# Bioinformatics analysis of laryngeal squamous cell carcinoma based on the high infection rate of HPV in Northwest China

**Authors:** Fan Guo, Shurong Li, Shiqi Yan, Yuqiao Zhang, Guangke Wang, Ruixia Ma

PMC · DOI: 10.7717/peerj.19851 · PeerJ · 2025-08-11

## TL;DR

This study explores how HPV affects laryngeal cancer in Northwest China, identifying key genes and pathways that could help in diagnosis and treatment.

## Contribution

The study identifies novel key genes and pathways specific to HPV-positive laryngeal cancer in a high-prevalence region.

## Key findings

- HPV infection rate in laryngeal cancer patients in Northwest China is 55.65%, with HPV16 being the most common genotype.
- Ten key genes and several pathways were found to be significantly involved in HPV-positive laryngeal cancer development.
- PXN, ITGB1, ISG15, SLC2A1, and ICAM1 are potential therapeutic targets for HPV-positive laryngeal cancer.

## Abstract

An increasing number of studies have demonstrated that human papillomavirus (HPV) plays a crucial role in the occurrence and development of laryngeal cancer. The present study aims to identify the differentially expressed genes and pathways in HPV-positive and HPV-negative laryngeal squamous cell carcinoma (LSCC) cells for the diagnosis and treatment of HPV-related LSCC, and to determine the prevalence rate of HPV in laryngeal cancer in Northwest China.

PCR-reverse dot blot was used to detect HPV genotypes in 115 LSCC patients’ paraffin sections from Jan 2022 to Jun 2024.HPV-positive TU212 cells (TU212HPV) were constructed via lentiviral transfection. RT-qPCR and Western blot detected mRNA and protein levels. RNA-seq and TMT sequenced gene and protein differences. DAVID database was used for Gene Ontology and pathway enrichment analyses. STRING and Cytoscape screened key genes and further analyzed pathways.

Among 115 patients, 64 were HPV-positive (HPV16 being the most common, 57 cases). The TU212HPV cell line was successfully constructed. RNA-seq identified 1,336 differentially expressed genes (797 upregulated, 539 downregulated). TMT found 236 differentially expressed proteins (124 upregulated, 112 downregulated). The key genes were discovered to be EGFR, CDC42, PXN, SLC2A1, GAPDH, FGF2, ICAM1, ITGB1, SFN, PGK1, and ISG15. Pathway enrichment showed involvement in neuroactive ligand-receptor interaction, Cytoskeleton in muscle cell, transcriptional misregulation in cancer, etc. (P < 0.05).

HPV infection rate is 55.65% among laryngeal cancer patients in Northwest China. Ten key genes, namely EGFR, CDC42, PXN, SLC2A1, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), FGF2, ICAM1, ITGB1, PGK1 and ISG15, as well as pathways like proteoglycans in cancer, regulation of actin cytoskeleton and HIF-1 signaling pathway are demonstrated to be of significance in the occurrence and development of laryngeal squamous cell carcinoma. PXN, ITGB1, ISG15, SLC2A1 and ICAM1 are regarded as potential therapeutic targets for HPV-positive laryngeal cancer. PXN and PGK1 are considered as potential prognostic markers for HPV-positive laryngeal cancer.

## Linked entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956], CDC42 (cell division cycle 42) [NCBI Gene 998], PXN (paxillin) [NCBI Gene 5829], SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513], GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597], FGF2 (fibroblast growth factor 2) [NCBI Gene 2247], ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383], ITGB1 (integrin subunit beta 1) [NCBI Gene 3688], PGK1 (phosphoglycerate kinase 1) [NCBI Gene 5230], ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636]
- **Diseases:** laryngeal cancer (MONDO:0002358), laryngeal squamous cell carcinoma (MONDO:0005595)

## Full-text entities

- **Genes:** ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, REXO2 (RNA exonuclease 2) [NCBI Gene 25996] {aka CGI-114, REX2, RFN, SFN}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, PGK1 (phosphoglycerate kinase 1) [NCBI Gene 5230] {aka HEL-S-68p, MIG10, PGKA}, CDC42 (cell division cycle 42) [NCBI Gene 998] {aka CDC42Hs, G25K, TKS}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, PXN (paxillin) [NCBI Gene 5829]
- **Diseases:** LSCC (MESH:D000077195), cancer (MESH:D009369), laryngeal cancer (MESH:D007822)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human papillomavirus 16 (serotype) [taxon 333760], Human papillomavirus (species) [taxon 10566]
- **Cell lines:** TU212 — Homo sapiens (Human), Head and neck squamous cell carcinoma, Cancer cell line (CVCL_4915)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12352419/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12352419/full.md

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Source: https://tomesphere.com/paper/PMC12352419