Circulating microRNAs Capture Inflammatory and Muscle Wasting Phenotypes in Patients with Gastrointestinal Cancer

Background: Cancer cachexia (CC) is a multifactorial syndrome marked by systemic inflammation and skeletal muscle (SM) wasting. Circulating microRNAs (miRNAs) may regulate tumor–host interactions. This study investigated whether circulating miRNAs are associated with inflammatory cytokines, CC, and CT-derived SM mass in treatment-naïve patients with gastrointestinal cancer. Methods: Fifty-four newly diagnosed patients with gastrointestinal cancer and 15 controls were studied. CC was defined according to Fearon criteria. SM mass was assessed using the CT-derived L3 SM index. Plasma levels of miR-15b, -21, -29a, -29b, -133a, -206, and -486 were quantified by RT-qPCR. Serum concentrations of IL-6, IL-8, IL-10, and TNF-α were measured with a multiplex assay. Results: Compared to controls, patients had higher miR-15b (p = 0.003), miR-21 (p < 0.001), and miR-29b (p < 0.001), whereas miR-133a (p = 0.007), miR-206 (p = 0.022), and miR-486 (p = 0.001) were lower. Serum IL-6, IL-8, IL-10, and TNF-α were all elevated in patients vs controls (all p < 0.001). miR-29b was higher in cachectic vs non-cachectic patients (p = 0.003) and remained independently associated with CC (p = 0.007; OR = 10.926; 95% CI: 1.933–61.756). miR-133a was reduced in patients with low SM mass vs. controls (p = 0.007). miR-29b was higher in patients with low SM mass and CC vs. those with high SM mass without CC (p = 0.026). miR-133a (p = 0.004) and miR-206 (p = 0.002) were reduced in patients with low SM mass and CC vs. controls. Conclusions: Circulating miRNAs showed distinct associations with systemic inflammation, CC, and SM status in treatment-naïve gastrointestinal cancer. These findings support the concept that miRNA alterations reflect distinct biological dimensions of tumor–host interactions and warrant validation in larger longitudinal studies.