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High-Plex Digital Spatial Profiling Identified Prolactin-Induced Protein mRNA Associated With Response and Survival

Yuhang Han1, Danyang Ji1, Yujing Tan1

  • 1Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.

Medcomm
|December 1, 2025
PubMed

Insights

Predictive biomarkers for everolimus (EVE) in advanced breast cancer are needed. Prolactin-induced protein (PIP) mRNA expression and immune-stromal features identify patients resistant to EVE, suggesting PIP as a potential predictive biomarker.

Area of Science:

  • Oncology
  • Translational Research
  • Biomarker Discovery

Background:

  • Everolimus (EVE) combined with letrozole is an approved treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
  • Predictive biomarkers for EVE efficacy in ABC remain undefined.
  • Digital spatial profiling (DSP) offers a method to explore the tumor microenvironment for predictive markers.

Purpose of the Study:

  • To identify predictive biomarkers for EVE efficacy in HR+/HER2- ABC using DSP.
  • To investigate immune and transcriptomic markers associated with response or resistance to EVE plus letrozole therapy.
  • To evaluate the potential of Prolactin-induced protein (PIP) mRNA as a predictive biomarker.

Main Methods:

  • Phase 2 MIRACLE trial data from 21 patients with HR+/HER2- ABC treated with EVE plus letrozole.
  • Digital spatial profiling (DSP) of pretreatment tumor samples.
  • Analysis of immune and transcriptomic markers across tumor, leukocyte, and stroma compartments.

Main Results:

  • Responders showed higher fibroblast infiltration, while non-responders had increased neutrophils.
  • Prolactin-induced protein (PIP) mRNA expression was significantly elevated in non-responders.
  • Elevated PIP mRNA expression correlated with EVE resistance and unfavorable progression-free survival (PFS).

Conclusions:

  • Specific immune-stromal features and PIP mRNA expression are associated with resistance to EVE in HR+/HER2- ABC.
  • PIP mRNA shows potential as a spatially resolved predictive biomarker for patient stratification.
  • Further validation of PIP could aid in optimizing EVE treatment strategies for advanced breast cancer.
Keywords:
HR+/HER2− advanced breast cancerPIP mRNAeverolimushigh‐plex digital spatial profilingletrozole

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