The Role of MicroRNA-200 Family in Gastrointestinal Cancers.

Introduction: Gastrointestinal cancers, including esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, are a major health burden worldwide, characterized by high incidence and mortality rates. Traditional diagnostic methods are not satisfactory. The compliance of patients with endoscopic examinations is poor, and the sensitivity and specificity of conventional tumor markers are also not high. Liquid biopsy, especially the detection of exosomal microRNAs (miRNAs), as a promising alternative method, has emerged, among which the miR-200 family has been identified as a key regulatory factor in the pathogenesis of gastrointestinal cancers.

Methods: A literature search was conducted from 2002 to 2025, and the keywords used included "gastrointestinal cancer", "miR-200 family", and "exosomal miRNA". The studies involved included those on the role of miR-200 in gastrointestinal cancers, as well as research on exosomal miR-200 as a biomarker or therapeutic target. Inclusion criteria include: original studies published in English and peer-reviewed, which explored the biological, diagnostic, prognostic, or therapeutic effects of the miR-200 family in gastrointestinal cancers, and provided the complete papers that are accessible. If the research is a review, a conference summary, an editorial, a duplicate dataset, or lacks sufficient experimental or clinical data related to miR-200, it will be excluded. This literature search was conducted in the PubMed database. After screening, a total of 248 articles were obtained, and finally, 133 studies were included in the analysis. This review adhered to the guidelines of SANRA and employed a narrative research method. The key findings were qualitatively synthesized to summarize the mechanism of miR-200 and its clinical relevance.

Results: MicroRNA-200 regulates the occurrence and development of gastrointestinal cancers by modulating epithelial-mesenchymal transition (EMT), angiogenesis, cancer stem cell properties, and chemotherapy resistance. Its expression in tumor tissues is closely related to clinical pathological features, prognosis, and treatment response. Furthermore, the miR-200 present in exosomes exhibits extremely high stability in circulation and specificity towards cancer.

Discussion: Studies have shown that miR-200 family regulates the occurrence and development of gastrointestinal cancer by targeting epithelial-mesenchymal transition, angiogenesis, and other characteristics, and its expression is related to clinicopathological characteristics and prognosis. Exosomal miR-200 family has shown good diagnostic performance in gastrointestinal malignancies. In an independent validation cohort, the AUC of combined miR-200a-3p and miR200b-3p expression in pancreatic ductal adenocarcinoma (PDAC) was 0.97, with a sensitivity of 100% and a specificity of 88%. Notably, combining this miRNA combination with CA19-9 further improved diagnostic accuracy, increasing the AUC of the combined model from 0.86 for CA19-9 alone to 0.997. In addition, miR-200c had a moderate but significant diagnostic and prognostic value for GC, with a combined AUC of 0.75, a sensitivity of 0.74, and a specificity of 0.66. Limitations such as the heterogeneity of studies and the unclear mechanism of exosome packaging can be alleviated by standardized protocols. Future studies should focus on largescale multi-center trials, in-depth exploration of molecular mechanisms, and standardization of experimental workflow.

Conclusion: Exosomal miR-200 overcomes the limitations of traditional diagnosis and is expected to become a biomarker and therapeutic target for gastrointestinal tumors. The miR-200 family had the strongest diagnostic evidence in pancreatic ductal adenocarcinoma (AUC = 0.97, sensitivity = 100%, specificity = 88%) and gastric cancer (AUC = 0.75, sensitivity = 74%, specificity = 66%). These data highlight its translational potential as a clinically relevant biomarker for early and non-invasive gastrointestinal cancer detection. Validation in large cohorts and the development of targeted therapies will be essential to improve patient outcomes.