HSPA5 is a prognostic biomarker correlated with immune infiltrates in thyroid carcinoma

Endokrynol Pol. 2022;73(4):680-689. doi: 10.5603/EP.a2022.0045.

Abstract

Introduction: Thyroid carcinoma (THCA) is the most common endocrine malignancy. Recent research has shown heat shock protein family A (HSPA5) as a diagnostic and prognostic biomarker for various malignancies. Nevertheless, the role of HSPA5 in THCA is unclear. This study aims to explore HSPA5 expression in THCA and its potential diagnostic and therapeutic value for THCA.

Material and methods: We obtained the data of HSPA5 expression in THCA and normal thyroid tissues from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). We used the Shapiro-Wilk normality test, Levene's test, t-test, Dunn's test, Kruskal-Wallis test, Wilcoxon rank sum test, chi-square test, Fisher's exact test, and logistic regression to evaluate the relationship between the expression of HSPA5 and clinicopathological features. Kaplan-Meier method and Cox regression were applied to analyse the correlation between the expression level of HSPA5 and prognosis of THCA patients, and to construct a prognosis prediction model of THCA patients. Gene set enrichment analysis (GSEA) was applied to explore the potential pathway related to HSPA5 in THCA.

Results: HSPA5 expression was lower in THCA tissues than in normal thyroid tissues (p < 0.001). Low expression of HSPA5 in THCA patients was related to poorer T stage (p < 0.001), N stage (p < 0.001), pathologic stage (p < 0.001), tumour extrathyroidal extension (p < 0.001), residual tumour (p = 0.03), and progression-free interval (PFI) event (p = 0.002). Low HSPA5 expression was associated with poor PFI. According to the results of univariate analysis, THCA patients who had high HSPA5 levels had longer PFI (p = 0.042). Enrichment analysis via GO/KEGG showed that the top 10 genes related to HSPA5 were all enriched in the pathways related to endoplasmic reticulum function. Moreover, HSPA5 expression was related to immune infiltrating cells.

Conclusions: Decreased expression of HSPA5 is associated with worse clinicopathological features, shorter PFI and higher immune infiltration level of multiple immune cells, which demonstrated that HSPA5 is a prognostic biomarker in THCA.

Keywords: HSPA5; bioinformatics analysis; endoplasmic reticulum protein; immune cell infiltration; prognosis; thyroid carcinoma.

MeSH terms

  • Biomarkers
  • Humans
  • Prognosis
  • Thyroid Neoplasms* / genetics

Substances

  • Biomarkers