A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells

Wang, Youpeng; Yang, Yeni; Zhao, Zhi‐Wen; Sun, Hongfa; Luo, Dingan; Huttad, Lakshmi; Zhang, Bingyuan; Han, Bing

doi:10.1186/s12885-022-09465-9

Cited by 7 publications

(8 citation statements)

References 71 publications

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“…found that SPP1 expression was tightly linked to the TME reprogramming and tumor progression in response to therapy by single-cell transcriptomic analysis ( 67 ). S100A9, PLXNA1, and EPO were also reported as candidates for HCC prognostic signatures, implying their subtle effects on the disease progression of HCC patients ( 68 – 70 ). Moreover, BIRC5 was also found to be highly expressed in liver cancer ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Guo

Tang²,

Zhao³

et al. 2022

Front. Immunol.

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Hepatocellular carcinoma (HCC), accounting for ~90% of all primary liver cancer, is a prevalent malignancy worldwide. The intratumor heterogeneity of its causative etiology, histology, molecular landscape, and immune phenotype makes it difficult to precisely recognize individuals with high mortality risk or tumor-intrinsic treatment resistance, especially immunotherapy. Herein, we comprehensively evaluated the activities of cancer hallmark gene sets and their correlations with the prognosis of HCC patients using gene set variation analysis (GSVA) and identified two HCC subtypes with distinct prognostic outcomes. Based on these subtypes, seven immune-related genes (TMPRSS6, SPP1, S100A9, EPO, BIRC5, PLXNA1, and CDK4) were used to construct a novel prognostic gene signature [hallmark-guided subtypes-based immunologic signature (HGSIS)] via multiple statistical approaches. The HGSIS-integrated nomogram suggested an enhanced predictive performance. Interestingly, oncogenic hallmark pathways were significantly enriched in the high-risk group and positively associated with the risk score. Distinct mutational landscapes and immune profiles were observed between different risk groups. Moreover, immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) analysis showed different sensitivities of HGSIS risk groups for immune therapy efficacy, and the pRRophetic algorithm indicated distinguishable responses for targeted/chemotherapies in different groups. KIF2C was picked out as the key target concerning HGSIS, and the top 10 small molecules were predicted to bind to the active site of KIF2C via molecular docking, which might be further used for candidate drug discovery of HCC. Taken together, our study offers novel insights for clinically significant subtype recognition, and the proposed signature may be a helpful guide for clinicians to improve the treatment regimens.

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Section: Discussionmentioning

confidence: 99%

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Guo

Tang²,

Zhao³

et al. 2022

Front. Immunol.

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“…Previous studies have reported that inflammation-associated genes risk signature can be used to predict patient prognosis and guide treatment for esophageal squamous cell carcinoma, lung adenocarcinoma and urothelial bladder cancer. [28][29][30][31] Other hand, Sia et al determined that inflammation response-related gene signature could be correlated with the immune exhausted. 32 Many cancers are characterized by simultaneous immunosuppression and inflammation, their regulation is integrally linked, which can induce a dysfunctional immune state unable to eliminate disease.…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC

Lu¹,

Du²,

Feng³

et al. 2022

JIR

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Background Tumor growth depends on tumor cells and the tumor microenvironment, which are regulated by inflammation and immune responses. However, the roles of inflammation and immune status in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to evaluate the prognostic value of an inflammatory response- related gene signature associated with immune status, which may provide insight into new treatment options for HCC patients. Materials and Methods Differentially expressed genes associated with inflammation were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus, and the Molecular Signatures Database. An inflammation-associated prognostic gene signature was constructed and validated using TCGA and the International Cancer Genome Consortium datasets, respectively, using LASSO Cox regression analysis. Log-rank was performed to compare the overall survival of low- and high-risk score cohorts. Immune cell infiltration and immune-related functions were analyzed using single-sample gene enrichment analysis. The structures of the drugs identified by the prognostic model were predicted using PubChem. The drugs sensitivity of bleomycin, simvastatin and zoledronate detected by CCK8 colorimetric assay. The mRNA levels of 7 genes in HCC after drug treatment analyzed via qRT-PCR. Results Inflammation-associated genes, including ITGA5, MEP1A, P2RX4, RIPK2, SLC7A1 and SRI, were identified and found to be associated with the prognosis of HCC. We further found that the high-risk patients experienced poor prognosis, which was observed to be an independent and significant risk factor for prognosis. Moreover, we observed elevated expression levels in multiple immune cell types and immune function. Lastly, we validated that bleomycin, simvastatin and zoledronate could regulate these genes in HCC. Conclusion The inflammatory-response-associated gene signature could predict the prognosis and the immunological status of HCC patients. Additionally, bleomycin, simvastatin and zoledronate may represent potential drug candidates that could inhibit these genes. This may constitute a new approach for the treatment of HCC.

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“…A total of 905,677 million cases were estimated to be first diagnosed with HCC, and this disease caused 830,180 deaths in 2020 globally, ranking for approximately 4.7% of newly diagnosed cancer cases and 8.3% of cancer-related deaths [ 2 ]. Characterized by a high rate of invasiveness, recurrence and metastasis, the prognosis of HCC is poor, and the 5-year overall survival (OS) is only approximately 30% [ 3 ]. Although some risk factors have been identified for HCC, including HBV infection and alcohol consumption, the molecular mechanism of HCC is far from being elucidated [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

et al. 2023

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Background Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed malignancy and the third leading cause of cancer death globally. T cells are significantly correlated with the progression, therapy and prognosis of cancer. Limited systematic studies regarding the role of T-cell-related markers in HCC have been performed. Methods T-cell markers were identified with single-cell RNA sequencing (scRNA-seq) data from the GEO database. A prognostic signature was developed with the LASSO algorithm in the TCGA cohort and verified in the GSE14520 cohort. Another three eligible immunotherapy datasets, GSE91061, PRJEB25780 and IMigor210, were used to verify the role of the risk score in the immunotherapy response. Results With 181 T-cell markers identified by scRNA-seq analysis, a 13 T-cell-related gene-based prognostic signature (TRPS) was developed for prognostic prediction, which divided HCC patients into high-risk and low-risk groups according to overall survival, with AUCs of 1 year, 3 years, and 5 years of 0.807, 0.752, and 0.708, respectively. TRPS had the highest C-index compared with the other 10 established prognostic signatures, suggesting a better performance of TRPS in predicting the prognosis of HCC. More importantly, the TRPS risk score was closely correlated with the TIDE score and immunophenoscore. The high-risk score patients had a higher percentage of SD/PD, and CR/PR occurred more frequently in patients with low TRPS-related risk scores in the IMigor210, PRJEB25780 and GSE91061 cohorts. We also constructed a nomogram based on the TRPS, which had high potential for clinical application. Conclusion Our study proposed a novel TRPS for HCC patients, and the TRPS could effectively indicate the prognosis of HCC. It also served as a predictor for immunotherapy.

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A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells

Cited by 7 publications

References 71 publications

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates

A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC

A T-cell-related signature for prognostic stratification and immunotherapy response in hepatocellular carcinoma based on transcriptomics and single-cell sequencing

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