Research Paper Volume 15, Issue 12 pp 5611—5649

Identifying the role of NUDCD1 in human tumors from clinical and molecular mechanisms: a study based on comprehensive bioinformatics and experimental validation

Bin Han1,2,3, *, , Jinsong He4, *, , Qing Chen1,3,4, , Min Yuan1,3, , Xi Zeng1,3, , Yuanting Li1,3, , Yan Zeng1,2, , Meibo He1,2,3, , Dan Feng1,2,3, #,&, , Daiyuan Ma1,5, #, ,

  • 1 GCP Center/Institute of Drug Clinical Trials, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
  • 2 Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
  • 3 Institute of Pharmacy, North Sichuan Medical College, Nanchong, China
  • 4 Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
  • 5 Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Received: April 21, 2023       Accepted: May 31, 2023       Published: June 19, 2023
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Copyright: © 2023 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


NUDCD1: NudC domain-containing 1; HPA: Human Protein Atlas; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; GTEx: Genotype-Tissue Expression; TIMER2: Tumor Immune Estimation Resource, Version 2; UALCAN: The University of ALabama at Birmingham CANcer data analysis Portal; GEPIA2: Gene Expression Profiling Interactive Analysis, Version 2; cBioPortal: cBio Cancer Genomics Portal; TISIDB: web portal for tumor and immune system interaction; CPTAC: Clinical Proteomic Tumor Analysis Consortium; CTD: Comparative Toxicogenomics Database; STRING: search tool for the retrieval of interacting genes/proteins; GSEA: gene set enrichment analysis; GSVA: gene set variation analysis; KM: Kaplan-Meier; DFI: disease-free interval; DSS: disease-specific survival; OS: overall survival; PFS: progression-free survival; GSCA: Gene Set Cancer Analysis; CTRP: Cancer Therapeutics Response Portal; GDSC: Genomics of Drug Sensitivity in Cancer; ENCODE: Encyclopedia of DNA Elements; EMT: epithelial mesenchymal transition; WT: wild type; SNV: Single Nucleotide Variation; CNV: Copy Number Variation; MSI: microsatellite instability; TMB: tumor mutation burden; STAD: Stomach adenocarcinoma; COAD: Colon adenocarcinoma; ESCA: Esophageal carcinoma; SEM: standard errors of the mean; FANTOM5: Function annotation of the mammalian genome 5; BLCA: Bladder urothelial carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangio carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; LIHC: Liver hepatocellular carcinoma); LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; READ: Rectum adenocarcinoma; DLBC: Lymphoid neoplasm diffuse large B-cell lymphoma; LAML: Acute myeloid leukemia; THYM: Thymoma; RCC: Renal cell carcinoma; UCEC: Uterine corpus endometrial carcinoma; CML: Chronic myelogenous leukemia; KICH: Kidney chromophobe; KIRP: Kidney renal papillary cell carcinoma; THCA: Thyroid carcinoma; LGG: Brain lower grade glioma; SARC: Sarcoma; PAAD: Pancreatic adenocarcinoma); UVM: Uveal melanoma; PPI: protein interaction; ACC: Adrenocortical carcinoma; SKCM: Skin Cutaneous Melanoma; ACLBI: clinical bioinformatics.