Scholarlink

Background <p>Histopathological growth patterns (HGPs) have emerged as prognostic and predictive biomarkers in colorectal liver metastases (CLM). The desmoplastic/encapsulating HGP (EHGP) is associated with improved survival after surgery, whereas the replacement HGP (RHGP) is associated with poorer outcomes. However, HGPs can only be reliably assessed postoperatively, limiting their use as preoperative biomarkers. A deeper molecular understanding of HGPs could inform biomarker development and therapeutic strategies, including approaches to promote EHGP.</p> Methods <p>We applied in situ sequencing (ISS), an image-based spatial transcriptomics method, to map RNA expression in CLM tissue. Two custom gene panels (150 and 175 genes) were analysed in a chemonaïve cohort of resected CLM tissue from 19 patients with EHGP and RHGP.</p> Results <p>Distinct molecular programmes characterised the two patterns. RHGP was associated with damaged <i>SAA1</i><sup>+</sup> hepatocytes, <i>KRT18</i><sup>+</sup> neoplastic cells, and bifunctional hepatocyte-cholangiocyte cells. EHGP showed interferon-γ signalling, cytotoxic T-cell infiltration, and a fibrotic capsule with zonation-specific features: hepatic stellate cell activation, angiogenesis, and immune recruitment on the liver-facing side, and cancer-associated fibroblasts on the tumour-facing side.</p> Conclusions <p>These differences imply that growth patterns emerge from tumour-host driven interactions. They reveal new molecular features of the metastatic niche. These insights may inform the search for novel treatment strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Spatial transcriptomics differences of histopathological growth patterns in colorectal cancer liver metastases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月28日

查看全文
  • Maria Escriva Conde,
  • Axel Andersson,
  • Peter Vermeulen,
  • Mats Nilsson,
  • Hanna Nyström

摘要

Background

Histopathological growth patterns (HGPs) have emerged as prognostic and predictive biomarkers in colorectal liver metastases (CLM). The desmoplastic/encapsulating HGP (EHGP) is associated with improved survival after surgery, whereas the replacement HGP (RHGP) is associated with poorer outcomes. However, HGPs can only be reliably assessed postoperatively, limiting their use as preoperative biomarkers. A deeper molecular understanding of HGPs could inform biomarker development and therapeutic strategies, including approaches to promote EHGP.

Methods

We applied in situ sequencing (ISS), an image-based spatial transcriptomics method, to map RNA expression in CLM tissue. Two custom gene panels (150 and 175 genes) were analysed in a chemonaïve cohort of resected CLM tissue from 19 patients with EHGP and RHGP.

Results

Distinct molecular programmes characterised the two patterns. RHGP was associated with damaged SAA1+ hepatocytes, KRT18+ neoplastic cells, and bifunctional hepatocyte-cholangiocyte cells. EHGP showed interferon-γ signalling, cytotoxic T-cell infiltration, and a fibrotic capsule with zonation-specific features: hepatic stellate cell activation, angiogenesis, and immune recruitment on the liver-facing side, and cancer-associated fibroblasts on the tumour-facing side.

Conclusions

These differences imply that growth patterns emerge from tumour-host driven interactions. They reveal new molecular features of the metastatic niche. These insights may inform the search for novel treatment strategies.