Molecular diagnosis of Esophageal squamous cell carcinoma

Introduction Esophageal cancer is the eighth most common cancer and a leading cause of cancer-related deaths worldwide. Esophageal squamous cell carcinoma (ESCC) is the most prevalent type of esophageal cancer, contributing significantly to the global cancer burden. The prognosis for ESCC remains poor, particularly when diagnosed at advanced stages, with a five-year survival rate of less than ۳۰%. Histological changes from dysplasia to invasive carcinoma are influenced by genetic mutations, environmental factors, and lifestyle habits such as alcohol consumption and smoking. Molecular alterations, including cytokine dysregulation, aberrant DNA methylation, and specific microbial changes, are linked to ESCC progression. Given the limitations of invasive endoscopic screening methods, there is a growing need for non-invasive molecular techniques, including biomarker detection, to improve early diagnosis and treatment outcomes for ESCC patients. This review explores key molecular markers and diagnostic strategies for advancing the early detection of ESCC. Methods A literature search was conducted using PubMed, Scopus, and Web of Science databases, covering articles published up to September ۲۰۲۴. Keywords such as " Esophageal cancer," and " Molecular diagnosis," were used. Results: The molecular diagnosis of esophageal squamous cell carcinoma (ESCC) relies heavily on understanding genetic alterations. DNA and RNA markers, such as circulating tumor DNA (ctDNA) and microRNAs (e.g., miR-۱۵۵), have emerged as important tools for early detection and prognosis of ESCC. Aberrant expression of these nucleic acids, particularly linked to genetic mutations, plays a critical role in identifying malignant changes in esophageal tissues. Proteins like p۵۳, HGF, and bFGF, as well as cytokines including VEGF, IL-۲, and IFN-γ, are valuable biomarkers for diagnosing ESCC and predicting patient outcomes. Their dysregulation can signal tumor growth, metastasis, and angiogenesis, while immunohistochemistry methods can detect such proteins in formalin-fixed tissue samples, providing further diagnostic insight. Multi-omics approaches, particularly aberrant DNA methylation patterns, offer promising avenues for ESCC diagnosis. These changes serve as diagnostic and prognostic markers, while advancements in artificial intelligence (AI) are enhancing the analysis of complex multi-omics data, improving accuracy in predicting disease progression. The role of the microbiome, especially changes in oral bacterial composition, is gaining attention in ESCC diagnostics. Increased levels of Streptococcus anginosus and Treponema denticola have been linked to esophageal tumorigenesis, providing a potential non-invasive diagnostic marker. Conclusion: Molecular diagnostics in esophageal squamous cell carcinoma (ESCC) have advanced significantly, offering promising tools such as genetic markers, protein biomarkers, cytokine profiling, multi-omics, and microbiome analysis. These techniques, combined with artificial intelligence, hold great potential for improving early detection, prognosis, and personalized treatment. However, the complexity of ESCC demands a more systematic approach. Future studies should focus on integrating these molecular technologies into comprehensive diagnostic models, validating them across diverse populations, and developing non-invasive, cost-effective methods. A deeper understanding of ESCC’s molecular landscape will pave the way for more accurate, early diagnosis and improved patient outcomes.

کلیدواژه ها:

Esophageal squamous cell carcinoma ، ESCC ، Molecular diagnosis ، Cytokines ، microbiome