74P - Characterization of ERBB2 variation and their association with immune response in solid tumours

Background

ERBB2, a receptor tyrosine kinase, is commonly affected by mutations, amplifications, and overexpression in various types of cancers. Drugs targeting ERBB2 are gradually being promoted to various types of cancer. However, the variation of ERBB2 in Chinese population and the relationship between ERBB2 high expression abnormalities and the tumor immune microenvironment remains unclear.

Methods

We utilized genomic data from over 10,000 pan-cancer Chinese populations in CbioPortal to detect somatic mutations and copy number variations. We also performed RNA sequencing date in TCGA (pan-cancer Atlas studies) to determine ERBB2 expression in diverse cancer types and evaluate the immune gene characteristics and content of tumor-infiltrating immune cell populations.

Results

A total of 309 ERBB2 amplifications, 169 ERBB2 substitution or insertion deletions, and 28 ERBB2 fusions or rearrangements were detected in 10,194 patients. The ERBB2 amplification rate of breast cancer (23.84%), gallbladder cancer (13.75%) and urothelium cancer (8.33%) ranked the top three among all cancer types. Among the co-mutated genes with ERBB2 mutations, TP53 (68.8%), CDK12 (34.7%), and RARA (18.7%) have the highest proportion of mutations. Furthermore, among 10,967 RNA datasets in TCGA, breast cancer, esophageal squamous cell carcinoma, and gastric adenocarcinoma displayed the highest average expression levels of ERBB2. Patients with high ERBB2 expression exhibited similar TMB values to those with low ERBB2 expression. However, in breast cancer, colon cancer, lung adenocarcinoma and lung squamous carcinoma, ERBB2 high expression was significantly associated with a higher proportion of activated mast cells, monocytes, and regulatory T cells, while the percentage of resting mast cells and M1 macrophages was notably lower.

Conclusions

Our study identified ERBB2 variation patterns among a cohort of Chinese solid tumor patients and demonstrated that ERBB2 abnormality high expression is associated with an activated immune system and a stronger inflammatory response. Our findings offer insights into the potential benefits of using immune checkpoint inhibitors for this type of patient.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.