Exosome P4HA3 is a Potential Diagnostic and Prognostic Biomarker in Gastric Cancer

Background: Gastric cancer (GC) remains a global health challenge due to its high mortality rate and the lack of specific diagnostic methods. The accuracy of early diagnosis significantly hinders effective treatment, necessitating advanced techniques to dissect its complexity. Exosomes are extracellular nano-sized vesicles and secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. However, the regulatory mechanism of exosomes in GC remains to be further explored. This study leverages transcriptome analysis to explore the relationship between exosomes and GC and clarify its potential mechanisms, in order to identify novel prognostic markers and therapeutic targets in GC. Methods: The Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) were used to verify the expression of P4HA3 in GC tissues and exosomes. ROC curve and Kaplan-Meier curve were constructed to determine the diagnostic value and prognostic significance of P4HA3. The correlation between P4HA3 and GC stages were analyzed and its functional enrichment was evaluated. Next, the expression of P4HA3 in other cancers were evaluated by pan-cancer analysis. Finally, the expression of P4HA3 in vivo and in vitro in GC and its regulatory mechanism were further explored. Results: P4HA3 was widely expressed in GC and other cancer tissues, which was associated with the stages and poor prognosis of GC. The results of P4HA3 enrichment analysis and immune infiltration indicate that P4HA3 may participate in the epithelial mesenchymal transformation (EMT) process of GC, the results were confirmed in our subsequent mechanism verification. Finally, the experimental results in vivo and in vitro showed that P4HA3 was also upregulated in GC. It indicated that exosome P4HA3 may be a potential diagnostic and prognostic biomarker in GC, which may promote EMT through the COL1A1 cascade and enhance the invasion and metastasis ability of GC cells. Conclusion: P4HA3 is highly expressed in exosomes and significantly associated with poor prognosis of GC, which may promote EMT through the COL1A1 cascade and enhance the invasion and metastasis ability of GC cells. In summary, we demonstrated that P4HA3 is a promising diagnostic and therapeutic biomarker for GC.