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NPLOC4 constructs tumor immunosuppressive microenvironment in pan-cancer and hepatocellular carcinoma
Wanli Zhang1, Chengdong Liu1, Xiaohan Zhou2
1Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R., China.
Introduction:
NPLOC4 (nuclear protein localization 4 homolog) is mainly involved in DNA damage, cell cycle, and ubiquitination promotion. Nonetheless, the role of NPLOC4 in the tumor immune microenvironment (TIME) and its potential as a promising tumor therapeutic target remains unclear.
Methods:
Therefore, analyses of NPLOC4 mRNA and protein expression, RNA subcellular localization, and patient prognosis associated with NPLOC4 expression were conducted across multiple tumor types. Additionally, the correlations between NPLOC4 and immune cells, non-immune cells, and immune molecules within the tumor immune microenvironment (TIME) were investigated. These analyses utilized data from various public resources, including the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), The Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), TIMER2.0, KM-Plotter, The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), and Tumor Immune Single-cell Hub 2 (TISCH2). Subsequently, we utilized hepatocellular carcinoma (HCC) patients' cancer and adjacent tissues plus tumor cell lines to verify the differential RNA and protein expression of NPLOC4 via qRT-PCR and immunohistochemistry (IHC). Then, the relationship of NPLOC4 expression level with immune infiltration score, infiltration of effector immune cells, suppressive immune cells, and several vital immune checkpoints was analyzed in HCC immune microenvironment. Furthermore, the distribution of expression of NPLOC4 in various cells in the HCC microenvironment was determined through single-cell sequencing analysis.
Results:
We discovered that NPLOC4 was up-regulated in a variety of tumors and was correlated with poor prognosis. NPLOC4 not only had the potential as a tumor prognostic marker and therapeutic target but also was strongly linked to immune cells, immune checkpoints, and immune-related molecules and pathways in HCC immune microenvironment.
Conclusion:
In summary, NPLOC4 may serve as a promising target for immunotherapy.
Insights
Nuclear protein localization 4 homolog (NPLOC4) is upregulated in many tumors, correlating with poor prognosis. This study reveals NPLOC4 as a potential therapeutic target in the tumor immune microenvironment, particularly in hepatocellular carcinoma.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Nuclear protein localization 4 homolog (NPLOC4) is implicated in DNA damage, cell cycle regulation, and ubiquitination.
- The specific role of NPLOC4 within the tumor immune microenvironment (TIME) and its therapeutic potential remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression patterns of NPLOC4 across various tumor types.
- To evaluate the prognostic significance of NPLOC4 in cancer.
- To explore the association between NPLOC4 and immune components within the tumor immune microenvironment, with a focus on hepatocellular carcinoma (HCC).
Main Methods:
- Analysis of NPLOC4 mRNA and protein expression using public databases (GTEx, TCGA, CCLE, HPA, CPTAC, TIMER2.0, KM-Plotter, UALCAN, TISCH2).
- Validation of NPLOC4 expression in HCC tissues and cell lines via qRT-PCR and immunohistochemistry.
- Investigation of NPLOC4 correlations with immune cell infiltration, immune checkpoints, and immune-related molecules in HCC using bioinformatics and single-cell sequencing data.
Main Results:
- NPLOC4 expression is elevated in numerous tumor types and is associated with unfavorable patient prognoses.
- NPLOC4 demonstrates significant correlations with immune cells, immune checkpoints, and immune-related molecules within the HCC immune microenvironment.
- NPLOC4 shows potential as a prognostic biomarker and a therapeutic target in cancer.
Conclusions:
- NPLOC4 is upregulated in various cancers and linked to poor outcomes.
- NPLOC4 plays a role in the tumor immune microenvironment, especially in HCC.
- NPLOC4 emerges as a potential target for novel cancer immunotherapies.
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