# WFIKKN2 is secreted and elevated in blood plasma of HER2-positive breast cancer patients – implications in cancer surveillance and recurrence monitoring

**Authors:** Amir Sabbaghian, Fei Xie, Xiao Fang Wang, Zhen Yang, Ming Chen Zhang, Ting Gang Chew, Shu Wang, Yoon Pin Lim

PMC · DOI: 10.1186/s40364-025-00853-4 · Biomarker Research · 2025-11-05

## TL;DR

This study identifies WFIKKN2 as a blood plasma protein that is elevated in HER2-positive breast cancer patients, suggesting its potential for cancer surveillance and recurrence monitoring.

## Contribution

The study discovers WFIKKN2 as a novel, highly sensitive blood-based biomarker for HER2-positive breast cancer.

## Key findings

- WFIKKN2 was identified as a novel blood plasma protein associated with HER2-positive breast cancer.
- ELISA analysis showed WFIKKN2 has 89% sensitivity and 60% specificity in detecting HER2+ breast cancer.
- WFIKKN2's high sensitivity makes it suitable for post-treatment surveillance and recurrence monitoring.

## Abstract

Current methods for post-treatment cancer surveillance and recurrence monitoring rely mainly on biophysical imaging methods like CT and MRI. Limitations associated with these approaches include risk of radiation, high cost and sophistication in operation. Minimally invasive blood test is a very attractive alternative but there is no biomarker that is of sufficient sensitivity for this purpose. In this study, we attempted to discover novel breast cancer-associated blood plasma proteins that can fill this gap. We tested the hypothesis that genes that are co-amplified HER2 can be used as a surrogate biomarker for detection of HER2+ breast cancer. Following identification of HER2-coamplified genes via copy number variation analysis, a series of bioinformatic tools were used that eventually led to the identification of WFIKKN2 as a novel cancer-associated blood plasma protein. ELISA analysis of more than 120 plasma samples from non-cancer and cancer patients with HER2+ breast cancer revealed WFIKKN2 to have sensitivity and specificity of up to 89% and 60%, respectively. While not ideal as a diagnostic biomarker due to its moderate specificity, the high sensitivity of WFIKKN2 is suitable for the purpose of post-treatment surveillance and recurrence monitoring. The data warrants WFIKKN2 to be further evaluated through clinical studies to validate its clinical utility.

The online version contains supplementary material available at 10.1186/s40364-025-00853-4.

## Linked entities

- **Genes:** WFIKKN2 (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2) [NCBI Gene 124857], ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064]
- **Proteins:** WFIKKN2 (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2)
- **Diseases:** breast cancer (MONDO:0004989), HER2-positive breast cancer (MONDO:0006244)

## Full-text entities

- **Genes:** ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, WFIKKN2 (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2) [NCBI Gene 124857] {aka GASP-1, WFDC20B, WFIKKNRP, hGASP-1}
- **Diseases:** breast cancer (MESH:D001943), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12590779