High expression of RRM2 mediated by non-coding RNAs correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma
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ABSTRACT:
SUBMITTER: Mao G
PROVIDER: S-EPMC9330188 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: With a high incidence and dismal survival rate, hepatocellular carcinoma (HCC) tops the list of the world's most frequent malignant tumors. Immunotherapy is a new approach to cancer treatment, and its effect on prolonging overall survival (OS) varies from patient to patient. For a more effective prognosis and treatment of HCC, we are committed to identifying immune infiltration-related long non-coding RNAs (IIRLs) with prognostic value in hepatocellular carcinoma. Methods: In our study, we calculated immune scores of 369 hepatocellular carcinoma samples from the Cancer Genome Atlas (TCGA) database by using an estimation algorithm, and obtained long non-coding RNAs (lncRNAs) associated with immune infiltration by using Weighted Gene Co-expression Network analysis (WGCNA). For training cohort, univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis were used to determine prognostic IIRLs, we established a prognostic IIRLs signature. By testing cohort and entire cohort, we confirmed that the signature is practical. The prognosis of people with different clinicopathological stages and risk scores were predicted by the nomogram we constructed. In addition, Immune cell infiltration analysis and prediction of therapeutic drugs were performed. Results: 93 IIRLs were obtained by WGCNA. Furthermore, the prognostic value of these IIRLs were evaluated by using univariate Cox, Lasso and multivariate Cox analysis. Four IIRLs were used to create a signature with a prognosis. Time-related receiver operating characteristic (ROC) curve revealed that this model had an acceptable prognostic value for HCC patients. By using univariate and multivariate Cox regression analysis, this risk score has been shown to be an independent prognostic factor for HCC. The nomogram we made showed good predictions. Except for that, the treatment with immune checkpoint inhibitors (ICI) was likely to be more effective for low-risk patients. Conclusion: Based on four IIRLs, a prognostic signature was created in this research showed good accuracy in predicting OS. This study also provided valuable references for Immunotherapy of hepatocellular carcinoma.
| S-EPMC9773198 | biostudies-literature
Project description:CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P<0.001 for RFS) were associated with shorter OS and RFS. Patients in the CXCL17low group had significantly lower 5-year recurrence rate compared with patients in the CXCL17high group (peritumoral: 53.1% vs. 77.7%, P<0.001, intratumoral: 58.6% vs. 73.0%, P = 0.001, respectively). Multivariate Cox proportional hazards analysis identified peritumoral CXCL17 as an independent prognostic factor for both OS (hazard ratio [HR] = 2.066, 95% confidence interval [CI] = 1.296-3.292, P = 0.002) and RFS (HR = 1.844, 95% CI = 1.218-2.793, P = 0.004). Moreover, CXCL17 expression was associated with more CD68 and less CD4 cell infiltration (both P<0.05). The combination of CXCL17 density and immune infiltration could be used to further classify patients into subsets with different prognosis for RFS. Our results provide the first evidence that tumor-infiltrating CXCL17+ cell density is an independent prognostic factor that predicts both OS and RFS in HCC. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies.
| S-EPMC4193880 | biostudies-literature
Project description:Background: The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC). Methods: We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics. Results: NTF3 was low expressed in HCC and was an independent prognostic factor in patients with HCC. CIBERSORT analysis indicated that NTF3 expression was positively correlated with CD4+ cells, mast cells, NK cells, macrophages and B cells in the tumor microenvironment. Furthermore, we found that NTF3 expression was negatively correlated with the immune checkpoints PD-L1, TIGIT and TIM-3. Functional network analysis revealed that NTF3 regulates HCC progression through a variety of cancer-related kinases, transcription factors and signaling pathways. Conclusions: We demonstrate that NTF3 correlates with prognosis and immune infiltration in HCC.
