Vasohibin-1 Expression Can Predict Pathological Complete Remission of Advanced Bladder Cancer with Neoadjuvant Chemotherapy

Ann Surg Oncol. 2024 May;31(5):2951-2958. doi: 10.1245/s10434-024-15009-1. Epub 2024 Feb 20.

Abstract

Background and purpose: Neoadjuvant chemotherapy (NAC) is a well-established standard practice in invasive bladder cancer (BCa), however patient selection remains challenging. High expression of vasohibin-1 (VASH1), an endogenous regulator of angiogenesis, has been reported in high-grade and advanced BCa; however, its prognostic value for chemotherapy outcomes remains unexplored. In this study, we sought to identify biomarkers of chemotherapy response focusing on the relationship between angiogenesis and tissue hypoxia.

Methods: Forty Japanese patients with BCa who underwent NAC and radical cystectomy were included in the present analysis. We compared the immunohistochemical expression of CD34, VASH1, and carbonic anhydrase 9 (CA9) between patients who achieved tumor clearance at operation (ypT0) and those with residual disease after cystectomy.

Results: There were 19 patients in the ypT0 group, while the remaining 21 patients had residual tumors at operation. Patients in the ypT0 group had high microvessel density (p = 0.031), high VASH1 density (p < 0.001), and stronger CA9 staining (p = 0.046) than their counterparts. Multivariate analysis identified microvessel and VASH1 density as independent predictive factors for pathological ypT0 disease (p = 0.043 and 0.002, respectively). The 5-year recurrence-free survival rate was higher in the high VASH1 density group than in the low VASH1 density group (66.3% vs. 33.3%, p = 0.036).

Conclusion: VASH1 density is a potential therapeutic biomarker for chemotherapy response in BCa.

Keywords: Angiogenesis; Biomarkers; Bladder cancer; Chemotherapy; Pathological outcome.

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cystectomy
  • Humans
  • Neoadjuvant Therapy*
  • Pathologic Complete Response
  • Prognosis
  • Retrospective Studies
  • Urinary Bladder Neoplasms* / pathology

Substances

  • VASH1 protein, human
  • Cell Cycle Proteins