Dataset Information

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

ABSTRACT:

Background

Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined.

Methods

The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan-Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods.

Results

NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis.

Conclusions

NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

SUBMITTER: Ning YM

PROVIDER: S-EPMC9392949 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

Ning Yu-Mei YM Lin Kun K Liu Xiao-Ping XP Ding Yang Y Jiang Xiang X Zhang Zhang Z Xuan Yu-Ting YT Dong Li L Liu Lan L Wang Fan F Zhao Qiu Q Wang Hai-Zhou HZ Fang Jun J

BMC gastroenterology 20220820 1

<h4>Background</h4>Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined.<h4>Methods</h4>The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan coho ...[more]

PMID: 35987606

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Project description:IntroductionTumor purity takes on critical significance to the progression of solid tumors. The aim of this study was at exploring potential prognostic genes correlated with tumor purity in hepatocellular carcinoma (HCC) by bioinformatics analysis.MethodsThe ESTIMATE algorithm was applied for determining the tumor purity of HCC samples from The Cancer Genome Atlas (TCGA). The tumor purity-associated genes with differential expression (DEGs) were identified based on overlap analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis. The prognostic genes were identified in terms of the prognostic model construction based on the Kaplan-Meier (K-M) survival analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses. The expression of the above-described genes was further validated by the GSE105130 dataset from the Gene Expression Omnibus (GEO) database. We also characterized the clinical and immunophenotypes of prognostic genes. Gene set enrichment analysis (GSEA) was carried out for exploring the biological signaling pathway.ResultsA total of 26 tumor purity-associated DEGs were identified, which were involved in biological processes such as immune/inflammatory responses and fatty acid elongation. Ultimately, we identified ADCK3, HK3, and PPT1 as the prognostic genes for HCC. Moreover, HCC patients exhibiting higher ADCK3 expression and lower HK3 and PPT1 expressions had a better prognosis. Furthermore, high HK3 and PPT1 expressions and low ADCK3 expression resulted in high tumor purity, high immune score, high stromal score, and high ESTIMATE score. GSEA showed that the abovementioned prognostic genes showed a significant correlation with immune-inflammatory response, tumor growth, and fatty acid production/degradation.DiscussionIn conclusion, this study identified novel predictive biomarkers (ADCK3, HK3, and PPT1) and studied the underlying molecular mechanisms of HCC pathology initially.

Project description:Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients. HCC patients with low MAPK10 expression have lower expression scores of tumor infiltration lymphocytes (TILs) and stromal cells in the TME and increased scores of tumor cells than those with high MAPK10 expression. Further transcriptomic analyses revealed that the immune activity in the TME of HCC was markedly reduced in the low-MAPK10 group of HCC patients compared to the high-MAPK10 group. Additionally, we identified 495 differentially expressed immune-associated genes (DIGs), with 482 genes down-regulated and 13 genes up-regulated in parallel with the decrease of MAPK10 expression. GO enrichment and KEGG pathway analyses indicated that the biological functions of these DIGs included cell chemotaxis, leukocyte migration and positive regulation of the response to cytokine-cytokine receptor interaction, T cell receptor activation and MAPK signaling pathway. Protein-protein interaction (PPI) analyses of the 495 DIGs revealed five potential downstream hub genes of MAPK10, including SYK, CBL, VAV1, LCK, and CD3G. Several hub genes such as SYK, LCK, and VAV1 could respond to the immunological costimulatory signaling mediated by the transmembrane protein ICAM1, which was identified as a down-regulated DIG associated with low-MAPK10 expression. Moreover, ectopic overexpression or knock-down of MAPK10 could up-regulate or down-regulate ICAM1 expression via phosphorylation of c-jun at Ser63 in HCC cell lines, respectively. Collectively, our results demonstrated that MAPK10 down-regulation likely contributes to the immunosuppressive TME of HCC, and this gene might serve as a potential immunotherapeutic target and a prognostic factor for HCC patients.

Project description:Background Copper (Cu) metabolism is strongly associated with liver disease. Cuproptosis is a novel format of cell death, and cuproptosis-related genes (CRGs) were identified. However, the role of CRGs in Hepatocellular Carcinoma (HCC) remains unknown. Method The mRNA transcriptome profiling data, somatic mutation data, and copy number gene level data of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma project (TCGA-LIHC) were downloaded for subsequent analysis. Molecular characterization analysis of CRGs, including differential gene expression analysis, mutation analysis, copy number variation (CNV) analysis, Kaplan-Meier analysis, and immune regulator prioritization analysis, was implemented. The nonnegative matrix factorization (NMF) approach was used to identify the CRG-related molecular subtypes. Principal component analysis was adopted to verify the robustness and reliability of the molecular subtype. The least absolute shrinkage and selection operator regression analysis was performed to construct the prognostic signature based on differentially expressed genes between molecular subtypes. The survival characteristics of the molecular subtype and the signature were analyzed. The Gene Set Variation Analysis was performed for functional annotation. The immune landscape analysis, including immune checkpoint gene analysis, single sample gene set enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, immune infiltration cell, and tumor mutation burden analysis (TMB), was conducted. The ability of the signature to predict conventional anti-HCC agent responses was evaluated. The signature was validated in the LIRI-JP cohort and the IMvigor210 cohort. Result A total of 13 CRGs are differentially expressed between the tumor and normal samples, while the mutation of CRGs in HCC is infrequent. The expression of CRGs is associated with the CNV level. Fourteen CRGs are associated with the prognosis of HCC. Two clusters were identified and HCC patients were divided into 2 groups with a cutoff risk score value of 1.570. HCC patients in the C1 cluster and high-risk have a worse prognosis. The area under the receiver operating characteristic curve for predicting 1-, 2-, and 3-year overall survival is 0.775, 0.768, and 0.757 in the TCGA-LIHC cohort, and 0.811, 0.741, and 0.775 in the LIRI-JP cohort. Multivariate Cox regression analysis indicates that the signature is an independent prognostic factor. Pathways involved in metabolism and gene stability and immune infiltration cells are significantly enriched. Immune checkpoint genes are highly expressed in the C1 cluster. TMB is positively correlated with the risk score. HCC patients in the high-risk group are more likely to benefit from conventional anti-HCC agents and immune checkpoint inhibitor therapies. Conclusion The molecular characterization of CRGs in HCC is presented in this study, and a successful prognostic signature for HCC based on the cuproptosis-related molecular subtype was constructed.

Dataset Information

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

Similar Datasets

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