| 描述信息 |
Therapeutic targets for gastric cardia adenocarcinoma (GCA) often follow those of gastric cancer, with HER2 being a crucial target. Consequently, therapeutic targets specifically for GCA, particularly for HER2-negative patients, are lacking. Here, we conducted comprehensive omics profiling on 128 GCA patients using mass spectrometry, whole exome sequencing, RNA-Seq, and metabolic assays, and categorized patients into HER2-high, -low, and -negative groups based on HER2 levels. We identified HER2 as a robust prognostic marker for GCA patients, revealing DNA repair pathway enrichment in the HER2-high group and inflammatory features in the low and negative groups. Variations in genome instability were observed across HER2 subgroups, maintaining consistent tumor mutational burden. HER2-negative and low groups exhibited a tumor suppressive immune microenvironment, with an association between HER2 expression and distinct metabolic mechanisms. Our findings suggested PD-L2 and the CD47/SIRPA pair as potential targets for HER2-negative patients, offering insights to advance targeted therapy for GCA |
