Association of Selected miRNAs (hsa-miR-27b, hsa-miR-128-3p, hsa-miR-145-5p, hsa-miR-552-3p) with HER2 Status and Chromosome 17 Centromere Copy Number Increase in Gastric Cancer.

Human epidermal growth factor receptor 2 (HER2) remains the most recognized and clinically established molecular biomarker in gastric cancer; however, the regulatory mechanisms underlying its dysregulation are not fully understood. This study aimed to identify microRNAs associated with HER2 gene amplification, chromosome 17 centromere copy number increase (CNI), or alternative mechanisms driving HER2 protein overexpression. We analyzed 115 gastric cancer patients treated surgically at a single institution, with available material for immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and microRNA profiling. Among 11 candidate microRNAs, four demonstrated significant associations with HER2-related alterations. hsa-miR-128-3p expression was positively associated with HER2 gene amplification, while hsa-miR-145-5p expression showed an inverse relationship with centromere enumeration probe 17 (CEP17) signal count and correlated with membranous HER2 protein expression. hsa-miR-27b-5p expression was linked to CEP17 CNI, whereas hsa-miR-552-3p expression was associated with both increased HER2 amplification and CEP17 signal count. Importantly, hsa-miR-27b-5p upregulation independently predicted worse overall survival, whereas hsa-miR-128-3p upregulation independently predicted improved survival outcomes. These findings identify distinct microRNA signatures associated with HER2 pathway alterations and prognosis in gastric cancer, highlighting their potential as biomarkers and contributors to HER2-driven tumor biology.