A multicenter biomarker analysis in advanced esophageal squamous cell carcinoma highlighted how plasma lncRNA RIME could refine who benefits from first-line immunochemotherapy. The exploratory work reported that pretreatment plasma lncRNA RIME—especially when combined with PD-L1—distinguished patients with markedly different benefit outcomes after PD-1 inhibitor plus chemotherapy. The finding adds to a growing toolbox of RNA-based predictors intended to improve response rates and reduce unnecessary toxicity in immunotherapy-treated gastrointestinal cancers. The key practical question remains whether RIME’s performance is stable across assay platforms and treatment regimens. As the field moves toward more precise patient selection, further prospective validation and clinical utility analyses will determine whether RIME can become a decision-grade companion biomarker.