Divergent roles of PRR11 and HEPACAM in pleural mesothelioma: PRR11 as a prognostic biomarker and HEPACAM as a stage-associated gene with paradoxical expression

Our plain-English summary of Divergent roles of PRR11 and HEPACAM in pleural mesothelioma: PRR11 as a prognostic biomarker and HEPACAM as a stage-associated gene with paradoxical expression, by R.X. Zhao, M.L. Zhang, Q. Wang, et al (Translational Cancer Research, 2026).

The study

• Authors: R.X. Zhao, M.L. Zhang, Q. Wang, K.H. Lu
• Journal: Translational Cancer Research
• Published: 2026;15(6):476
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. While identifying drivers of tumor progression is critical, the molecular alterations specifically associated with T-stage advancement remain poorly understood. This study aimed to investigate genes linked to T-stage progression in PM using The Cancer Genome Atlas (TCGA) data, with a focus on the previously unreported roles of PRR11 and HEPACAM in this disease.

Methods: RNA-sequencing data and clinical information for 87 PM patients were obtained from the TCGA database. After excluding patients with missing survival data, 43 patients were included in the survival analysis. Differential expression analysis was performed between advanced (T3-T4) and early (T1-T2) T-stage tumors using DESeq2. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox proportional hazards models. Associations between gene expression and T stage were evaluated, and the correlation between PRR11 and HEPACAM was assessed using Spearman correlation analysis.

Results: A total of 116 differentially expressed genes (DEGs) were identified between T3-T4 and T1-T2 tumors. While PRR11 was the most significantly upregulated gene in the overall DEGs analysis (log2FC =5.87), its expression showed no significant difference when directly comparing T3-T4 to T1-T2 groups (P=0.44). However, in multivariate analysis, high PRR11 expression emerged as an independent prognostic factor for worse overall survival (OS) [hazard ratio (HR) =2.74, P=0.005]. In contrast, HEPACAM, identified as the most significantly downregulated gene in the DEG analysis (log2FC =-5.10), exhibited paradoxically higher expression in advanced T-stage tumors compared to early-stage tumors (P=0.01). HEPACAM expression showed no significant association with OS (log-rank P=0.3). Notably, a significant negative correlation was observed between PRR11 and HEPACAM expression (Spearman's ρ =-0.375, P=0.01).

Conclusions: This study reveals divergent roles for PRR11 and HEPACAM in PM. PRR11 is a robust independent prognostic biomarker, despite its lack of correlation with local tumor invasion as defined by T stage. HEPACAM demonstrates a complex, stage-dependent expression pattern, suggesting a potential context-dependent role in late-stage tumor biology. The inverse correlation between these genes may reflect opposing cellular programs in PM progression. These findings provide new insights into the molecular heterogeneity of PM and highlight the importance of integrating multiple analytical approaches when interpreting transcriptomic data.

© AME Publishing Company.

In plain English

This study re-analyzed publicly available tumor gene-activity (RNA-sequencing) data and clinical records for 87 patients with pleural mesothelioma from The Cancer Genome Atlas (TCGA). It did not examine asbestos exposure. The authors compared tumors with more extensive local spread (stage T3–T4) against less extensive ones (T1–T2) and found 116 genes that differed. In that analysis, PRR11 was the most increased gene and HEPACAM the most decreased in advanced tumors. However, when the two groups were compared directly, PRR11 levels did not differ significantly (P=0.44), and HEPACAM was higher, not lower, in advanced tumors (P=0.01). Among 43 patients with survival data, those with high PRR11 had significantly worse overall survival. After accounting for tumor cell type and T stage in 42 patients, the hazard ratio for high versus low PRR11 was 3.11 (95% CI 1.48–6.57). HEPACAM levels were not significantly linked to survival. The authors concluded that PRR11 is an independent prognostic marker. They noted that treatment history was unavailable, the sample was small, and the findings need laboratory and outside-cohort confirmation.

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: Retrospective bioinformatic analysis of publicly available tumor RNA-sequencing and clinical data (TCGA mesothelioma cohort), including differential gene expression, Kaplan-Meier and Cox survival analysis, and correlation analysis
• Who was studied: 87 patients with pleural mesothelioma in The Cancer Genome Atlas database. 43 had complete survival data, and 42 were in the multivariate model after one patient with unknown histology was excluded. Location and years of diagnosis are not stated.
• Exposure: Asbestos exposure was not studied. The factors examined were tumor expression levels of the genes PRR11 and HEPACAM, compared between advanced (T3–T4) and early (T1–T2) T-stage tumors and in relation to survival.
• Main results:
  • 116 genes differed between advanced (T3–T4) and early (T1–T2) tumors: 100 higher and 16 lower in advanced tumors.
  • In this whole-genome comparison, PRR11 showed the largest increase in advanced tumors (log2 fold change 5.87).
  • In the same comparison, HEPACAM was the most significantly decreased gene in advanced tumors (log2 fold change −5.10).
  • In a direct comparison of early versus advanced tumors, PRR11 expression did not differ significantly (median 2 vs. 1, P=0.44).
  • In a direct comparison, HEPACAM expression was significantly higher in advanced than in early tumors (mean 285 vs. 129; median 7 vs. 3; P=0.01).
  • Among 43 patients with survival data, high PRR11 expression (n=20) was associated with worse overall survival than low expression (n=23) (log-rank P=0.003).
  • In the unadjusted (univariate) Cox analysis, the hazard ratio for high vs. low PRR11 expression was 2.74 (95% CI 1.35–5.59, P=0.005).
  • In the multivariate Cox model (n=42), adjusted for histological subtype and T stage, high PRR11 expression remained associated with worse overall survival (HR 3.11; 95% CI 1.48–6.57; P=0.002).
  • In the same model, non-epithelioid histology (biphasic or sarcomatoid) was associated with worse survival (HR 2.53; 95% CI 1.15–5.55; P=0.02).
  • In the same model, advanced T stage was not significantly associated with survival (HR 1.08; 95% CI 0.54–2.15; P=0.83).
  • Bootstrap resampling (1,000 resamples) gave a 95% CI of 1.56–7.69 for the PRR11 hazard ratio (high vs. low).
  • HEPACAM expression was not significantly associated with overall survival (log-rank P=0.30).
  • PRR11 and HEPACAM expression were negatively correlated (Spearman's rho −0.375; P printed as 1.2×10 to the −2, i.e. 0.012).
• The authors' conclusion: The authors concluded that PRR11 functions as an independent prognostic marker despite its complex association with T stage. They concluded that HEPACAM's stage-dependent expression may reflect adaptive responses during tumor progression, and that further experimental and independent-cohort validation is needed.
• Limitations the authors state:
  • TCGA data are cross-sectional, so changes in gene expression over time could not be assessed directly.
  • No laboratory validation was done in cell lines or tissue samples.
  • The small cohort size may limit statistical power.
  • Treatment history was unavailable, so the survival analysis could not adjust for it.
  • External validation of the T-stage findings was not possible with available public datasets.
  • The findings were not confirmed at the protein level.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Prognosis, Kaplan-Meier Curve, Multivariate Analysis, Overall Survival, Hazard Ratio.

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