# Bioinformatics Identification and Functional Analysis of Key Genes of Nucleotide Metabolism in Oral Squamous Cell Carcinoma

**Authors:** Feng Wei, Hong Fan

PMC · DOI: 10.3290/j.ohpd.c_2470 · Oral Health & Preventive Dentistry · 2026-02-24

## TL;DR

This study identifies key genes in nucleotide metabolism that could help diagnose and treat oral cancer.

## Contribution

The study identifies ADA, NT5E, and TYMS as novel potential biomarkers and therapeutic targets for OSCC.

## Key findings

- Three hub genes (ADA, NT5E, and TYMS) showed good diagnostic performance with AUC > 0.7.
- Immune infiltration analysis revealed increased cytotoxic lymphocytes, B lineage, and monocytic lineage in OSCC.
- Potential drugs like denileukin difitox ontak and streptozocin were predicted for OSCC treatment.

## Abstract

Oral squamous cell carcinoma (OSCC) is a typical hypoxic and metabolically heterogeneous adult invasive oral malignant tumour. Nucleotide metabolism-related genes (NMRGs) have been identified as therapeutic targets for various cancers. This study aims to analyse the characteristics of NMRGs in OSCC and identify potential biomarkers.

Based on the the Cancer Genome Atlas (TCGA) and GEO data, differentially expressed genes (DEGs) in OSCC were screened and intersected with NMRGs to obtain DE-NMRGs. Key genes were selected through the protein interaction (PPI) network combined with MCC and MCODE algorithms, and receiver operating characteristic (ROC) and survival curves were drawn. Genes with an area under the curve (AUC) > 0.7 and statistically significant differences were selected as hub genes. Further analysis of the immune infiltration characteristics, gene set enrichment analysis (GSEA) enrichment, potential drug effects of hub genes, and construction of the ceRNA network were conducted.

Three hub genes related to nucleotide metabolism (ADA, NT5E, and TYMS) were identified, showing good diagnostic performance (AUC > 0.7). Immune analysis showed that cytotoxic lymphocytes, B lineage, and monocytic lineage had increased infiltration in OSCC (P < 0.05). The ceRNA network showed that hsa-miR-30a-5p, hsa-miR-30b-5p interacted with NT5E, and hsa-miR-192-5p, hsa-miR-215-5p interacted with TYMS. Drug prediction suggested that denileukin difitox ontak, STREPTOZOCIN, and nitrogen mustard may be potential therapeutic drugs for OSCC.

ADA, NT5E and TYMS can serve as potential diagnostic markers and therapeutic targets for OSCC. The study has reference value for early diagnosis and the development of individualised treatment strategies.

## Linked entities

- **Genes:** ADA (adenosine deaminase) [NCBI Gene 100], NT5E (5'-nucleotidase ecto) [NCBI Gene 4907], TYMS (thymidylate synthetase) [NCBI Gene 7298]
- **Chemicals:** STREPTOZOCIN (PubChem CID 29327), nitrogen mustard (PubChem CID 4033)
- **Diseases:** oral squamous cell carcinoma (MONDO:0004958)

## Full-text entities

- **Genes:** MIR378E (microRNA 378e) [NCBI Gene 100616498] {aka mir-378e}, TYMS (thymidylate synthetase) [NCBI Gene 7298] {aka DKCD, HST422, TMS, TS}, MIR3139 (microRNA 3139) [NCBI Gene 100423017], FOXD2-AS1 (FOXD2 adjacent opposite strand RNA 1) [NCBI Gene 84793], NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, GMPR (guanosine monophosphate reductase) [NCBI Gene 2766] {aka GMPR 1, GMPR1, hGMPR-I}, NT5C1A (5'-nucleotidase, cytosolic IA) [NCBI Gene 84618] {aka CN-I, CN-IA, CN1, CN1A, CNI}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CMPK2 (cytidine/uridine monophosphate kinase 2) [NCBI Gene 129607] {aka IBGC10, NDK, TMPK2, TYKi, UMP-CMPK2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, PTCH2 (patched 2) [NCBI Gene 8643] {aka PTC2, SLC65B2}, DAPK2 (death associated protein kinase 2) [NCBI Gene 23604] {aka DRP-1, DRP1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8) [NCBI Gene 377841] {aka E-NTPDase, GLSR2492, NTPDase-8, UNQ2492}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, BRIP1 (BRCA1 interacting DNA helicase 1) [NCBI Gene 83990] {aka BACH1, FANCJ, OF}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MIR378G (microRNA 378g) [NCBI Gene 100616321], TCL1A (TCL1 family AKT coactivator A) [NCBI Gene 8115] {aka TCL1}, AMPD1 (adenosine monophosphate deaminase 1) [NCBI Gene 270] {aka MAD, MADA, MMDD}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, AK1 (adenylate kinase 1) [NCBI Gene 203] {aka ADK, Adk1, CNSHA3, HTL-S-58j}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP}, BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] {aka BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD}, IMPDH1 (inosine monophosphate dehydrogenase 1) [NCBI Gene 3614] {aka IMPD, IMPD1, IMPDH-I, LCA11, RP10, sWSS2608}, ADSS1 (adenylosuccinate synthase 1) [NCBI Gene 122622] {aka ADSSL1, MPD5}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}
- **Diseases:** head and neck cancer (MESH:D006258), Cancer (MESH:D009369), inflammatory (MESH:D007249), HNSCC (MESH:D000077195), oral cancer (MESH:D009062), NMRGs (MESH:C566309), hypoxic (MESH:D002534), acute myeloid leukaemia (MESH:D054218), chronic periodontitis (MESH:D055113), precancerous lesions (MESH:D011230), Viral infections (MESH:D014777), CRC (MESH:D015179), II (MESH:C537730), oral epithelial tumour (MESH:D009375), metastasis (MESH:D009362), oral developmental disorders (MESH:D002658), Fanconi anaemia (MESH:D000743)
- **Chemicals:** paclitaxel (MESH:D017239), inosine (MESH:D007288), platinum (MESH:D010984), adenosine (MESH:D000241), Oxaliplatin (MESH:D000077150), BAY-2402234 (MESH:C000718176), Nucleotide (MESH:D009711), arachidonic acid (MESH:D016718), pipobroman (MESH:D010885), STREPTOZOCIN (MESH:D013311), nitrogen mustard (MESH:D008466), 5-FU (MESH:D005472), methotrexate (MESH:D008727), alantolactone (MESH:C004363), XR-5944 (MESH:C434883), Carboplatin (MESH:D016190), Ontak (-), cisplatin (MESH:D002945), docetaxel (MESH:D000077143), ROS (MESH:D017382), alcohol (MESH:D000438), RH1 (MESH:C117776), purine (MESH:C030985), AMP (MESH:D000249)
- **Species:** Clostridioides difficile (species) [taxon 1496], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** OSCC-3 — Homo sapiens (Human), Buccal mucosa squamous cell carcinoma, Cancer cell line (CVCL_D859), GEO — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0271)

## Full text

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## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12951043/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12951043/full.md

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Source: https://tomesphere.com/paper/PMC12951043