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Identifying the role of NUDCD1 in human tumors from clinical and molecular mechanisms: a study based on comprehensive
Bin Han1,2,3, Jinsong He4, Qing Chen1,3,4
1GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Abstract:
NUDCD1 (NudC domain-containing 1) is abnormally activated in multiple tumors and has been identified as a cancer antigen. But there is still no pan-cancer analysis available for NUDCD1 in human cancers. The role of NUDCD1 across multiple tumors was explored using data from the public databases including HPA, TCGA, GEO, GTEx, TIMER2, TISIDB, UALCAN, GEPIA2, cBioPortal, GSCA and so on. Molecular experiments (e.g., quantitative real-time PCR, immunohistochemistry and western blot) were conducted to validate the expression and biological function of NUDCD1 in STAD. Results showed that NUDCD1 was highly expressed in most tumors and its levels were associated with the prognosis. Multiple genetic and epigenetic features of NUDCD1 exist in different cancers. NUDCD1 was associated with expression levels of recognized immune checkpoints (anti-CTLA-4) and immune infiltrates (e.g., CD4+ and CD8+ T cells) in some cancers. Moreover, NUDCD1 correlated with the CTRP and GDSC drug sensitivity and acted as a link between chemicals and cancers. Importantly, NUDCD1-related genes were enriched in several tumors (e.g., COAD, STAD and ESCA) and affected apoptosis, cell cycle and DNA damage cancer-related pathways. Furthermore, expression, mutation and copy number variations for the gene sets were also associated with prognosis. At last, the overexpression and contribution of NUDCD1 in STAD were experimentally validated in vitro and in vivo. NUDCD1 was involved in diverse biological processes and it influenced the occurrence and development of cancers. This first pan-cancer analysis for NUDCD1 provides a comprehensive understanding about its roles across various cancer types, especially in STAD.
Insights
NudC domain-containing 1 (NUDCD1) is highly expressed in most cancers and linked to poor prognosis. This study provides the first pan-cancer analysis of NUDCD1, revealing its role in immune response, drug sensitivity, and cancer pathways, particularly in stomach adenocarcinoma (STAD).
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- NudC domain-containing 1 (NUDCD1) is an identified cancer antigen with abnormal activation in multiple tumors.
- A comprehensive pan-cancer analysis of NUDCD1's role across human cancers is currently lacking.
Purpose of the Study:
- To conduct the first pan-cancer analysis of NUDCD1 expression, genetic alterations, and clinical significance in human cancers.
- To investigate the association of NUDCD1 with immune infiltration, drug sensitivity, and cancer-related pathways.
- To experimentally validate the function of NUDCD1 in stomach adenocarcinoma (STAD).
Main Methods:
- Utilized public databases (HPA, TCGA, GEO, GTEx, TIMER2, TISIDB, UALCAN, GEPIA2, cBioPortal, GSCA) for pan-cancer analysis.
- Performed molecular experiments including quantitative real-time PCR, immunohistochemistry, and western blot for STAD validation.
- Analyzed NUDCD1 expression, genetic/epigenetic features, immune cell infiltration, drug sensitivity, and pathway enrichment.
Main Results:
- NUDCD1 is highly expressed in most tumors and associated with poorer prognosis.
- Found significant correlations between NUDCD1 and immune checkpoints (e.g., anti-CTLA-4) and immune infiltrates (CD4+, CD8+ T cells).
- NUDCD1 demonstrated links to drug sensitivity and was involved in key cancer pathways like apoptosis, cell cycle, and DNA damage, with experimental validation in STAD.
Conclusions:
- NUDCD1 plays a significant role across various cancers, influencing tumor development, immune evasion, and therapeutic response.
- This pan-cancer analysis establishes NUDCD1 as a potential pan-cancer biomarker and therapeutic target, especially in STAD.
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