Stomach adenocarcinoma (STAD) is a common cancer with poor clinical outcomes globally. Due to a lack of early diagnostic markers of disease, the majority of patients are diagnosed at an advanced stage.

The aim of the present study is to provide some new insights into the available biomarkers for patients with STAD using bioinformatics.

RNA-Sequencing and other relevant data of patients with STAD from The Cancer Genome Atlas (TCGA) database were evaluated to identify differentially expressed genes (DEGs). Then, Machine Learning algorithms were undertaken to predict biomarkers. Additionally, Kaplan-Meier analysis was used to detect prognostic biomarkers. Furthermore, the Gene Ontology and Reactome pathways, protein-protein interactions (PPI), multiple sequence alignment, phylogenetic mapping, and correlation between clinical parameters were evaluated.

The results showed 61 DEGs, and the key dysregulated genes associated with STAD are MTHFD1L (Methylenetetrahydrofolate dehydrogenase 1-like), ZWILCH (Zwilch Kinetochore Protein), RCC2 (Regulator of chromosome condensation 2), DPT (Dermatopontin), GCOM1 (GRINL1A complex locus 1), and CLEC3B (C-Type Lectin Domain Family 3 Member B). Moreover, the survival analysis reported ASPA (Aspartoacylase) as a prognostic marker.

Our study provides a proof of concept of the potential value of ASPA as a prognostic factor in STAD, requiring further functional investigations to explore the value of emerging markers.