Gastric cancer remains a leading cause of cancer-related mortality in India, where late diagnosis often limits treatment efficacy. Recent scientific breakthroughs have identified the role of circ6718 in gastric cancer as a critical diagnostic and prognostic biomarker found within small extracellular vesicles (sEVs). These vesicles facilitate intercellular communication, allowing tumors to manipulate their surroundings. Studies now confirm that hsa_circ_0006718 (circ6718) is significantly upregulated in gastric cancer patients, offering a new window for clinical intervention.

Furthermore, investigators examined how tissue-derived mesenchymal stem cells (GC-MSCs) contribute to the malignancy. They discovered that elevated sEV-circ6718 levels correlate strongly with advanced clinical stages and distant metastasis. Consequently, this circular RNA serves as more than just a marker; it is a functional driver of disease. Patients with higher expression levels typically face a poorer prognosis, highlighting its utility in risk stratification and early screening protocols.

The Mechanistic Axis of circ6718 in Gastric Cancer

Mechanistically, circ6718 acts as a competing endogenous RNA (ceRNA) by sequestering hsa-miR-561-3p. This action prevents the microRNA from suppressing SAAL1 (Serum amyloid A-like 1) expression. Therefore, the presence of circ6718 effectively derepresses SAAL1. In addition, SAAL1 enhances the transcriptional activity of PRRX1, which directly activates the TGFβ1 promoter. This specific pathway triggers the TGFβ1/Smad2/3 signaling cascade within the tumor microenvironment.

Consequently, this molecular axis drives the transdifferentiation of mesenchymal stem cells into cancer-associated fibroblasts (CAFs). These fibroblasts promote stromal remodeling, which increases tumor aggressiveness and facilitates the spread of cancer cells. However, identifying this sEV-circRNA-mediated crosstalk also reveals potential therapeutic targets. Inhibiting this axis could theoretically prevent the stromal changes that support tumor growth and metastasis in the stomach.

Frequently Asked Questions

How does circ6718 contribute to gastric cancer progression?

It functions as a molecular sponge for miR-561-3p. This leads to the upregulation of SAAL1 and PRRX1, which ultimately activates TGFβ1 signaling to transform normal cells into tumor-promoting fibroblasts.

Is circ6718 a reliable diagnostic tool?

Yes, research indicates that elevated sEV-derived circ6718 levels correlate with clinical stages and metastasis, making it a valuable biomarker for both early diagnosis and prognosis in gastric cancer.

What is the clinical significance of stromal remodeling in this context?

Stromal remodeling, driven by the transdifferentiation of stem cells into fibroblasts, creates a supportive environment for the tumor. This process enhances the aggressiveness of the cancer and promotes its ability to spread to distant organs.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Refer to the latest local and national guidelines for clinical practice.

References

Zhang F et al. Small Extracellular Vesicles-Derived Circ6718 Unlocks Stromal Remodeling and Serves as a Biomarker in Gastric Cancer. Adv Sci (Weinh). 2026 May 11. doi: 10.1002/advs.202521334. PMID: 42114147.

Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38.

Kristensen LS, et al. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675-691.