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Background <p>Inhibin subunit beta B (<i>INHBB</i>), a member of the TGF-β superfamily, has emerged as a potential regulator of tumor progression and immune modulation. However, its clinical and immunological significance in colorectal cancer (CRC) remains unclear.</p> Methods <p>This study evaluated <i>INHBB</i> mRNA expression in 248 CRC cases using RNA in situ hybridization (RNAscope), immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq). Associations with clinicopathological parameters, tumor-infiltrating immune cells, and prognosis were analyzed.</p> Results <p><i>INHBB</i> was primarily expressed in tumor epithelial cells and weakly in stromal cells, but was negligible in normal mucosa. High <i>INHBB</i> expression correlated significantly with venous invasion, lymph node metastasis, advanced TNM stage, and reduced tumor-infiltrating lymphocytes. IHC revealed marked decreases in CD4⁺, CD8⁺, and FOXP3⁺ T cells and increased CD163⁺ tumor-associated macrophages in <i>INHBB</i> high tumors, indicating an immunosuppressive tumor microenvironment (TME). Kaplan–Meier analysis showed that high <i>INHBB</i> expression was associated with worse overall survival and recurrence-free survival, but was not an independent prognostic factor in multivariate models.</p> Conclusion <p><i>INHBB</i> is predominantly expressed in tumor epithelium and is associated with aggressive features, poor prognosis, and the formation of an immune-cold, macrophage-rich TME in CRC. These findings suggest that <i>INHBB</i> may be a potential biomarker for immune evasion and a target for novel immunotherapeutic strategies in CRC.</p>

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High INHBB Expression Shapes an Immunosuppressive Tumor Microenvironment and Predicts Poor Prognosis in Colorectal Carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月1日

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  • Hiroshi Sawaguchi,
  • Takeshi Uehara,
  • Mai Iwaya,
  • Shiho Asaka,
  • Tomoyuki Nakajima,
  • Shotaro Komamura,
  • Shunsuke Imamura,
  • Yugo Iwaya,
  • Shinsuke Sugenoya,
  • Masato Kitazawa,
  • Yuji Soejima,
  • Hiroyoshi Ota,
  • Tadanobu Nagaya

摘要

Background

Inhibin subunit beta B (INHBB), a member of the TGF-β superfamily, has emerged as a potential regulator of tumor progression and immune modulation. However, its clinical and immunological significance in colorectal cancer (CRC) remains unclear.

Methods

This study evaluated INHBB mRNA expression in 248 CRC cases using RNA in situ hybridization (RNAscope), immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq). Associations with clinicopathological parameters, tumor-infiltrating immune cells, and prognosis were analyzed.

Results

INHBB was primarily expressed in tumor epithelial cells and weakly in stromal cells, but was negligible in normal mucosa. High INHBB expression correlated significantly with venous invasion, lymph node metastasis, advanced TNM stage, and reduced tumor-infiltrating lymphocytes. IHC revealed marked decreases in CD4⁺, CD8⁺, and FOXP3⁺ T cells and increased CD163⁺ tumor-associated macrophages in INHBB high tumors, indicating an immunosuppressive tumor microenvironment (TME). Kaplan–Meier analysis showed that high INHBB expression was associated with worse overall survival and recurrence-free survival, but was not an independent prognostic factor in multivariate models.

Conclusion

INHBB is predominantly expressed in tumor epithelium and is associated with aggressive features, poor prognosis, and the formation of an immune-cold, macrophage-rich TME in CRC. These findings suggest that INHBB may be a potential biomarker for immune evasion and a target for novel immunotherapeutic strategies in CRC.