Abstract
Gastric cancer is one of the most common malignant tumors in the world. Alpha fetoprotein (AFP)-positive gastric cancer (AFPP-GC) is considered a special entity among gastric cancers. There is still controversy regarding the clinicopathological characteristics and prognosis of AFPP-GC, and the potential mechanism underlying its high malignant potential is still unclear. A comprehensive description of AFPP-GC genomic characteristics and regulatory mechanisms is lacking. This study analyzed the pathological characteristics and prognosis of AFPP-GC by utilizing clinical samples. The results showed that AFPP-GC has a poor prognosis and a high of risk liver metastasis. Tissue transcriptome sequencing showed that genes with high expression in AFPP-GC were involved in the activation of various cancer pathways, and genes with low expression were involved in the immune response. Single-sample gene set enrichment analysis showed that overexpression of AFP in AFPP-GC significantly inhibited the infiltration of CD8+ T cells. To further explore the genomic characteristics of AFPP-GC, the signaling pathway by which AFP regulates the invasion and metastasis of AFPP-GC cells was discussed. The results showed that AFPP-GC may promote cell invasion by regulating the PTEN/AKT1/SOX5/CES1 signaling axis. This study reveals the molecular mechanism underlying the increased malignant potential of AFPP-GC vs. AFP-negative gastric cancer (AFPN-GC). This provides important information for individualized treatment of AFPP-GC.