individualized prognostic prediction model based on the nomogram was developed and the predictive accuracy and discriminative ability of the nomogram were determined by the receiver operating characteristic curve and calibration curve. Finally, a series of analyses, such as functional analysis and unsupervised cluster analysis, were conducted to explore the influence of independent lncRNAs on CRC. Results: A total of 581 patients were enrolled and an eleven-EMT-related lncRNA risk signature was identified relying on the comprehensive analysis of the EMT-related lncRNA expression data and clinical information in the training cohort. Then, risk scores were calculated to divide patients into high and low-risk groups, and the Kaplan-Meier curve analysis showed that low-risk patients tended to have better overall survival (OS). Multivariate Cox regression analysis indicated that the EMT-related lncRNA signature was significantly associated with prognosis. The results were subsequently confirmed in the validation dataset. Then, we constructed and validated a predictive nomogram for overall survival based on the clinical factors and risk signature. Functional characterization confirmed this signature could predict immune-related phenotype and was associated with immune cell infiltration (i.e., macrophages M0, M1, Tregs, CD4 memory resting cells, and neutrophils), tumor mutation burden (TMB). Conclusions: Our study highlighted the value of the 11-EMT-lncRNA signature as a predictor of prognosis and immunotherapeutic response in CRC.
| S-EPMC8513715 | biostudies-literature
Project description:Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.
| S-EPMC7136791 | biostudies-literature
Project description:Background:Gastric cancer (GC) is one of the most common malignant tumors in the digestive system with high mortality globally. However, the biomarkers that accurately predict the prognosis are still lacking. Therefore, it is important to screen for novel prognostic markers and therapeutic targets. Methods:We conducted differential expression analysis and survival analysis to screen out the prognostic genes. A stepwise method was employed to select a subset of genes in the multivariable Cox model. Overrepresentation enrichment analysis (ORA) was used to search for the pathways associated with poor prognosis. Results:In this study, we designed a seven-gene-signature-based Cox model to stratify the GC samples into high-risk and low-risk groups. The survival analysis revealed that the high-risk and low-risk groups exhibited significantly different prognostic outcomes in both the training and validation datasets. Specifically, CGB5, IGFBP1, OLFML2B, RAI14, SERPINE1, IQSEC2, and MPND were selected by the multivariable Cox model. Functionally, PI3K-Akt signaling pathway and platelet-derived growth factor receptor (PDGFR) were found to be hyperactive in the high-risk group. The multivariable Cox regression analysis revealed that the risk stratification based on the seven-gene-signature-based Cox model was independent of other prognostic factors such as TNM stages, age, and gender. Conclusion:In conclusion, we aimed at developing a model to predict the prognosis of gastric cancer. The predictive model could not only effectively predict the risk of GC but also be beneficial to the development of therapeutic strategies.
| S-EPMC7468614 | biostudies-literature
Project description:Cumulative studies have shown that RNA binding proteins (RBPs) play an important role in numerous malignant tumors and are related to the occurrence and progression of tumors. However, the role of RBPs in kidney renal clear cell carcinoma (KIRC) is not fully understood. In this study, we first downloaded gene expression data and corresponding clinical information of KIRC from the Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) database, respectively. A total of 137 differentially expressed RBPs (DERBPs) were then identified between normal and tumor tissue, including 38 downregulated and 99 upregulated RBPs. Nine RBPs (EIF4A1, RPL36A, EXOSC5, RPL28, RPL13, RPS19, RPS2, EEF1A2, and OASL) were served as prognostic genes and exploited to construct a prognostic model through survival analysis. Kaplan-Meier curves analysis showed that the low-risk group had a better survival outcome when compared with the high-risk group. The area under the curve (AUC) value of the prognostic model was 0.713 in the TCGA data set (training data set), 0.706 in the ICGC data set, and 0.687 in the GSE29609 data set, respectively, confirming a good prognostic model. The prognostic model was also identified as an independent prognostic factor for KIRC survival by performing cox regression analysis. In addition, we also built a nomogram relying on age and the prognostic model and internal validation in the TCGA data set. The clinical benefit of the prognostic model was revealed by decision curve analysis (DCA). Gene set enrichment analysis revealed several crucial pathways (ERBB signaling pathway, pathways in cancer, MTOR signaling pathway, WNT signaling pathway, and TGF BETA signaling pathway) that may explain the underlying mechanisms of KIRC. Furthermore, potential drugs for KIRC treatment were predicted by the Connectivity Map (Cmap) database based on DERBPs, including several important drugs, such as depudecin and vorinostat, that could reverse KIRC gene expression, which may provide reference for the treatment of KIRC. In summary, we developed and validated a robust nine-RBP signature for KIRC prognosis prediction. A nomogram with risk score and age can be applied to promote the individualized prediction of overall survival in patients with KIRC. Moreover, the two drugs depudecin and vorinostat may contribute to KIRC treatment.
