ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma

J Clin Lab Anal. 2022 Feb;36(2):e24228. doi: 10.1002/jcla.24228. Epub 2022 Jan 7.

Abstract

Background: Integrin α5 (ITGA5) was involved in a variety of cancers. However, the role of ITGA5 in laryngeal squamous cell carcinoma (LSCC) remains unknown.

Methods: The expression of ITGA5 and the corresponding clinicopathological parameters of LSCC patients the TCGA database. Five datasets (GSE51985, GSE59102, GSE84957, GSE27020, and GSE65858) were downloaded from the GEO database as validation sets. Kaplan-Meier plotter, Cox regression analysis, and nomogram were performed to determine the prognostic value of ITGA5 in LSCC. GO, KEGG, and GSEA were used to explore the underlying biological functions of ITGA5 in LSCC. The algorithms ESTIMATE and CIBERSORT were adopted to evaluate the association between ITGA5 and the infiltration of the immune cells. The algorithm pRRophetic was used to estimate the response to chemotherapeutic drugs.

Results: The expression of ITGA5 was higher in the LSCC samples and linked to poor overall survival and recurrence-free survival. Further, the Cox regression analysis confirmed that high expression of ITGA5 was an independent unfavorable prognostic factor. The predictive performance of nomogram based on the expression of ITGA5 was accurate and practical. The functional enrichment analysis confirmed that ITGA5 was related to the construction of the components and structures of the extracellular matrix. Finally, patients with high ITGA5 expression were more likely to benefit from docetaxel and gemcitabine.

Conclusion: The expression of ITGA5 was elevated in the LSCC and was a predictor for prognosis and chemotherapeutic response in LSCC patients.

Keywords: ITGA5; chemotherapy; laryngeal squamous cell carcinoma; nomogram; prognosis.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Cohort Studies
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Docetaxel / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Integrins / metabolism*
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / mortality
  • Male
  • Middle Aged
  • Nomograms
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • ITGA5 protein, human
  • Integrins
  • Deoxycytidine
  • Docetaxel
  • Gemcitabine