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Background <p>This study aimed to investigate the predictive value of serum CCL18 in the recurrence and invasiveness of pituitary neuroendocrine tumors (PitNETs). CCL18, a chemokine secreted mainly by tumor-associated macrophages, has been implicated in cancer progression, but its role in PitNETs remains unexplored.</p> Method <p>A total of 463 patients with PitNETs (110 recurrent and 353 non-recurrent) who underwent surgery at Beijing Tiantan Hospital between 2020 and 2022, along with 32 healthy controls, were retrospectively analyzed. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; R&amp;D Systems, Cat# DCC180). Clinical, radiological, and pathological parameters were assessed, and subgroup analyses were performed according to recurrence and invasiveness. Statistical analyses were conducted using SPSS 26.0, and receiver operating characteristic (ROC) curves were generated with GraphPad Prism 8.0. In addition, CCL18 mRNA expression in recurrence PitNETs and non-recurrence PitNETs tissues was validated by quantitative real-time PCR (qPCR).</p> Results <p>Serum CCL18 was higher in recurrent than non-recurrent PitNETs (median: 46253 vs. 27834 pg/mL, <i>P</i> &lt; 0.001) and elevated in invasive tumors. ROC analysis showed an AUC of 0.801 (95% CI: 0.752–0.850), with 84.9% sensitivity and 79.2% specificity for recurrence. CCL18 correlated with Knosp grade and Ki-67 index (<i>P</i> &lt; 0.001) and remained an independent predictor in multivariate analysis. qRT-PCR revealed CCL18 mRNA was upregulated in recurrence PitNET tissues versus non-recurrence PitNETs tissues (<i>P</i> &lt; 0.001), suggesting systemic elevation may reflect tumor microenvironment secretion. Recurrent invasive PitNETs had the highest CCL18 levels.</p> Conclusions <p>Serum CCL18 is associated with PitNETs recurrence and invasiveness and may serve as a non-invasive biomarker. Combined tissue and serum assessment could improve risk stratification and prognostic evaluation.</p>

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Predictive value of serum CCL18 for recurrence and invasiveness in pituitary neuroendocrine tumors

  • 期刊论文

  • 发表日期：

    2026年1月27日

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  • Yang Jiao,
  • Guoge Li,
  • Kelin Chen,
  • Chunqing Shao,
  • Zhijun Yang,
  • Guojun Zhang

摘要

Background

This study aimed to investigate the predictive value of serum CCL18 in the recurrence and invasiveness of pituitary neuroendocrine tumors (PitNETs). CCL18, a chemokine secreted mainly by tumor-associated macrophages, has been implicated in cancer progression, but its role in PitNETs remains unexplored.

Method

A total of 463 patients with PitNETs (110 recurrent and 353 non-recurrent) who underwent surgery at Beijing Tiantan Hospital between 2020 and 2022, along with 32 healthy controls, were retrospectively analyzed. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Cat# DCC180). Clinical, radiological, and pathological parameters were assessed, and subgroup analyses were performed according to recurrence and invasiveness. Statistical analyses were conducted using SPSS 26.0, and receiver operating characteristic (ROC) curves were generated with GraphPad Prism 8.0. In addition, CCL18 mRNA expression in recurrence PitNETs and non-recurrence PitNETs tissues was validated by quantitative real-time PCR (qPCR).

Results

Serum CCL18 was higher in recurrent than non-recurrent PitNETs (median: 46253 vs. 27834 pg/mL, P < 0.001) and elevated in invasive tumors. ROC analysis showed an AUC of 0.801 (95% CI: 0.752–0.850), with 84.9% sensitivity and 79.2% specificity for recurrence. CCL18 correlated with Knosp grade and Ki-67 index (P < 0.001) and remained an independent predictor in multivariate analysis. qRT-PCR revealed CCL18 mRNA was upregulated in recurrence PitNET tissues versus non-recurrence PitNETs tissues (P < 0.001), suggesting systemic elevation may reflect tumor microenvironment secretion. Recurrent invasive PitNETs had the highest CCL18 levels.

Conclusions

Serum CCL18 is associated with PitNETs recurrence and invasiveness and may serve as a non-invasive biomarker. Combined tissue and serum assessment could improve risk stratification and prognostic evaluation.