Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy

Zhang, Yanpeng; Zhaorigetu, Bao; Wu, Jingbang; Chen, Yunhao; Chen, Jun‐Ru; Xie, Haiyang; Zhou, Lin; Wu, Jian; Zheng, Shusen

doi:10.1177/1533033820944274

Cited by 6 publications

(5 citation statements)

References 60 publications

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“…The expression levels of CDK1 and CCNB2 are correlated with the immune in ltration of CD8 T cells in hepatocellular carcinoma and indicate a worse prognosis [29]. BUB1B was reported to contribute to the resistance of CD8+ T-cell in ltration in hepatocellular carcinoma [30].…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Bao

Sun²,

Zhang

2022

Preprint

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Background: The immune microenvironment of lung cancer is complex, and T-cell tolerance is a primary mechanism of immune evasion. Tumor-derived exosomes (TEX) miRNAs regulate immune cells in tumor microenvironment (TME), contributing to tumor immune suppression. However, the underlying mechanisms remain unclear.Methods: TEX miRNA expression dataset (GSE111803) and CD8+ T cells mRNA expression profile (GSE90728) in lung adenocarcinoma (LUAD) were downloaded from Gene Expression Omnibus (GEO). The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were analyzed. The intersection of target genes of DEMs and DEGs was defined as the overlapped target genes. We performed the function and pathway analysis for DEGs and the overlapped genes by the DAVID tool and constructed a protein-protein interaction (PPI) network to screen modules and hub genes. Results: In total, 7 DEMs (5 upregulated and two downregulated miRNAs) and 672 DEGs (219 upregulated and 453 downregulated genes) were identified, then 185 overlapped genes for upregulated DEMs were selected for further analysis. GO analysis indicated the DEGs were mainly enriched in positive regulation of B cell activation, innate immune, while the overlapped genes were primarily involved in regulation of immune response. The pathway analysis suggested DEGs were primarily enriched in cytokine-cytokine receptor interaction, while the overlapped genes were primarily enriched in osteoclast differentiation. The PPI network revealed three significant modules for DEGs and the overlapped genes sets. These modules genes were mainly enriched in cell cycle, chemokine signaling pathway, and cytokine-cytokine receptor interaction, respectively.Conclusions: These results preliminarily revealed the mRNA expression profiles and the molecular regulatory mechanism of TEX miRNA regulated tumor immune response in LUAD.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Bao

Sun²,

Zhang

2022

Preprint

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“…As far as we are aware, the present study is the most comprehensive investigation of CTA-expression in tumor and paired TFL tissues of HCC-patients performed. Another recent report used the GEPIA database to analyze CTA expression in tumors of HCC patients, but did not investigate CTA expression in non-cancerous liver tissues of HCC patients [20]. An additional benefit of excluding CTAs expressed in healthy tissues would be their suitability for therapeutic targeting, as targeting proteins exclusively expressed in the tumor will not lead to therapy-induced auto-immunity in potential future clinical applications [8].…”

Section: Discussionmentioning

confidence: 99%

Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Noordam

Ozturk

et al. 2021

Cancers

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High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

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“…A series of CT genes are upregulated in hepatocellular carcinoma, involved in cellcycle regulation, cancer progression, and signaling pathways and can serve as biomarkers for diagnostics, prognostics, and treatment [55,56].…”

Section: Differential Expression Of Cancer-testis-specific Genesmentioning

confidence: 99%

Comparative RNA-Sequencing Analysis Reveals High Complexity and Heterogeneity of Transcriptomic and Immune Profiles in Hepatocellular Carcinoma Tumors of Viral (HBV, HCV) and Non-Viral Etiology

et al. 2022

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Background and Objectives: Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is the leading cause of cancer-related mortality. It arises and progresses against fibrotic or cirrhotic backgrounds mainly due to infection with hepatitis viruses B (HBV) or C (HCV) or non-viral causes that lead to chronic inflammation and genomic changes. A better understanding of molecular and immune mechanisms in HCC subtypes is needed. Materials and Methods: To identify transcriptional changes in primary HCC tumors with or without hepatitis viral etiology, we analyzed the transcriptomes of 24 patients by next-generation sequencing. Results: We identified common and unique differentially expressed genes for each etiological tumor group and analyzed the expression of SLC, ATP binding cassette, cytochrome 450, cancer testis, and heat shock protein genes. Metascape functional enrichment analysis showed mainly upregulated cell-cycle pathways in HBV and HCV and upregulated cell response to stress in non-viral infection. GeneWalk analysis identified regulator, hub, and moonlighting genes and highlighted CCNB1, ACTN2, BRCA1, IGF1, CDK1, AURKA, AURKB, and TOP2A in the HCV group and HSF1, HSPA1A, HSP90AA1, HSPB1, HSPA5, PTK2, and AURKB in the group without viral infection as hub genes. Immune infiltrate analysis showed that T cell, cytotoxic, and natural killer cell markers were significantly more highly expressed in HCV than in non-viral tumors. Genes associated with monocyte activation had the highest expression levels in HBV, while high expression of genes involved in primary adaptive immune response and complement receptor activity characterized tumors without viral infection. Conclusions: Our comprehensive study underlines the high degree of complexity of immune profiles in the analyzed groups, which adds to the heterogeneous HCC genomic landscape. The biomarkers identified in each HCC group might serve as therapeutic targets.

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Cancer-Testis Gene Expression in Hepatocellular Carcinoma: Identification of Prognostic Markers and Potential Targets for Immunotherapy

Cited by 6 publications

References 60 publications

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Comparative RNA-Sequencing Analysis Reveals High Complexity and Heterogeneity of Transcriptomic and Immune Profiles in Hepatocellular Carcinoma Tumors of Viral (HBV, HCV) and Non-Viral Etiology

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