Site-specific protein biomarkers in gastric cancer: a comprehensive review of novel biomarkers and clinical applications

ABSTRACT

Introduction

Gastric cancer (GC) is the fifth most common cancer and the fourth leading cause of cancer-related death worldwide, thus representing a significant global health burden. Early detection and monitoring of GC are essential to improve patient outcomes. While traditional cancer biomarkers such as carcinoembryonic antigen, carbohydrate antigen (CA) 19–9, and CA 72–4 are widely used, their limited sensitivity and specificity necessitate the exploration of alternative biomarkers.

Areas covered

This review comprehensively analyzes the landscape of GC protein biomarkers identified from 2019 to 2022, with a focus on tissue, blood, urine, saliva, gastric juice, ascites, and exhaled breath as sample sources. We address the potential clinical applications of these biomarkers in early diagnosis, monitoring recurrence, and predicting survival and therapeutic response of GC patients.

Expert opinion

The discovery of novel protein biomarkers holds great promise for improving the clinical management of GC. However, further validation in large, diverse cohorts is needed to establish the clinical utility of these biomarkers. Integrating these biomarkers with existing diagnostic and monitoring approaches will likely lead to improved personalized treatment plans and patient outcomes.

KEYWORDS:

• gastric cancer
• biomarker
• protein
• liquid biopsy
• blood
• tissue
• urine

Article highlights

• GC is a major global health problem with poor outcomes in the advanced stage because of high recurrence rates and chemotherapy resistance. Developing effective biomarkers is critical to improving GC prognosis and facilitating early detection.

• Protein biomarkers, including established markers such as CEA, CA19-9, and CA72-4, play an essential role in GC diagnosis, prognosis, and treatment selection. Biomarkers such as HER2 and PD-L1 have also emerged as therapeutic targets.

• Tissue-based biomarkers provide valuable insights into tumor aggressiveness, molecular profiles, and patient-specific treatment response. In contrast, blood-based biomarkers offer a more accessible and widely accepted source for routine testing.

• Alternative sample sources such as urine, saliva, gastric juice, ascites, and exhaled breath have been explored to expand the range of potential biomarkers.

• The current landscape of GC protein biomarkers holds promise for improving patient outcome; however, further research is needed to validate their clinical utility, standardize methodologies, and develop cost-effective, noninvasive detection techniques.

Acknowledgments

We thank Gabrielle White Wolf, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Declaration of interest

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.