| S-EPMC8685419 | biostudies-literature
Project description:BackgroundRecent evidence has shown that Solute Carrier Family 39 Member 10 (SLC39A10) promoted tumor progression in several cancer types. The study intended to explore the expression and function of SLC39A10 in hepatocellular carcinoma (HCC).MethodsMultiple bioinformatics analyses were used to evaluate SLC39A10 expression and potential role in HCC. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to confirm SLC39A10 expression. Intro studies were performed to assess the effects of SLC39A10 on HCC cells proliferation and migration. Furthermore, flow cytometry was conducted to identify its specific function in apoptosis of HCC.ResultsSLC39A10 was significantly over-expressed in HCC samples from both bioinformatic databases and our cohort. Survival analyses suggested patients with high expression of SLC39A10 had poor overall survival and disease-free survival (P-value <0.01). Further, the expression of SLC39A10 was positively correlated with tumor-infiltrating lymphocytes and some immune checkpoints like CTLA4, TIM3 and TGFB1. In HCC cell lines, SLC39A10 knockdown inhibited cells proliferation and migration, but promoted apoptosis.ConclusionAn increased SLC39A10 expression was found and served as an unfavorable indicator of survival in HCC. Further studies suggested SLC39A10 promotes tumor aggressiveness and may provide a novel target for HCC therapy.
| S-EPMC8357404 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that semaphorin 3F (SEMA3F) plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of SEMA3F in HCC remains not fully determined. In this study, we first performed pan-cancer analysis for SEMA3F's expression and prognosis using The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that SEMA3F might be a potential oncogene in HCC. Subsequently, noncoding RNAs (ncRNAs) contributing to SEMA3F overexpression were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the TMPO-AS1/SNHG16-let-7c-5p axis was identified as the most potential upstream ncRNA-related pathway of SEMA3F in HCC. Moreover, SEMA3F level was significantly positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncRNAs-mediated upregulation of SEMA3F correlated with poor prognosis and tumor immune infiltration in HCC.
| S-EPMC8121632 | biostudies-literature
Project description:ADAM15 is highly expressed in malignant tumors and is correlated with tumor progression. However, the role of ADAM15 in hepatocellular carcinoma (HCC) remains unclear. In the study, our results indicated that ADAM15 was highly expressed in HCC tissues and cells compared with corresponding tissues and liver cells. Overexpression of ADAM15 was linked to poor prognosis, and was an independent risk factor for HCC prognosis. Besides, analysis of immune infiltration indicated that ADAM15 expression was related to tumor infiltrating lymphocytes based on the TIMER, TISIDB and GEPIA databases. Many immune checkpoint gene expression was associated with ADAM15 expression. Functional enrichment analyses indicated that apoptosis, cell adhesion was enriched. ADAM15 knockdown promoted apoptosis and suppressed proliferation, migration and invasion of liver cancer cells. The findings of western blot showed that ADAM15 knockdown reduced the expression of Bcl-2, Vimentin, N-Cadherin and Snail, and elevated the expression of Bax, E-cadherin and ZO-1. However, overexpression of ADAM15 had the opposite results. Collectively, our findings demonstrated that ADAM15 was connected with poor prognosis of HCC patients, and could be considered as a potential biomarker for the diagnosis and treatment of HCC.
| S-EPMC8436918 | biostudies-literature
Project description:Objective: This study aimed to validate FANCI as a potential marker for both prognosis and therapy in liver hepatocellular carcinoma. Method: FANCI expression data were acquired from GEPIA, HPA, TCGA, and GEO databases. The impact of clinicopathological features was analyzed by UALCAN. The prognosis of Liver Hepatocellular Carcinoma (LIHC) patients with highly expressed FANCI was constructed utilizing Kaplan-Meier Plotter. GEO2R was employed to identify differentially expressed genes (DEGs). Metascape was used to analyze functional pathways correlations. Protein-Protein interaction (PPI) networks were generated by Cytoscape. Furthermore, molecular complex detection (MCODE) was utilized to recognize Hub genes, which were selected to establish a prognostic model. Lastly, the relationship between FANCI and immune cell infiltration in LIHC was examined. Results: Compared to adjacent tissues, FANCI expression levels were significantly higher in LIHC tissues and were positively correlated to the cancer grade, stage, and prior hepatitis B virus (HBV) infection. High expression of FANCI was found to be associated with poor prognosis in LIHC (HR=1.89, p<0.001). DEGs that were positively correlated with FANCI were involved in various processes, including the cell cycle, VEGF pathway, immune system processes, and biogenesis of ribonucleoproteins. MCM10, TPX2, PRC1, and KIF11 were identified as key genes closely related to FANCI and poor prognosis. A reliable five-variable prognostic model was constructed with strong predictive capability. Lastly, a positive correlation was observed between FANCI expression and tumor-infiltration levels of CD8+ T cells, B cells, regulatory T (Tregs), CD4+ T helper 2 (Th2), and macrophage M2 cells. Conclusion: FANCI may hold promise as a potential biomarker for predicting prognostic outcomes, and a valuable therapeutic target for LIHC patients, with a focus on anti-proliferation, anti-chemoresistance, and combination with immunotherapy.
