Related Experiment Video
Updated: Dec 1, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy
Ziteng Li1, Siyuan Chen1, Wanjing Feng1
1Department of Medical Oncology, Fudan University Shanghai Cancer Center, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Background:
The prevalence of HER2 alterations in pan-cancer indicates a broader range of application of HER2-targeted therapies; however, biomarkers for such therapies are still insufficient and limited to breast cancer and gastric cancer.
Methods:
Using multi-omics data from The Cancer Genome Atlas (TCGA), the landscape of HER2 alterations was exhibited across 33 tumor types. A HER2 index was constructed using one-class logistic regression (OCLR). With the predictive value validated in GEO cohorts and pan-cancer cell lines, the index was then applied to evaluate the HER2-enriched expression pattern across TCGA pan-cancer types.
Findings:
Increased HER2 somatic copy number alterations (SCNAs) could be divided into two patterns, focal- or arm-level. The expression-based HER2 index successfully distinguished the HER2-enriched subtype from the others and provided a stable and superior performance in predicting the response to HER2-targeted therapies both in breast tumor tissue and pan-cancer cell lines. With frequencies varying from 12.0% to 0.9%, tumors including head and neck squamous tumors, gastrointestinal tumors, bladder cancer, lung cancer and uterine tumors exhibited high HER2 indices together with HER2 amplification or overexpression, which may be more suitable for HER2-targeted therapies. The BLCA.3 and HNSC.Basal were the most distinguishable subtypes within bladder cancer and head and neck cancer respectively by HER2 index, implying their potential benefits from HER2-targeted therapies.
Interpretation:
As a pan-cancer predictive biomarker of HER2-targeted therapies, the HER2 index could help identify potential candidates for such treatment in multiple tumor types by combining with HER2 multi-omics features. The discoveries of our study highlight the importance of incorporating transcriptional pattern into the assessment of HER2 status for better patient selection.
Funding:
The National Key Research and Development Program of China; Clinical Research and Cultivation Project of Shanghai ShenKang Hospital Development Center.
Insights
A new HER2 index can identify more cancer patients eligible for HER2-targeted therapies beyond breast and gastric cancers. This biomarker aids in selecting patients across various tumor types for improved treatment outcomes.
Area of Science:
- Oncology
- Genomics
- Biomarker Discovery
Background:
- HER2 alterations are prevalent across cancers, suggesting broad applicability of HER2-targeted therapies.
- Current biomarkers are limited to breast and gastric cancers, necessitating broader tools.
Purpose of the Study:
- To explore the landscape of HER2 alterations in a pan-cancer context.
- To develop and validate a novel HER2 index as a predictive biomarker for HER2-targeted therapies.
Main Methods:
- Utilized multi-omics data from The Cancer Genome Atlas (TCGA) for pan-cancer analysis.
- Constructed a HER2 index using one-class logistic regression (OCLR) and validated it in independent cohorts and cell lines.
- Applied the HER2 index to evaluate HER2-enriched expression patterns across 33 tumor types.
Main Results:
- HER2 somatic copy number alterations (SCNAs) were classified into focal- or arm-level patterns.
- The HER2 index effectively distinguished HER2-enriched subtypes and predicted therapy response in breast and pan-cancer cell lines.
- Tumors like head and neck, gastrointestinal, bladder, lung, and uterine cancers showed high HER2 indices, indicating potential for HER2-targeted therapies.
Conclusions:
- The HER2 index serves as a pan-cancer predictive biomarker for HER2-targeted therapies.
- Incorporating transcriptional patterns into HER2 status assessment improves patient selection for targeted treatments.
More Related Videos
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
08:28Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
