# Heme Oxygenase-1 Expression as a Prognostic Marker in Early-Stage HCC Undergoing Resection or Liver Transplantation

**Authors:** Ramona Cadar, Alin Mihai Vasilescu, Ana Maria Trofin, Alexandru Grigorie Nastase, Mihai Zabara, Cristina Muzica, Corina Lupascu Ursulescu, Mihai Danciu, Andrei Pascu, Iulian Buzincu, Delia Ciobanu, Ianole Victor, Cristian Dumitru Lupascu

PMC · DOI: 10.3390/life15101589 · Life · 2025-10-11

## TL;DR

This study explores whether HO-1 expression in liver cancer can predict patient outcomes after surgery or liver transplants.

## Contribution

The study identifies HO-1 as a potential marker for aggressive tumor features in early-stage liver cancer, though not for overall survival.

## Key findings

- High HO-1 expression is linked to hepatitis C virus, vascular invasion, and anticoagulant therapy.
- HO-1 expression does not correlate with overall survival in HCC patients.
- Solid tumor growth and specific AFP levels are associated with worse survival outcomes.

## Abstract

Background: Hepatocellular carcinoma (HCC) is a prevalent malignancy with high mortality, often arising in the context of chronic liver diseases. Heme oxygenase-1 (HO-1), an inducible enzyme involved in heme degradation, has been implicated in both hepatoprotection and tumor progression. This study evaluates the expression of HO-1 in HCC and its association with clinicopathological features and patient survival. Materials and Methods: We retrospectively analyzed 58 HCC cases diagnosed between 2018 and 2023 at “Sf. Spiridon” Emergency County Hospital, Iasi. HO-1 expression was assessed immunohistochemically and quantified using a semi-quantitative immunoreactivity score (IRS). Statistical correlations between HO-1 expression and clinical, pathological, and survival parameters were evaluated using univariate analysis, ROC curves, and Kaplan–Meier survival models. Results: High HO-1 expression (IRS > 1) was significantly associated with hepatitis C virus etiology (p = 0.004, V = 0.381), vascular invasion (p = 0.019, V = 0.309) and perioperative anticoagulant therapy (p = 0.007, V = 0.352). However, HO-1 expression did not correlate with overall survival (OS). In contrast, solid growth pattern (p = 0.030) and serum α-fetoprotein levels of 10–99 ng/mL (p = 0.022) were negatively associated with OS. Conclusions: HO-1 expression in HCC was found to be associated with vascular invasion, but not with overall survival. While this may indicate a potential link to certain aggressive tumor features, the overall role of HO-1 in HCC biology remains unclear. These findings suggest that HO-1 should be considered an exploratory rather than definitive prognostic marker, and further research is warranted to clarify its function and potential utility, including investigation of its detectability in biological fluids for non-invasive monitoring.

## Linked entities

- **Genes:** TED4 (Plant heme oxygenase (decyclizing) family protein) [NCBI Gene 817208], HMOX1 (heme oxygenase 1) [NCBI Gene 3162]
- **Diseases:** Hepatocellular carcinoma (MONDO:0007256), HCC (MONDO:0007256)

## Full-text entities

- **Genes:** AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}
- **Diseases:** chronic liver diseases (MESH:D008107), malignancy (MESH:D009369), HCC (MESH:D006528)
- **Chemicals:** heme (MESH:D006418)
- **Species:** Homo sapiens (human, species) [taxon 9606], hepatitis C virus [taxon 11103]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12565677/full.md

## References

62 references — full list in the complete paper: https://tomesphere.com/paper/PMC12565677/full.md

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Source: https://tomesphere.com/paper/PMC12565677