| S-EPMC7566920 | biostudies-literature
Project description:Background and objectiveAs a common cancer type in women, cervical cancer remains one of the leading causes of cancer-associated mortalities word wide. Recent evidence has demonstrated the regulatory role of a large number of long non-coding RNAs (lncRNAs) in cervical cancer. Here, we aimed to identify new biomarkers that related with the recurrence through comprehensive bioinformatics analysis.MethodsFirstly, we collected online lncRNA expression data of cervical cancer patients which were divided into training, validation, and test set. Then we developed a nine-lncRNA signature from training set by conducting LASSO Cox regression model along with 10-fold cross validation. The prognostic value of this risk score was validated in all the three sets using Kaplan-Meier analysis, C-index, time-dependent ROC curves and dynamic AUC. Biological function of these lncRNAs in cervical cancer cells were evaluated by performing gene ontology biological process enrichment and Kyoto Encyclopedia of Genes and Genomes signaling pathways analysis.ResultsAccording to the results, a higher predict accuracy was observed in the nine-lncRNA signature than that of FIGO stage in all the three sets. Stratified analysis also demonstrated that the nine-lncRNA signature can predict the recurrence of cervical cancer within FIGO stage. The potential mechanisms underlying the nine-lncRNAs from the signature were also identified according to the gene enrichment analysis.ConclusionIn the present article, we provided a reliable prognostic tool to facilitate the individual management of patients with cervical cancer after treatment.
| S-EPMC6456668 | biostudies-literature
Project description:BACKGROUND:There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC). METHODS:RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature. RESULTS:A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P?<?0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P?<?0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-?B signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. CONCLUSION:The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.
| S-EPMC7493157 | biostudies-literature
Project description:Background: Pancreatic cancer is highly lethal and aggressive with increasing trend of mortality in both genders. An effective prediction model is needed to assess prognosis of patients for optimization of treatment. Materials and Methods: Seven datasets of mRNA expression and clinical data were obtained from gene expression omnibus (GEO) database. Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas pancreatic ductal adenocarcinoma (TCGA-PAAD) dataset. Differentially expressed genes (DEGs) between pancreatic tumor and normal tissue were identified by integrated analysis of multiple GEO datasets. Univariate and Lasso Cox regression analyses were applied to identify overall survival-related DEGs and establish a prognostic gene signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index) and calibration curve. GSE62452 and GSE57495 were used for external validation. Gene set enrichment analysis (GSEA) and tumor immunity analysis were applied to elucidate the molecular mechanisms and immune relevance. Multivariate Cox regression analysis was used to identify independent prognostic factors in pancreatic cancer. Finally, a prognostic nomogram was established based on the TCGA PAAD dataset. Results: A nine-gene signature comprising MET, KLK10, COL17A1, CEP55, ANKRD22, ITGB6, ARNTL2, MCOLN3, and SLC25A45 was established to predict overall survival of pancreatic cancer. The ROC curve and C-index indicated good performance of the nine-gene signature at predicting overall survival in the TCGA dataset and external validation datasets relative to classic AJCC staging. The nine-gene signature could classify patients into high- and low-risk groups with distinct overall survival and differentiate tumor from normal tissue. Univariate Cox regression revealed that the nine-gene signature was an independent prognostic factor in pancreatic cancer. The nomogram incorporating the gene signature and clinical prognostic factors was superior to AJCC staging in predicting overall survival. The high-risk group was enriched with multiple oncological signatures and aggressiveness-related pathways and associated with significantly lower levels of CD4+ T cell infiltration. Conclusion: Our study identified a nine-gene signature and established a prognostic nomogram that reliably predict overall survival in pancreatic cancer. The findings may be beneficial to therapeutic customization and medical decision-making.
| S-EPMC6776930 | biostudies-literature