Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN ( = 8 × 10), THBS2 ( = 1.2 × 10), CTHRC1 ( = 1.1 × 10), SULF1 ( = 3.8 × 10), COL5A1 ( = 1.3 × 10), COL10A1 ( = 5.7 × 10), COL12A1 ( = 2 × 10) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (-value range 4.82 × 10-1.63 × 10). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.