Investigating the Co-Expression Rate of HER2 and HER3 Biomarkers in Cancer Patients - A Systematic Review and Meta-Analysis

Sep 21, 2026

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Co-expression of the HER2/HER3 heterodimer is highlighted as a key oncogenic unit linked to greater tumor aggressiveness and poorer overall survival, motivating therapies that target both biomarkers. This systematic review and meta-analysis collects co-expression data across multiple cancer types using searches of PubMed, Scopus, Embase, and Web of Science. Event rates with 95% confidence intervals are computed, with heterogeneity, subgroup, and meta-regression analyses by region, age, and gender, and a PROSPERO-registered protocol.

LanguageEnglish

CategoryResearch & Report

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Pages12

Reading Time30 min

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Abstract

Introduction

Materials and Methods

Search strategy

REVIEW Editorial Process: Submission:03/08/2024 Acceptance:09/01/2024 Investigating the Co-Expression Rate of HER2 and HER3 Biomarkers in Cancer Patients: A Systematic Review and Meta-Analysis Reza Hassanzadeh Makoui1, Shiva Fekri2, NegarAnsari3, Masoud Hassanzadeh Makoui4 * Abstract Background: Many types of cancer express the HER2/HER3 heterodimer, which is a crucial oncogenic unit. Research has shown that when these two biomarkers are expressed together, it correlates with higher tumor aggressiveness and lower overall survival rate. Therefore, many therapies have been developed to target both biomarkers simultaneously. This study aims to collect data on the co-expression levels of these biomarkers across different types of cancers. Methods: A comprehensive search was conducted across PubMed, Scopus, Embase, and Web of Science databases to identify relevant studies. The event rates and their corresponding 95% confidence intervals were calculated. Heterogeneity, subgroup, and meta-regression analyses were conducted based on patients’ residency region, age, and gender. The protocol of this study was registered in PROSPERO under ID: CRD42024504256 . Results: We have detected 60 studies that met all of the inclusion criteria for our research. Out of these, we have focused on a total of 19 studies (with 6,079 participants) related to breast cancer, 9 studies (with 829 participants) related to lung cancer, 6 studies (with 1423 participants) related to gastric cancer, and 4 studies (with 802 participants) related to colorectal cancer for conducting our meta-analysis. According to our results, the co-expression rate of HER2 and HER3 in breast cancer patients is 18.5%(95%CI 11.7–27.9), in colorectal cancer patients is 17.1%(95%CI 2.4–63.4), in gastric cancer patients is 11.3%(95%CI 4.2–17.2), and in lung cancer patients is 12.7%(95%CI 5.2–22.8) . The co-expression of HER2 and HER3 in lung cancer has a significant association with patients’ gender (P=0.038) . Conclusion: The study found that HER2 and HER3 biomarkers, which are targets for different therapies, are co-expressed in various types of cancer. Keywords: Cancer-co-expression-HER2-HER3-meta-analysis Asian Pac J Cancer Prev, 25 (9), 2979-2990 Introduction The human epidermal growth factor receptor (HER) receptor family is widely recognized for its significant impact on various forms of human cancer pathogenesis [1]. The HER family consists of four members, with HER2 and HER3 being the two most significant ones [2] . Upon interacting with extracellular ligands, these receptors initiate various downstream pathways that govern a wide range of processes, including differentiation, migration, proliferation, and survival [3] . The HER2 receptor is found on the cell membrane and can activate tyrosine kinases. The overexpression of the HER2 receptor plays a crucial role in the process of transformation and tumorigenesis [4] . Different subcategories of human cancers have been observed to exhibit varying levels of HER2 overexpression, and assessing the HER2 status is essential in determining the suitability of anti-HER2 targeted therapies [5] . Nevertheless, HER3 is unique among the members of the HER family in that it lacks tyrosine kinase activity. Recognizing HER3’s role in tumor growth, rapid multiplication, and drug resistance in cancers like breast and non-small cell lung cancer highlights the importance of disabling HER3 and its signaling pathways to overcome treatment resistance and improve outcomes for cancer patients [6] . As there is no known ligand for HER2 and HER3 has a faulty intrinsic tyrosine kinase, HER2 prefers to combine with HER3 to form heterodimers [7] . The HER2/HER3 heterodimer is a potent oncogenic unit that is linked to various cancers’progression and poor overall survival [8] . The evasion of apoptosis is significantly influenced by the interaction between HER2 and HER3, which is reliant on 1Department of Cardiology, School of Medici

FAQs

What is the main goal of this systematic review and meta-analysis?

To collect and analyze data on the co-expression levels of HER2 and HER3 across different types of cancer.

Which databases were searched to identify eligible studies?

PubMed, Scopus, Embase, and Web of Science were searched to find relevant studies.

How many studies and participants were included in the meta-analysis for the main cancer types?

A total of 19 studies were used, including 6,079 participants for breast cancer, 829 for lung cancer, 1,423 for gastric cancer, and 802 for colorectal cancer.

Sep 21, 2026

Uploaded by Aurelia