Role Of Critical Molecules In Proliferation and Apoptosis In Tumoral And Peri-Tumoral Microenvironments Of Gastric Cancer

Introduction: Gastric cancers (GC) are one of the main causes of cancer-related deaths worldwide. Despite the dizzying progress in diagnostic and therapeutic strategies, many GC cases are diagnosed at advanced stages. Various signaling pathways have been identified to play vital roles in GC. Although the importance of these signaling pathways in GC has been demonstrated, further clinical studies are needed. Therefore, the expression of some signaling proteins in the tumoral and peri-tumoral microenvironments of GC are examined in this study. Methods: Protein expression levels were analyzed using Western blotting method in tumor and non-tumorous tissues from nine GC sufferers. The Kaplan-Meier method was used for the log-rank test to estimate survival curves and examine the survival distribution. Results: It was found that overexpression of c-MYC, mTOR, and AKT alongside decreased degrees of AMPK and TRAIL in GC tissues. Kaplan-Meier survival analysis highlighted worse survival outcomes in patients with high mTOR and AKT expression, while high TRAIL levels were associated with improved survival. Interestingly, a poorer prognosis was associated with higher c-MYC expression, highlighting the oncogenic role of this protein in GC through the AKT/mTOR pathway. On the other hand, decreased AMPK expression implied a lack of tumor-suppressive properties, most likely due to mTOR activation. Conclusion: These outcomes highlight the intricate interplay between GC's tumor-suppressive and carcinogenic mechanisms. Targeting these molecules by inhibiting mTOR or activating AMPK may provide new treatment approaches which can significantly increase TRAIL sensitivity. Moreover, further studies are necessary to confirm the present results and establish the integrated therapy approaches.