Comprehensive pan-cancer analysis of HSPG2 as a marker for prognosis

Our plain-English summary of Comprehensive pan-cancer analysis of HSPG2 as a marker for prognosis, by F. Chen, X. Gu, G. Qiang (BMC Medical Genomics, 2025).

The study

• Authors: F. Chen, X. Gu, G. Qiang
• Journal: BMC Medical Genomics
• Published: 2025;18(1):33
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: In recent years, several studies have shown that HSPG2 is associated with the prognosis of specific cancers. The aim of this study was to investigate the prognostic value of HSPG2 in pan-cancer and to analyze its possible mechanisms.

Methods: We used The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to explore the expression of HSPG2 in 33 tumors and corresponding controls. Univariate Cox regression and Kaplan-Meier survival analysis were applied to detect the effects of HSPG2 on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in patients with these tumors, and to analyze the relationship between HSPG2 and clinical characteristics. And we further analyzed the relationship between HSPG2 and immune infiltration, DNA methylation and single cell function. And GO and KEGG enrichment analyses were performed using HSPG2 co-expressed genes. Finally, we explored the diagnostic efficacy of HSPG2 for diseases of interest and validated it using qPCR experiment.

Results: HSPG2 was lowly expressed in 17 cancers and highly expressed in 11 cancers, and was correlated with patient's clinical characteristics in many cancers. Multivariate regression analysis showed that HSPG2 was an independent prognostic factor for DSS, OS, and PFI in bladder urothelial carcinoma (BLCA) and Mesothelioma (MESO). HSPG2 was correlated with DNA methylation, single-cell function, and immune infiltration in a variety of cancers. HSPG2 exhibited a good diagnostic efficacy for BLCA and MESO. qPCR and western blot results showed that HSPG2 expression was increased in mesothelioma compared to normal controls.

Conclusion: These findings suggest that HSPG2 could be considered as a potential diagnostic and prognostic marker for BLCA and MESO.

© 2025. The Author(s).

In plain English

This was a computer analysis of public cancer gene databases, plus cell experiments. It did not set out to study asbestos, which appeared only as one factor in the survival analysis. The authors measured HSPG2 gene activity across 33 tumor types; the gene makes perlecan. Compared with normal tissue, HSPG2 activity was lower in 17 cancers and higher in 11. Among 86 mesothelioma patients split at the median HSPG2 level, the high group had shorter overall survival after adjustment (hazard ratio 2.219, 95% confidence interval 1.347 to 3.656). Disease-specific survival and progression-free interval showed the same direction, and so did bladder urothelial carcinoma. Among 69 mesothelioma patients with a recorded asbestos history (55 exposed, 14 not), exposure was not significantly linked to their overall survival (hazard ratio 0.988, 0.520 to 1.879). In a separate dataset, HSPG2 distinguished mesothelioma from comparison samples with an area under the curve of 0.777 (0.683 to 0.872). One mesothelioma cell line had higher HSPG2 than one normal mesothelial line. The authors concluded HSPG2 could be considered a potential diagnostic and prognostic marker for bladder urothelial carcinoma and mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatics analysis of public cancer databases (TCGA, GTEx, GEO and other online tools), with qPCR and western blot experiments in cell lines
• Who was studied: Tumor and normal tissue data for 33 cancer types from public databases. The mesothelioma survival analysis included 86 patients for overall survival (43 high, 43 low HSPG2). A GEO mesothelioma dataset (GSE51024: 55 tumor samples, 41 paired samples) was also used, as was one mesothelioma cell line (NCI-H2452) compared with one normal mesothelial cell line (MET-5A).
• Exposure: The factor studied was the expression level of the HSPG2 gene (perlecan), with patients split at the median into high and low groups. Asbestos was not the main exposure under study. 'History asbestos exposure' appeared only as one variable in the mesothelioma survival table. No fiber types were named.
• Main results:
  • Compared with normal tissue, HSPG2 was expressed at lower levels in 17 cancers and higher levels in 11 cancers. Mesothelioma was not in either list, because the databases lacked mesothelioma controls.
  • Mesothelioma, multivariate analysis, overall survival: high versus low HSPG2 hazard ratio 2.219 (95% CI 1.347 to 3.656), p = 0.002 (86 patients)
  • Mesothelioma, multivariate analysis, disease-specific survival: high versus low HSPG2 hazard ratio 3.056 (95% CI 1.597 to 5.849), p less than 0.001 (66 patients). The univariate figure printed is identical.
  • Mesothelioma, multivariate analysis, progression-free interval: high versus low HSPG2 hazard ratio 2.264 (95% CI 1.279 to 4.010), p = 0.005 (84 patients)
  • Bladder urothelial carcinoma, multivariate analysis, overall survival: high versus low HSPG2 hazard ratio 2.204 (95% CI 1.055 to 4.604), p = 0.036. Results for disease-specific survival and progression-free interval were also above 1 and statistically significant.
  • In the mesothelioma survival table, 69 patients had a recorded asbestos exposure history (55 yes, 14 no). Among these already-diagnosed patients, exposure history was not statistically significantly associated with overall survival in univariate analysis: hazard ratio 0.988 (95% CI 0.520 to 1.879), p = 0.972. This concerns survival, not the risk of developing mesothelioma.
  • Area under the curve for HSPG2 in diagnosis was 0.650 (0.572 to 0.727) for bladder urothelial carcinoma and 0.777 (0.683 to 0.872) for mesothelioma, within the analyzed datasets
  • In the GEO dataset, HSPG2 expression in mesothelioma differed from the control group (adjusted p = 1.17e-4)
  • In cell experiments, qPCR showed higher HSPG2 in the mesothelioma cell line than in the normal mesothelial cell line (p less than 0.001). Western blot also showed more HSPG2 protein.
• The authors' conclusion: The authors concluded that HSPG2 could be considered a potential diagnostic and prognostic marker for bladder urothelial carcinoma and mesothelioma.
• Limitations the authors state:
  • All analyses were based on bioinformatics, and HSPG2 expression was confirmed by qPCR in only some tumors
  • The study did not investigate the molecular mechanism of HSPG2 in cancer
  • Splitting patients at the median HSPG2 level may have caused some real differences to appear negative

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Overall Survival, Carcinoma, Mesothelioma.

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