Background and AimHepatocellular carcinoma is a common malignant tumor of the digestive system with a poor prognosis. The high recurrence rate and metastasis after surgery reduce the survival time of patients. Therefore, assessing the overall survival of patients with hepatocellular carcinoma after hepatectomy is critical to clinicians’ clinical decision-making. Conventional hepatocellular carcinoma assessment systems (such as tumor lymph node metastasis and Barcelona clinical hepatocellular carcinoma) are obviously insufficient in assessing the overall survival rate of patients. This research is devoted to the development of nomogram assessment tools to assess the overall survival probability of patients undergoing liver resection.MethodsWe collected the clinical and pathological information of 438 hepatocellular carcinoma patients undergoing surgery from The Cancer Genome Atlas (TCGA) database, then excluded 87 patients who did not meet inclusion criteria. Univariate and multivariate analyses were performed on patient characteristics and related pathological factors. Finally, we developed a nomogram model to predict patient’s prognosis.ResultsA retrospective analysis of 438 consecutive samples from the TCGA database of patients with hepatocellular carcinoma who underwent potentially curative liver resections. Six risk factors were included in the final model. In the training set, the discriminative ability of the nomogram was very good (concordance index = 0.944), and the external verification method (concordance index = 0.962) was used for verification. At the same time, the internal and external calibration of the model was verified, showing that the model was well calibrated. The calibration between the evaluation of the nomogram and the actual observations was good. According to the patient’s risk factors, we determined the patient’s Kaplan-Meyer survival analysis curve. Finally, the clinical decision curve was used to compare the benefits of two different models in evaluating patients’ clinical outcomes.ConclusionsThe nomogram can be used to evaluate the post-hepatectomy 1-, 3-, and 5-year survival rates of patients with hepatocellular carcinoma. The Kaplan-Meyer curve can intuitively display the survival differences among patients with various risk factors. The clinical decision curve is a good reference guide for clinical application.
BackgroundHepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality worldwide. Immunotherapy has emerged as an increasingly important cancer treatment modality. However, the potential relationship between immune genes and HCC still needs to be explored. The purpose of this study is to construct a new prognostic risk signature to predict the prognosis of HCC patients based on the expression of immune-related genes (IRGs) and explore its potential mechanism.MethodsWe analyzed the gene expression data of 332 HCC patient samples and 46 adjacent normal tissues samples (Solid Tissue Normal including cirrhotic tissue) in The Cancer Genome Atlas (TCGA) database and clinical characteristics. We analyzed the gene expression data, identified differentially expressed IRGs in HCC tissues, filtered IRGs with prognostic value to construct an IRG signature, and classified patients into high and low gene expression groups based on the expression of IRGs in their tumor tissues. We also investigated the potential molecular mechanisms of IRGs through a bioinformatics approach using Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis and Gene Ontology (GO) database analysis. Differentially expressed IRGs associated with significant clinical outcomes (SIRGs) were identified by univariate Cox regression analysis. An immune-related risk score model (IRRSM) was established based on Lasso Cox regression analysis and multivariate Cox regression analysis. Based on the IRRSM, the immune score of the patients was calculated, and the patients were divided into high-risk and low-risk patients according to the median score, and the differences in survival between the two groups were compared. Then, the correlation analysis between the IRRSM and clinical characteristics was performed, and the IRRSM was validated using the International Cancer Genome Consortium (ICGC) database.ResultsThe IRRSM was eventually constructed and confirmed to be an independent prognostic model for HCC patients. The IRRSM was shown to be positively correlated with the infiltration of four types of immune cells.ConclusionOur results showed that some SIRGs have potential value for predicting the prognosis and clinical outcomes of HCC patients. IRGs affect the prognosis of HCC patients by regulating the tumor immune microenvironment (TIME). This study provides a new insight for immune research and treatment strategies in HCC patients.
Growing evidence implicates that miRNAs can interact with long non-coding RNAs (lncRNAs) to regulate target mRNAs through competitive interactions. However, this mechanism that regulate tumorigenesis and cancer progression remains largely unexplored. Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs), which play a significant role in regulating gene expression. The purpose of our study was to determine potential lncRNA biomarkers to predict the prognosis of HCC by comprehensive analysis of a ceRNA network. The edgeR package was used to obtain the differentially expressed RNA datasets by analyzing 370 HCC tissues and 50 adjacent non-HCC tissues from The Cancer Genome Atlas (TCGA). Through investigating the differentially expressed between HCC tissues and adjacent non-HCC tissues, a total of 947 lncRNAs, 52 miRNAs, and 1,650 mRNAs were obtained. The novel constructed ceRNA network incorporated 99 HCC-specific lncRNAs, four miRNAs, and 55 mRNAs. Survival analysis identified 22 differentially expressed mRNAs, four miRNAs, and nine lncRNAs which were associated with overall survival (OS) time in HCC (p < 0.05), and further exploration was performed to assess the correlation of these differentially expressed genes with tumor stage. The Interpretation of the potential functions of these differentially expressed genes in HCC was realized by Gene ontology (GO) and KEGG pathway enrichment analyses. Seven lncRNAs were confirmed based on univariate Cox regression analysis, lasso COX regression analysis and multivariate Cox regression analysis to construct a predictive model in HCC patients which were related to the prognosis of OS. In summary, ceRNAs contributed to explore the mechanism of tumorigenesis and development, and a model with seven lncRNAs might be potential biomarker to predict the prognosis of HCC. These findings supported the need to studies on the mechanisms involved in the regulation of HCC by ceRNAs.
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