| S-EPMC10266051 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is a primary liver cancer with high mortality worldwide. Even though the patients with HCC received standard therapies, patients with HCC continue to experience unsatisfactory therapy outcomes. Presently, immune therapy acts as a novel therapeutic management for HCC. The aim of this study was to determine overexpressed genes in HCC and evaluate the association between overexpressed genes with the prognosis and immune infiltration.MethodsGene expression profiles of HCC were analyzed using multiple online databases, and then confirmed by qualitative real time-polymerase chain reaction (RT-qPCR) and immunohistochemical analysis. The correlations of gene overexpression with the prognosis and immune infiltration were determined.ResultsTop 11 common differentially expressed genes were identified in HCC, and RACGAP1 was selected for further analysis. RACGAP1 expression was significantly higher in HCC tissues than that in normal tissues. Upregulation of RACGAP1 was correlated with clinical stage and poor prognosis. Additionally, RACGAP1 overexpression was positively related to the infiltration of suppressive immune cells. Moreover, we speculate RACGAP1 may promote tumorigenesis of HCC through immunosuppression mediated by YAP activation.ConclusionsOverexpression of RACGAP1 was associated with unfavorable prognosis and immune infiltration in HCC, which indicated that RACGAP1 could be a molecular target for HCC.
| S-EPMC10928639 | biostudies-literature
Project description: Not available
| S-EPMC11208630 | biostudies-literature
Project description:BackgroundThe protein kinesin family member 26B (KIF26B) is aberrantly expressed in various cancers. However, its particular role and association with tumor immune infiltration in colon adenocarcinoma (COAD) remain unclear.MethodsAll original data were downloaded directly from The Cancer Genome Atlas (TCGA), UCSC Xena, and Gene Expression Omnibus (GEO) databases and processed with R 3.6.3. KIF26B expression was analyzed using Oncomine, TIMER, TCGA, GEO databases, and our clinical specimens. KIF26B expression at the protein level was explored with Human Protein Atlas (HPA) database. The upstream miRNAs and lncRNAs were predicted by StarBase and validated using RT-qPCR. Correlation of KIF26B expression with the expression of immune-related or immune checkpoint genes and GSEA analysis of KIF26B-related genes were investigated via R software. Relationship of KIF26B expression with immune biomarkers or tumor immune infiltration levels was studied through GEPIA2 and TIMER databases.ResultsKIF26B was upregulated, and its overexpression was closely related to overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), T stage, N stage, and CEA levels in COAD. MIR4435-2HG/hsa-miR-500a-3p/KIF26B axis was identified as the promising regulatory pathway of KIF26B. KIF26B expression was positively correlated with immune-related genes, tumor immune infiltration, and biomarker genes of immune cells in COAD, and KIF26B-related genes were significantly enriched in macrophage activation-related pathways. Expression of immune checkpoint genes, including PDCD1, CD274, and CTLA4, was also closely related to KIF26B expression.ConclusionsOur results clarified that ncRNA-based increased KIF26B expression was associated with a worse prognosis and high tumor immune infiltration in COAD.
| S-EPMC10446804 | biostudies-literature